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la funci&#243;n inmunol&#243;gica y el ambiente&#46; En los &#250;ltimos a&#241;os ha ocurrido una aut&#233;ntica revoluci&#243;n en la investigaci&#243;n traslacional que ha permitido profundizar en el conocimiento de la patogenia de la DA y en el desarrollo de nuevas mol&#233;culas dirigidas a elementos clave de la inflamaci&#243;n&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">Este art&#237;culo revisa aquellos aspectos clave en la patogenia de la enfermedad con repercusi&#243;n en potenciales dianas terap&#233;uticas&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Patogenia</span><p id="par0020" class="elsevierStylePara elsevierViewall">La DA se ha considerado un modelo de disbalance entre las respuestas de los linfocitos T <span class="elsevierStyleItalic">helper</span> &#40;Th&#41; 1&#47;Th2&#44; con distorsi&#243;n hacia un predominio Th2&#46; Los linfocitos Th2 producen interleucina &#40;IL&#41;-4 e IL-13&#44; que inhiben la expresi&#243;n de filagrina&#44; circunstancia que permite establecer una relaci&#243;n entre la disfunci&#243;n inmunol&#243;gica y la alteraci&#243;n de la funci&#243;n de barrera caracter&#237;stica de la DA<a class="elsevierStyleCrossRef" href="#bib0330"><span class="elsevierStyleSup">4</span></a>&#46; En los &#250;ltimos a&#241;os&#44; diversos estudios traslacionales han centrado la patogenia de la DA en una respuesta Th2&#47;Th22 durante todo su curso&#44; con cierta participaci&#243;n de Th17&#44; y con una contribuci&#243;n adicional del eje Th1 en su etapa cr&#243;nica<a class="elsevierStyleCrossRef" href="#bib0335"><span class="elsevierStyleSup">5</span></a>&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">Sin embargo&#44; este esquema es una evidente simplificaci&#243;n&#44; y la mayor o menor contribuci&#243;n de estas respuestas variar&#225; entre los subtipos de la enfermedad&#46; En este sentido&#44; se han caracterizado al menos 3 fenotipos inmunol&#243;gicos de DA&#44; en los que destaca la contribuci&#243;n de la respuesta Th17&#44; a pesar de que mantienen una activaci&#243;n importante Th2&#47;Th22&#58; la DA pedi&#225;trica&#44; que muestra una mayor participaci&#243;n de la inmunidad innata&#44; IL-9 e IL-33&#59; la variante intr&#237;nseca &#40;20&#37; de los adultos&#41;&#44; que t&#237;picamente se presenta con niveles normales de IgE y sin antecedentes personales o familiares de atopia&#44; y&#44; por &#250;ltimo&#44; el fenotipo asi&#225;tico&#44; en el que predominan fenotipos con marcada liquenificaci&#243;n o psoriasiformes<a class="elsevierStyleCrossRefs" href="#bib0340"><span class="elsevierStyleSup">6&#8211;8</span></a>&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">Existen adem&#225;s otros potenciales actores relevantes en el proceso patog&#233;nico&#46; De este modo&#44; los queratinocitos son un elemento activo y producen citocinas&#44; como el <span class="elsevierStyleItalic">thymic stromal lymphopoietin</span> &#40;TSLP&#41; &#8212;capaz de inducir la expresi&#243;n de OX40L a trav&#233;s de la activaci&#243;n de las c&#233;lulas dendr&#237;ticas inmaduras&#8212; y la IL-33 &#8212;que induce la expresi&#243;n de OX40L a trav&#233;s de la activaci&#243;n de las c&#233;lulas linfoides innatas del grupo 2&#8212;&#44; que amplifican la respuesta Th2<a class="elsevierStyleCrossRef" href="#bib0355"><span class="elsevierStyleSup">9</span></a>&#46; Son las llamadas alarminas&#44; un elemento de inmunidad innata y un amplificador r&#225;pido y potente de la respuesta inflamatoria&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">Las IL-4&#47;13 est&#225;n implicadas en la s&#237;ntesis de IL-31&#44; clave en la inducci&#243;n del prurito&#44; y de IL-5&#44; que media el reclutamiento de Th2 y eosin&#243;filos&#46; Por otro lado&#44; el prurito lleva al rascado&#44; que facilita la disfunci&#243;n de la barrera cut&#225;nea y la colonizaci&#243;n por <span class="elsevierStyleItalic">Staphylococcus aureus</span>&#44; capaz de perpetuar la respuesta Th2 y la sobreexpresi&#243;n de IL-4&#44; IL-13 e IL-22&#46; Esta mayor colonizaci&#243;n est&#225; facilitada por la menor expresi&#243;n de p&#233;ptidos antimicrobianos en la piel lesional y aparentemente sana de los pacientes con DA&#44; tambi&#233;n relacionada con la v&#237;a IL-4&#47;13 &#40;<a class="elsevierStyleCrossRef" href="#fig0005">fig&#46; 1</a>&#41;<a class="elsevierStyleCrossRef" href="#bib0330"><span class="elsevierStyleSup">4</span></a>&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0040" class="elsevierStylePara elsevierViewall">Frente a la identificaci&#243;n de mol&#233;culas clave en la patogenia y&#44; por tanto&#44; potencialmente dianas terap&#233;uticas de anticuerpos monoclonales espec&#237;ficos&#44; se ha establecido la importancia de otras mol&#233;culas implicadas de forma transversal en el proceso inflamatorio&#46; En este apartado se ha estudiado la participaci&#243;n de la v&#237;a <span class="elsevierStyleItalic">Janus kinase&#47;signal transducer and activator of transcription</span> &#40;JAK-STAT&#41;&#44; activada por la IL-4&#44; en la desregulaci&#243;n inmune en la DA&#46; La familia de las JAK est&#225; formada por 4 miembros &#40;JAK1&#44; JAK2&#44; JAK3 y tirosina cinasa 2 &#91;TYK2&#93;&#41; y&#44; a diferencia de lo que ocurre en la alopecia areata o la psoriasis&#44; los 4 intervienen en la DA<a class="elsevierStyleCrossRef" href="#bib0360"><span class="elsevierStyleSup">10</span></a>&#46; Los distintos elementos de esta familia forman parte de los receptores citopl&#225;smicos de numerosas IL &#40;<a class="elsevierStyleCrossRef" href="#fig0010">fig&#46; 2</a>&#41;&#46; Su inhibici&#243;n tendr&#237;a&#44; por lo tanto&#44; un impacto en numerosas IL implicadas en la respuesta Th2 y la activaci&#243;n de los eosin&#243;filos<a class="elsevierStyleCrossRef" href="#bib0365"><span class="elsevierStyleSup">11</span></a>&#46;</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0045" class="elsevierStylePara elsevierViewall">El mayor conocimiento de las v&#237;as inflamatorias de la DA ha llevado al desarrollo de f&#225;rmacos dirigidos frente a distintas citocinas de forma espec&#237;fica&#44; as&#237; como en las v&#237;as del prurito&#44; y f&#225;rmacos de acci&#243;n amplia&#44; que intervienen sobre la se&#241;alizaci&#243;n intracelular&#44; afectando a la producci&#243;n final de diversas citocinas&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Tratamientos sist&#233;micos</span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">F&#225;rmacos biol&#243;gicos</span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Antagonismo de la respuesta celular Th2 &#40;IL-4 e IL-13&#41;</span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Bloqueo de la v&#237;a IL-4&#47;IL-13</span><p id="par0050" class="elsevierStylePara elsevierViewall">La IL-4 y la IL-13&#44; elementos clave de la respuesta Th2&#44; inician y dirigen la respuesta inmune en la DA&#44; de modo que el antagonismo espec&#237;fico frente a estas citocinas ha supuesto una revoluci&#243;n terap&#233;utica en esta enfermedad&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">Dupilumab es un anticuerpo monoclonal que inhibe la IL-4 y la IL-13 al bloquear la subunidad &#945; compartida en sus receptores &#40;IL-4R&#945;&#41;&#46; En 2 ensayos cl&#237;nicos &#40;EC&#41; fase <span class="elsevierStyleSmallCaps">iii</span> &#40;SOLO-1 y SOLO-2&#41;&#44; de dise&#241;o id&#233;ntico&#44; en un total de 1&#46;379 pacientes adultos con DA moderada a grave&#44; la administraci&#243;n de dupilumab 300<span class="elsevierStyleHsp" style=""></span>mg cada 2 semanas durante 16 semanas fue superior a placebo en el objetivo primario &#40;IGA de 0 o 1&#58; 38 y 36&#37; para dupilumab vs&#46; 10 y 8&#37; para placebo&#44; respectivamente&#41;<a class="elsevierStyleCrossRef" href="#bib0370"><span class="elsevierStyleSup">12</span></a>&#46; Tambi&#233;n fue superior para todos los objetivos secundarios &#40;EASI-75&#44; reducci&#243;n del prurito&#44; s&#237;ntomas de ansiedad y depresi&#243;n&#44; calidad de vida y necesidad de medicaci&#243;n de rescate&#41; en comparaci&#243;n con placebo<a class="elsevierStyleCrossRefs" href="#bib0370"><span class="elsevierStyleSup">12&#44;13</span></a>&#46; Otro EC fase <span class="elsevierStyleSmallCaps">iii</span> ha demostrado tambi&#233;n resultados positivos de dupilumab en combinaci&#243;n con corticoides t&#243;picos frente a placebo tras un a&#241;o de tratamiento &#40;EASI-75&#58; 65&#37; para dupilumab 300<span class="elsevierStyleHsp" style=""></span>mg cada 2 semanas vs&#46; 22&#37; para placebo&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;0001&#41;<a class="elsevierStyleCrossRef" href="#bib0380"><span class="elsevierStyleSup">14</span></a>&#46; Dos metaan&#225;lisis recientes muestran una eficacia superior a placebo&#44; con beneficios similares para las pautas de 300<span class="elsevierStyleHsp" style=""></span>mg semanales o cada 2 semanas&#46; Los principales efectos adversos espec&#237;ficos son las reacciones a la inyecci&#243;n local del f&#225;rmaco y la conjuntivitis<a class="elsevierStyleCrossRefs" href="#bib0385"><span class="elsevierStyleSup">15&#44;16</span></a>&#46; En este momento se encuentran en su etapa final 2 EC fase <span class="elsevierStyleSmallCaps">iii</span> en edad pedi&#225;trica<a class="elsevierStyleCrossRefs" href="#bib0395"><span class="elsevierStyleSup">17&#44;18</span></a>&#46; En marzo de este a&#241;o&#44; la FDA ha extendido la aprobaci&#243;n de dupilumab a poblaci&#243;n adolescente de entre 12 y 17 a&#241;os&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall">Tralokinumab es un anticuerpo monoclonal dirigido frente a la IL-13&#46; Bloquea de forma competitiva la uni&#243;n a 2 receptores distintos&#58; el receptor heterodim&#233;rico&#44; compuesto por IL-4R&#945; &#40;antagonizado por dupilumab&#41; e IL-13R&#945;1&#44; y el receptor se&#241;uelo IL-13R&#945;2&#44; que media la regulaci&#243;n end&#243;gena de IL-13&#46; Esta v&#237;a permite evaluar&#44; por lo tanto&#44; en qu&#233; medida la inhibici&#243;n de IL-4 puede ser redundante con respecto a IL-13 en la patog&#233;nesis de la enfermedad<a class="elsevierStyleCrossRef" href="#bib0405"><span class="elsevierStyleSup">19</span></a>&#46; En un EC fase <span class="elsevierStyleSmallCaps">ii</span>b con 204 pacientes adultos con DA moderada a grave&#44; la administraci&#243;n de tralokinumab a dosis de 300<span class="elsevierStyleHsp" style=""></span>mg cada 2 semanas durante 12 semanas logr&#243; una reducci&#243;n del EASI frente a placebo &#40;media de cambio ajustada respecto al valor basal de &#8722;15&#44;7 vs&#46; &#8722;10&#44;8&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;011&#41; y un mayor porcentaje de pacientes present&#243; un IGA 0-1 &#40;26&#44;7 vs&#46; 11&#44;8&#37;&#41;&#46; Estos resultados muestran tambi&#233;n una alta respuesta a placebo&#44; probablemente debido al uso concomitante de corticoides t&#243;picos en este EC&#46; Tambi&#233;n hubo una mejor&#237;a significativa en el SCORAD&#44; el <span class="elsevierStyleItalic">Dermatology Life Quality Index</span> y el prurito<a class="elsevierStyleCrossRef" href="#bib0410"><span class="elsevierStyleSup">20</span></a>&#46; En este momento est&#225;n en marcha EC de fase <span class="elsevierStyleSmallCaps">iii</span> de tralokinumab en adultos<a class="elsevierStyleCrossRef" href="#bib0415"><span class="elsevierStyleSup">21</span></a> y adolescentes<a class="elsevierStyleCrossRef" href="#bib0420"><span class="elsevierStyleSup">22</span></a>&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">Lebrikizumab es otro anticuerpo monoclonal dirigido frente a la IL-13&#46; Se une a la IL-13 soluble e inhibe su uni&#243;n al IL-4R&#945;<a class="elsevierStyleCrossRef" href="#bib0425"><span class="elsevierStyleSup">23</span></a>&#46; En un EC fase <span class="elsevierStyleSmallCaps">ii</span> en 209 pacientes adultos con DA moderada a grave&#44; el grupo tratado con lebrikizumab 125<span class="elsevierStyleHsp" style=""></span>mg cada 4 semanas present&#243; un mayor porcentaje de EASI-50 que el grupo tratado con placebo &#40;82&#44;4 vs&#46; 62&#44;3&#37;&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;026&#41;&#46; De nuevo&#44; hubo respuestas no despreciables en el grupo placebo&#44; que podr&#237;an atribuirse al uso concomitante de corticoides t&#243;picos<a class="elsevierStyleCrossRef" href="#bib0430"><span class="elsevierStyleSup">24</span></a>&#46; En este momento se encuentra activo un ensayo que eval&#250;a su eficacia a dosis de 250<span class="elsevierStyleHsp" style=""></span>mg cada 2 y 4 semanas<a class="elsevierStyleCrossRef" href="#bib0435"><span class="elsevierStyleSup">25</span></a>&#46;</p><p id="par0070" class="elsevierStylePara elsevierViewall">El bloqueo espec&#237;fico de la IL-13 tambi&#233;n ha sido evaluado en el asma&#44; con mejor&#237;as modestas para tralokinumab y lebrikizumab<a class="elsevierStyleCrossRefs" href="#bib0440"><span class="elsevierStyleSup">26&#44;27</span></a>&#46; Al igual que en la DA&#44; la respuesta podr&#237;a ser mayor en aquellos pacientes con concentraciones m&#225;s elevadas de marcadores relacionados con la IL-13<a class="elsevierStyleCrossRef" href="#bib0410"><span class="elsevierStyleSup">20</span></a>&#46; Sin embargo&#44; se necesitan EC en monoterapia para evaluar la utilidad del bloqueo exclusivo de IL-13&#46;</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Bloqueo de la inducci&#243;n a la respuesta Th2&#58; TSLP&#44; OX40L e IL-33</span><p id="par0075" class="elsevierStylePara elsevierViewall">El eje Th2 tambi&#233;n incluye la v&#237;a de la TSLP&#44; clave en la interacci&#243;n entre la epidermis y la activaci&#243;n inmune innata y adaptativa&#44; al derivar la respuesta inflamatoria a un fenotipo al&#233;rgico a trav&#233;s de la activaci&#243;n de las c&#233;lulas dendr&#237;ticas inmaduras&#44; que expresan OX40L&#44; lo que permite la polarizaci&#243;n hacia una respuesta Th2<a class="elsevierStyleCrossRef" href="#bib0450"><span class="elsevierStyleSup">28</span></a>&#46; De forma parecida&#44; IL-33&#44; producida por las c&#233;lulas epiteliales&#44; puede regular positivamente el eje TSLP-c&#233;lula dendr&#237;tica-OX40L&#44; participando en la inducci&#243;n y el mantenimiento de la respuesta Th2<a class="elsevierStyleCrossRefs" href="#bib0455"><span class="elsevierStyleSup">29&#44;30</span></a>&#46; La inhibici&#243;n de esta v&#237;a podr&#237;a ser interesante desde el punto de vista del tratamiento temprano&#44; debido a su participaci&#243;n en el inicio de la respuesta Th2&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">Tezepelumab es un anticuerpo monoclonal frente a TSLP&#44; recientemente evaluado en un EC fase <span class="elsevierStyleSmallCaps">ii</span>a&#44; sin presentar una eficacia superior a placebo a las 16 semanas<a class="elsevierStyleCrossRef" href="#bib0465"><span class="elsevierStyleSup">31</span></a>&#46; En este momento se encuentra en marcha otro EC de b&#250;squeda de dosis con tezepelumab &#40;NCT03809663&#41;&#46; Otra mol&#233;cula&#44; la MK-8226&#44; antagonista del receptor del TSLP&#44; fue evaluada en un EC fase <span class="elsevierStyleSmallCaps">i</span> a distintas dosis&#44; por v&#237;a IV&#44; con resultados que muestran un descenso significativo del EASI a dosis de 3<span class="elsevierStyleHsp" style=""></span>mg&#47;kg en comparaci&#243;n con placebo a las 12 semanas &#40;10&#44;20 vs&#46; 0&#44;38&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;015&#41;<a class="elsevierStyleCrossRef" href="#bib0470"><span class="elsevierStyleSup">32</span></a>&#46;</p><p id="par0085" class="elsevierStylePara elsevierViewall">Un anticuerpo monoclonal frente a OX40&#44; el GBR 830&#44; ha sido evaluado frente a placebo a dosis de 10<span class="elsevierStyleHsp" style=""></span>mg&#47;kg&#47;4<span class="elsevierStyleHsp" style=""></span>s IV durante 2 meses&#44; con resultados positivos<a class="elsevierStyleCrossRef" href="#bib0475"><span class="elsevierStyleSup">33</span></a>&#46; En este momento est&#225;n en marcha EC con otro inhibidor del OX40&#44; la mol&#233;cula KHK4093 &#40;NCT03096223 y NCT03703102&#41;&#44; as&#237; como con etokimab&#47;ANB020&#44; un anticuerpo monoclonal anti-IL-33 &#40;NCT03533751&#41;&#46;</p></span></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Antagonismo de la respuesta celular Th22</span><p id="par0090" class="elsevierStylePara elsevierViewall">Los linfocitos Th22 son los principales productores de IL-22 y participan tanto en las formas agudas como cr&#243;nicas de la DA&#46; La IL-22 puede aumentar la disfunci&#243;n de barrera&#44; inducir hiperplasia epid&#233;rmica e inhibir prote&#237;nas clave en la queratinizaci&#243;n normal&#44; como la filagrina<a class="elsevierStyleCrossRef" href="#bib0480"><span class="elsevierStyleSup">34</span></a>&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">En un EC fase <span class="elsevierStyleSmallCaps">ii</span>a&#44; el uso de fezakinumab &#40;ILV-094&#41;&#44; un anti-IL-22&#44; a dosis de 300<span class="elsevierStyleHsp" style=""></span>mg cada 2 semanas&#44; consigui&#243; una mejor&#237;a&#44; aunque no significativa frente a placebo en la disminuci&#243;n del SCORAD en pacientes con DA moderada a grave&#46; El suban&#225;lisis de pacientes con DA grave s&#237; mostr&#243; diferencias significativas en la reducci&#243;n del <span class="elsevierStyleItalic">Body Surface Area</span> &#40;BSA&#41; y el IGA<a class="elsevierStyleCrossRef" href="#bib0485"><span class="elsevierStyleSup">35</span></a>&#46; El beneficio de este f&#225;rmaco podr&#237;a estar limitado a pacientes con peor respuesta al bloqueo de la v&#237;a Th2 y con mayor expresi&#243;n de Th22<a class="elsevierStyleCrossRef" href="#bib0490"><span class="elsevierStyleSup">36</span></a>&#44; aunque la evidencia hasta la fecha es limitada&#46;</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Antagonismo de la respuesta celular Th17</span><p id="par0100" class="elsevierStylePara elsevierViewall">Como se ha mencionado&#44; en la etapa cr&#243;nica de la DA y en determinados grupos de pacientes se mantiene una respuesta Th2 y Th22&#44; pero existe una activaci&#243;n paralela del eje Th1&#47;Th17<a class="elsevierStyleCrossRef" href="#bib0495"><span class="elsevierStyleSup">37</span></a>&#46; Recientemente&#44; se ha estudiado el bloqueo de la IL-17A y la IL-17C&#46; Aunque los datos sobre la inhibici&#243;n de este eje en la DA son a&#250;n muy preliminares&#44; resulta interesante su desarrollo&#44; dado el potencial terap&#233;utico en determinados subfenotipos de DA&#46;</p><p id="par0105" class="elsevierStylePara elsevierViewall">Secukinumab&#44; un inhibidor selectivo de la IL-17A&#44; aprobado en la psoriasis&#44; ha sido evaluado recientemente en un EC de fase <span class="elsevierStyleSmallCaps">ii</span> en la DA &#40;NCT02594098&#41;&#44; con la pauta de inducci&#243;n empleada en la psoriasis y con un mantenimiento a dosis de 300<span class="elsevierStyleHsp" style=""></span>mg&#47;4 semanas o intensificado 300<span class="elsevierStyleHsp" style=""></span>mg&#47;2 semanas&#46; Los resultados se encuentran pendientes de publicaci&#243;n<a class="elsevierStyleCrossRef" href="#bib0500"><span class="elsevierStyleSup">38</span></a>&#46;</p><p id="par0110" class="elsevierStylePara elsevierViewall">Por otro lado&#44; est&#225;n en marcha estudios &#40;NCT03568071&#44; NCT03689829&#44; NCT03864627&#41; con un anticuerpo dirigido frente a la IL-17C&#44; MOR106&#44; que podr&#237;a mediar una disminuci&#243;n en los niveles de IgE y citocinas Th2<a class="elsevierStyleCrossRef" href="#bib0505"><span class="elsevierStyleSup">39</span></a>&#46;</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Bloqueo de la v&#237;a IL-31 y OSMR&#946; &#40;se&#241;alizaci&#243;n del prurito&#41;</span><p id="par0115" class="elsevierStylePara elsevierViewall">La IL-31 es una citocina producida principalmente por los linfocitos Th2&#44; muy relacionada con el prurito&#44; en distintos tipos celulares&#44; incluyendo las neuronas perif&#233;ricas<a class="elsevierStyleCrossRefs" href="#bib0510"><span class="elsevierStyleSup">40&#44;41</span></a>&#46; La IL-31 se une a un receptor heterodim&#233;rico compuesto por el receptor &#945; de la IL-31 &#40;IL-31R&#945;&#41; y el receptor &#946; de oncastatina M &#40;OSMR&#946;&#41;&#46; Su bloqueo&#44; por tanto&#44; podr&#237;a tambi&#233;n romper el c&#237;rculo vicioso de prurito-rascado y el compromiso de la funci&#243;n de barrera epid&#233;rmica&#46;</p><p id="par0120" class="elsevierStylePara elsevierViewall">Nemolizumab bloquea el receptor &#945; de la IL-31 &#40;IL-31R&#945;&#41;&#46; Hasta la fecha&#44; un EC fase <span class="elsevierStyleSmallCaps">ii</span> controlado con placebo en adultos tratados con nemolizumab &#40;dosis de 0&#44;1<span class="elsevierStyleHsp" style=""></span>mg&#47;kg&#44; 0&#44;5<span class="elsevierStyleHsp" style=""></span>mg&#47;kg o 2<span class="elsevierStyleHsp" style=""></span>mg&#47;kg cada 4 semanas durante 12 semanas&#41; ha demostrado reducciones del prurito&#59; sin embargo&#44; la mejor&#237;a en escalas cl&#237;nicas no alcanz&#243; la significaci&#243;n estad&#237;stica<a class="elsevierStyleCrossRefs" href="#bib0510"><span class="elsevierStyleSup">40&#44;42</span></a>&#46; Nemolizumab podr&#237;a ser efectivo en la reducci&#243;n del prurito&#44; as&#237; como en la actividad cotidiana y la productividad laboral<a class="elsevierStyleCrossRef" href="#bib0525"><span class="elsevierStyleSup">43</span></a>&#44; con un perfil de seguridad adecuado&#46; En este momento est&#225; pendiente la finalizaci&#243;n de un EC de b&#250;squeda de dosis &#40;NCT03100344&#41;&#46;</p><p id="par0125" class="elsevierStylePara elsevierViewall">El EC fase <span class="elsevierStyleSmallCaps">i</span> &#40;NCT01614756&#41; que investigaba el uso de un anti-IL-31 &#40;BMS-981164&#41; finaliz&#243; en una etapa temprana y no se han publicado los resultados&#46; A&#250;n se desconoce&#44; por tanto&#44; si los efectos del bloqueo sobre la IL-31 ser&#237;an solo sintom&#225;ticos sobre el prurito&#44; dado que estos no se han asociado a mejoras significativas en los &#237;ndices de inflamaci&#243;n cut&#225;nea&#46;</p><p id="par0130" class="elsevierStylePara elsevierViewall">Por otro lado&#44; se ha realizado un EC fase <span class="elsevierStyleSmallCaps">i</span>a&#47;<span class="elsevierStyleSmallCaps">i</span>b con KPL-716&#44; un anticuerpo anti-OSMR&#946; que ha demostrado una mejor&#237;a del EASI y en las escalas de prurito comparado con placebo<a class="elsevierStyleCrossRef" href="#bib0530"><span class="elsevierStyleSup">44</span></a>&#46;</p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Antagonismo de la IgE</span><p id="par0135" class="elsevierStylePara elsevierViewall">Omalizumab&#44; un anti-IgE&#44; aprobado en el tratamiento del asma&#44; ha sido evaluado en un metaan&#225;lisis&#44; sin evidencia de efectividad global en adultos con DA<a class="elsevierStyleCrossRef" href="#bib0535"><span class="elsevierStyleSup">45</span></a>&#46; Est&#225; en investigaci&#243;n su uso en poblaci&#243;n pedi&#225;trica &#40;NCT02300701&#41;&#46;</p></span></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Mol&#233;culas peque&#241;as</span><p id="par0140" class="elsevierStylePara elsevierViewall">Se incluyen agentes de administraci&#243;n oral que generan una reducci&#243;n amplia&#44; menos espec&#237;fica&#44; de la liberaci&#243;n de mediadores&#46; Esta estrategia tiene ventajas en la DA&#44; ya que&#44; a diferencia de la psoriasis&#44; no existe evidencia de la implicaci&#243;n fundamental de una mol&#233;cula clave en la patog&#233;nesis de la enfermedad&#46; Por el contrario&#44; esta menor especificidad podr&#237;a relacionarse con potenciales problemas de seguridad&#46;</p><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Inhibici&#243;n de la v&#237;a de se&#241;alizaci&#243;n JAK-STAT</span><p id="par0145" class="elsevierStylePara elsevierViewall">En este momento existen 4 inhibidores de JAK por v&#237;a oral en estudio<a class="elsevierStyleCrossRef" href="#bib0365"><span class="elsevierStyleSup">11</span></a>&#46; Baricitinib antagoniza a JAK 1 &#40;asociada con la modulaci&#243;n de las citocinas IL-4&#44; IL-6&#44; IL-10&#44; IL-13&#44; IL-31 e IFN-&#947;&#41; y JAK2 &#40;que modula las citocinas IL-5&#44; IL-6&#44; IL-23&#44; IL-31 e IFN-&#947;&#41;<a class="elsevierStyleCrossRefs" href="#bib0365"><span class="elsevierStyleSup">11&#44;46</span></a>&#46; En el primer EC fase <span class="elsevierStyleSmallCaps">ii</span> la administraci&#243;n de baricitinib&#44; a dosis de 4<span class="elsevierStyleHsp" style=""></span>mg una vez al d&#237;a por v&#237;a oral&#44; en pacientes con DA moderada a grave&#44; se asoci&#243; a una mayor consecuci&#243;n de EASI-50 en comparaci&#243;n con placebo &#40;61 vs&#46; 37&#37;&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;027&#41; a las 16 semanas&#44; con buena tolerancia&#46; Entre los efectos adversos reportados se encuentra la elevaci&#243;n asintom&#225;tica de la creatina cinasa&#44; pero no hubo casos de eventos tromb&#243;ticos ni de herpes z&#243;ster<a class="elsevierStyleCrossRef" href="#bib0545"><span class="elsevierStyleSup">47</span></a>&#46;</p><p id="par0150" class="elsevierStylePara elsevierViewall">Upadacitinib &#40;ABT-494&#41; y abrocitinib &#40;PF-04965842&#41; son inhibidores selectivos de JAK1&#44; de los que se dispone de resultados iniciales prometedores&#46; Un EC fase <span class="elsevierStyleSmallCaps">ii</span>b evalu&#243; el uso de upadacitinib a dosis de 7&#44;5&#47;15&#47;30<span class="elsevierStyleHsp" style=""></span>mg frente a placebo durante 16 semanas&#46; La reducci&#243;n en el EASI frente al valor basal fue del 74&#47;62&#47;39&#37; para las dosis de 30&#47;15&#47;7&#44;5<span class="elsevierStyleHsp" style=""></span>mg&#44; respectivamente&#44; mejor&#237;as que podr&#237;an ser similares a las obtenidas con dupilumab&#46; En este momento se encuentra activo un EC fase <span class="elsevierStyleSmallCaps">iii</span> de evaluaci&#243;n de la eficacia de upadacitinib en adultos y adolescentes &#40;NCT03607422&#41;&#46; Otro EC fase <span class="elsevierStyleSmallCaps">ii</span>b evalu&#243; el uso de abrocitinib a dosis de 10&#47;30&#47;100&#47;200<span class="elsevierStyleHsp" style=""></span>mg al d&#237;a frente a placebo&#44; con reducciones del EASI que solo fueron significativas para las dosis de 200<span class="elsevierStyleHsp" style=""></span>mg &#40;82&#44;6&#37;&#59; p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#41; y de 100<span class="elsevierStyleHsp" style=""></span>mg &#40;59&#37;&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;009&#41; frente a placebo &#40;35&#44;2&#37;&#41;<a class="elsevierStyleCrossRef" href="#bib0540"><span class="elsevierStyleSup">46</span></a>&#46; Est&#225;n en marcha numerosos EC fase <span class="elsevierStyleSmallCaps">iii</span> de abrocitinib a dosis de 100 y 200<span class="elsevierStyleHsp" style=""></span>mg frente a placebo &#40;NCT03349060&#44; NCT03575871&#44; NCT03627767 y NCT03422822&#41;&#44; as&#237; como un EC fase <span class="elsevierStyleSmallCaps">iii</span> comparado con dupilumab &#40;NCT03720470&#41;&#46; Por &#250;ltimo&#44; ASN002 es un inhibidor dual de las v&#237;as JAK y SYK&#46; La inhibici&#243;n PAN-JAK afecta a la se&#241;alizaci&#243;n de diversas citocinas en la DA &#40;IL-4&#44; IL-13&#44; IL-31 e IL-33&#41;&#44; mientras que la inhibici&#243;n de SYK suprime la se&#241;alizaci&#243;n de citocinas proinflamatorias &#40;IL-1&#946;&#44; IL-10&#44; IL-17&#41;&#46; En el primer EC de fase <span class="elsevierStyleSmallCaps">i</span>b de ASNN002&#44; el porcentaje de pacientes que alcanz&#243; un EASI-50 a los 28 d&#237;as fue superior a placebo para las dosis de 40 y 80<span class="elsevierStyleHsp" style=""></span>mg<a class="elsevierStyleCrossRef" href="#bib0550"><span class="elsevierStyleSup">48</span></a>&#46;</p><p id="par0155" class="elsevierStylePara elsevierViewall">En la actualidad&#44; est&#225;n activos EC de fase <span class="elsevierStyleSmallCaps">iii</span> con estos 4 f&#225;rmacos&#46;</p></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Antagonismo de la fosfodiesterasa 4</span><p id="par0160" class="elsevierStylePara elsevierViewall">Recientemente&#44; se ha evaluado el tratamiento con inhibidores de la fosfodiesterasa &#40;PDE4&#41;&#44; de administraci&#243;n t&#243;pica y oral&#46; En la DA la actividad de la PDE4 en distintas c&#233;lulas inflamatorias est&#225; aumentada en comparaci&#243;n con la piel sana&#46; La PDE degrada el AMPc&#44; que normalmente inhibe la producci&#243;n de diversas citocinas proinflamatorias&#44; como la IL-4&#44; la IL-31 y la PGE-2&#46; El antagonismo de la PDE4 act&#250;a de forma amplia y no espec&#237;fica&#44; ya que eleva el AMPc intracelular y permite reducir la liberaci&#243;n de citocinas y quimiocinas<a class="elsevierStyleCrossRef" href="#bib0555"><span class="elsevierStyleSup">49</span></a>&#46;</p><p id="par0165" class="elsevierStylePara elsevierViewall">En un estudio fase <span class="elsevierStyleSmallCaps">ii</span>&#44; apremilast 40<span class="elsevierStyleHsp" style=""></span>mg&#47;12<span class="elsevierStyleHsp" style=""></span>h logr&#243; una reducci&#243;n del EASI superior a placebo &#40;31&#44;57 vs&#46; 10&#44;98&#37;&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;034&#41;&#46; Sin embargo&#44; no hubo diferencias estad&#237;sticamente significativas en el EASI-50 ni en el prurito<a class="elsevierStyleCrossRef" href="#bib0560"><span class="elsevierStyleSup">50</span></a>&#46; En este momento no hay nuevos EC con apremilast en DA&#46;</p></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Antagonismo del receptor de la histamina 4</span><p id="par0170" class="elsevierStylePara elsevierViewall">En los &#250;ltimos a&#241;os se ha estudiado el papel del antagonismo del receptor de la histamina 4&#44; que no solo lograr&#237;a un efecto antipruriginoso&#44; sino tambi&#233;n antiinflamatorio&#44; dado que la activaci&#243;n del receptor en el queratinocito interfiere en su proliferaci&#243;n y en la funci&#243;n de barrera<a class="elsevierStyleCrossRef" href="#bib0565"><span class="elsevierStyleSup">51</span></a>&#46;</p><p id="par0175" class="elsevierStylePara elsevierViewall">Un EC fase <span class="elsevierStyleSmallCaps">ii</span>a con un antagonista del receptor de la histamina 4&#44; JNJ-39758979&#44; mostr&#243; diferencias significativas en la reducci&#243;n del prurito&#44; no as&#237; del EASI&#46; Sin embargo&#44; este EC fue interrumpido debido a 2 casos de neutropenia grave<a class="elsevierStyleCrossRef" href="#bib0570"><span class="elsevierStyleSup">52</span></a>&#46; Recientemente se han publicado los resultados de EC en fase <span class="elsevierStyleSmallCaps">ii</span> con otro antagonista del receptor de la histamina 4&#44; ZPL-3893787&#44; con disminuciones significativas frente a placebo del EASI y&#44; en cambio&#44; no significativas en el prurito<a class="elsevierStyleCrossRef" href="#bib0575"><span class="elsevierStyleSup">53</span></a>&#46;</p></span><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Bloqueo del receptor de la neuroquinina 1</span><p id="par0180" class="elsevierStylePara elsevierViewall">La sustancia P&#44; mediadora del prurito&#44; se une principalmente al receptor de la neuroquinina 1&#44; que se expresa tanto en el sistema nervioso central como en la piel&#46; En este sentido&#44; antagonistas del receptor de la neuroquinina 1 de administraci&#243;n oral&#44; como aprepitant&#44; podr&#237;an mejorar el prurito<a class="elsevierStyleCrossRef" href="#bib0580"><span class="elsevierStyleSup">54</span></a>&#46; Sin embargo&#44; su uso en la DA no parece aportar beneficios<a class="elsevierStyleCrossRef" href="#bib0585"><span class="elsevierStyleSup">55</span></a>&#46; Otros inhibidores del receptor de la neuroquinina 1&#44; tradipitant y serlopitant&#44; est&#225;n siendo evaluados&#44; aunque tambi&#233;n con resultados modestos&#46;</p><p id="par0185" class="elsevierStylePara elsevierViewall">En la <a class="elsevierStyleCrossRef" href="#tbl0005">tabla 1</a> se resumen los principales EC de los nuevos f&#225;rmacos sist&#233;micos&#44; y en las <a class="elsevierStyleCrossRefs" href="#fig0005">figuras 1 y 2</a> se se&#241;alan sus dianas terap&#233;uticas&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia></span></span><span id="sec0085" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Tratamientos t&#243;picos</span><p id="par0190" class="elsevierStylePara elsevierViewall">De forma independiente a los avances en los f&#225;rmacos sist&#233;micos&#44; las terapias t&#243;picas siguen siendo esenciales tanto en la reparaci&#243;n de la funci&#243;n de barrera como en el transporte de mol&#233;culas antiinflamatorias&#46; M&#225;s all&#225; de los emolientes&#44; los corticoides y los inhibidores de la calcineurina&#44; se han desarrollado nuevas mol&#233;culas de peque&#241;o tama&#241;o que permiten considerar su uso t&#243;pico&#46;</p><span id="sec0090" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Inhibidores t&#243;picos de la se&#241;alizaci&#243;n JAK&#47;STAT</span><p id="par0195" class="elsevierStylePara elsevierViewall">En el momento actual se encuentran en investigaci&#243;n inhibidores t&#243;picos de la v&#237;a JAK&#47;STAT&#46; Entre estos&#44; tofacitinib t&#243;pico al 2&#37; y ruxolitinib al 1&#44;5&#37; parecen tener eficacia en la reducci&#243;n del EASI y del prurito<a class="elsevierStyleCrossRef" href="#bib0540"><span class="elsevierStyleSup">46</span></a>&#46; En un EC japon&#233;s&#44; delgocitinib&#44; un inhibidor PAN-JAK&#44; tambi&#233;n ha demostrado mejor&#237;as del EASI superiores al veh&#237;culo&#44; sin efectos adversos significativos<a class="elsevierStyleCrossRef" href="#bib0590"><span class="elsevierStyleSup">56</span></a>&#46;</p></span><span id="sec0095" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Inhibidores t&#243;picos de la PDE4</span><p id="par0200" class="elsevierStylePara elsevierViewall">El crisaborol t&#243;pico al 2&#37; es el primer inhibidor de la PDE4 aprobado en adultos y ni&#241;os mayores de 2 a&#241;os con DA leve a moderada&#46; En los EC de fase <span class="elsevierStyleSmallCaps">iii</span> se demostr&#243; una eficacia estad&#237;sticamente significativa en t&#233;rminos de IGA-0 &#40;51&#44;7&#37;&#41; e IGA-1 &#40;48&#44;5&#37;&#41; frente a veh&#237;culo &#40;40&#44;6 y 29&#44;7&#37;&#44; respectivamente&#41; a las 4 semanas<a class="elsevierStyleCrossRef" href="#bib0595"><span class="elsevierStyleSup">57</span></a>&#46; Se han descrito reacciones adversas leves&#44; como dolor o quemaz&#243;n en el lugar de aplicaci&#243;n&#46; Est&#225;n en marcha EC con otros inhibidores de la PDE4&#44; como las mol&#233;culas E6005 y AN2898<a class="elsevierStyleCrossRef" href="#bib0600"><span class="elsevierStyleSup">58</span></a>&#46;</p></span><span id="sec0100" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Ominagan</span><p id="par0205" class="elsevierStylePara elsevierViewall">La menor producci&#243;n de p&#233;ptidos antimicrobianos en la DA facilita la colonizaci&#243;n y la infecci&#243;n microbiana e incrementa la respuesta inflamatoria&#46; En este sentido&#44; se ha desarrollado ominagan en gel&#44; un p&#233;ptido antimicrobiano evaluado en 2 EC fase <span class="elsevierStyleSmallCaps">ii</span>&#59; aunque se desconocen sus resultados&#44; existen publicaciones que indican buena tolerancia<a class="elsevierStyleCrossRef" href="#bib0605"><span class="elsevierStyleSup">59</span></a>&#46;</p></span><span id="sec0105" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0130">Tapinarof</span><p id="par0210" class="elsevierStylePara elsevierViewall">Tapinarof es un antiinflamatorio no esteroideo que act&#250;a como agonista del receptor de hidrocarburo arilo&#44; pudiendo mejorar la funci&#243;n de barrera y limitar la respuesta Th2<a class="elsevierStyleCrossRef" href="#bib0610"><span class="elsevierStyleSup">60</span></a>&#46; En un EC fase <span class="elsevierStyleSmallCaps">ii</span> el uso de tapinarof al 1&#37; 2 veces al d&#237;a demostr&#243; diferencias significativas en el IGA 0-1 y en la reducci&#243;n del EASI&#44; el SCORAD y el BSA frente al veh&#237;culo&#44; con buena tolerancia y desarrollo de 2 casos de dermatitis de contacto sobre 165 pacientes tratados<a class="elsevierStyleCrossRef" href="#bib0615"><span class="elsevierStyleSup">61</span></a>&#46;</p></span><span id="sec0110" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0135">PR022 &#40;&#225;cido hipocloroso&#41;</span><p id="par0215" class="elsevierStylePara elsevierViewall">En una serie de casos de pacientes con DA&#44; el uso al 0&#44;008 y 0&#44;002&#37; de &#225;cido hipocloroso t&#243;pico&#44; en hidrogel&#44; se asoci&#243; a una reducci&#243;n del prurito&#46; Se cree que el &#225;cido hipocloroso podr&#237;a disminuir las concentraciones de distintas citocinas&#44; como el TNF-&#945;&#44; la IL-2&#44; el IFN-&#947; o la histamina<a class="elsevierStyleCrossRef" href="#bib0605"><span class="elsevierStyleSup">59</span></a>&#46; Est&#225; en marcha un EC fase <span class="elsevierStyleSmallCaps">ii</span> en adultos con DA leve-moderada &#40;NCT03351777&#41;&#46;</p></span><span id="sec0115" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0140">SP14019&#47;Cyclatop</span><p id="par0220" class="elsevierStylePara elsevierViewall">SP14019&#47;Cyclatop es una formulaci&#243;n t&#243;pica en espray de ciclosporina al 5&#37;&#44; evaluada en un EC fase <span class="elsevierStyleSmallCaps">ii</span> en pacientes<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>2 a&#241;os &#40;NCT02865356&#41;&#46; Sus resultados fueron presentados en el congreso europeo de dermatolog&#237;a del 2018&#44; con mejor&#237;as significativas del EASI y el IGA frente al veh&#237;culo a las 4 semanas&#44; con buena tolerancia y escasa absorci&#243;n sist&#233;mica<a class="elsevierStyleCrossRef" href="#bib0620"><span class="elsevierStyleSup">62</span></a>&#46;</p><p id="par0225" class="elsevierStylePara elsevierViewall">En la <a class="elsevierStyleCrossRef" href="#tbl0010">tabla 2</a> se resumen los f&#225;rmacos t&#243;picos en v&#237;as de investigaci&#243;n&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia></span></span></span><span id="sec0120" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0145">Conclusiones</span><p id="par0230" class="elsevierStylePara elsevierViewall">En los &#250;ltimos a&#241;os&#44; el mayor conocimiento de la patogenia de la DA&#44; m&#225;s all&#225; del eje Th2&#44; ha permitido el desarrollo de nuevos f&#225;rmacos&#44; t&#243;picos y sist&#233;micos &#8212;biol&#243;gicos y mol&#233;culas peque&#241;as&#8212;&#44; dirigidos frente a elementos clave de la inflamaci&#243;n&#46; Aunque la psoriasis representa una referencia de medicina traslacional por sus similitudes con la DA&#44; los resultados todav&#237;a est&#225;n lejos de los obtenidos en aquella enfermedad&#46; En la actualidad&#44; todav&#237;a est&#225; en discusi&#243;n si la mejor estrategia pasa por la inhibici&#243;n de elementos concretos del proceso inflamatorio a trav&#233;s de anticuerpos monoclonales &#8212;por ejemplo&#44; dupilumab&#8212; o mol&#233;culas m&#225;s transversales y menos espec&#237;ficas &#8212;por ejemplo&#44; upadicitinib&#8212;&#46; El avance en la investigaci&#243;n de las nuevas terapias y la estratificaci&#243;n en los distintos subtipos o subfenotipos de DA en los pr&#243;ximos a&#241;os parece esencial para llegar a tratamientos efectivos&#44; a largo plazo&#44; con un perfil de seguridad aceptable&#44; especialmente en las formas moderadas a graves&#46;</p></span><span id="sec0125" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0150">Conflicto de intereses</span><p id="par0235" class="elsevierStylePara elsevierViewall">J&#46;M&#46; Carrascosa ha recibido honorarios como ponente y asesor para Sanofi y como IP&#47;SI en ensayos cl&#237;nicos para Sanofi&#44; Lilly&#44; Leo-Pharma&#44; Pfizer&#44; Amgen&#46; M&#46; Munera-Campos ha participado y recibido honorarios como SI en ensayos cl&#237;nicos para Lilly&#44; Leo-Pharma y Pfizer&#46;</p></span></span>"
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                  "titulo" => "Bloqueo del receptor de la neuroquinina 1"
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              ]
            ]
            2 => array:3 [
              "identificador" => "sec0085"
              "titulo" => "Tratamientos t&#243;picos"
              "secciones" => array:6 [
                0 => array:2 [
                  "identificador" => "sec0090"
                  "titulo" => "Inhibidores t&#243;picos de la se&#241;alizaci&#243;n JAK&#47;STAT"
                ]
                1 => array:2 [
                  "identificador" => "sec0095"
                  "titulo" => "Inhibidores t&#243;picos de la PDE4"
                ]
                2 => array:2 [
                  "identificador" => "sec0100"
                  "titulo" => "Ominagan"
                ]
                3 => array:2 [
                  "identificador" => "sec0105"
                  "titulo" => "Tapinarof"
                ]
                4 => array:2 [
                  "identificador" => "sec0110"
                  "titulo" => "PR022 &#40;&#225;cido hipocloroso&#41;"
                ]
                5 => array:2 [
                  "identificador" => "sec0115"
                  "titulo" => "SP14019&#47;Cyclatop"
                ]
              ]
            ]
          ]
        ]
        8 => array:2 [
          "identificador" => "sec0120"
          "titulo" => "Conclusiones"
        ]
        9 => array:2 [
          "identificador" => "sec0125"
          "titulo" => "Conflicto de intereses"
        ]
        10 => array:1 [
          "titulo" => "Bibliograf&#237;a"
        ]
      ]
    ]
    "pdfFichero" => "main.pdf"
    "tienePdf" => true
    "fechaRecibido" => "2019-07-05"
    "fechaAceptado" => "2019-11-04"
    "PalabrasClave" => array:2 [
      "es" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Palabras clave"
          "identificador" => "xpalclavsec1273324"
          "palabras" => array:6 [
            0 => "Dermatitis at&#243;pica"
            1 => "Patogenia"
            2 => "Biol&#243;gicos"
            3 => "Dupilumab"
            4 => "JAK"
            5 => "Tratamiento t&#243;pico"
          ]
        ]
      ]
      "en" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Keywords"
          "identificador" => "xpalclavsec1273323"
          "palabras" => array:6 [
            0 => "Atopic dermatitis"
            1 => "Pathogenesis"
            2 => "Biologics"
            3 => "Dupilumab"
            4 => "JAK"
            5 => "Topical treatment"
          ]
        ]
      ]
    ]
    "tieneResumen" => true
    "resumen" => array:2 [
      "es" => array:2 [
        "titulo" => "Resumen"
        "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">La dermatitis at&#243;pica es la dermatosis inflamatoria m&#225;s frecuente y hasta un 20&#37; de los casos pueden clasificarse como moderados a graves&#46; En los &#250;ltimos a&#241;os se ha producido un avance en el conocimiento de la patogenia&#44; centrada en la v&#237;a Th2&#44; pero con una participaci&#243;n marcada de la v&#237;a Th22 y de los ejes Th1 y Th17&#44; de la disfunci&#243;n de la barrera epid&#233;rmica&#44; el prurito y la se&#241;alizaci&#243;n JAK&#47;STAT&#46; Este progreso ha condicionado el desarrollo de nuevas terapias sist&#233;micas&#44; entre las que destacan f&#225;rmacos biol&#243;gicos dirigidos frente a la IL-4&#47;13&#44; como dupilumab&#44; tralokinumab y lebrikizumab&#44; pero tambi&#233;n mol&#233;culas peque&#241;as&#44; como los inhibidores de JAK&#44; entre los que se incluyen baricitinib&#44; upadicitinib y abrocitinib&#46; Entre las innovaciones en los tratamientos t&#243;picos se incluyen los inhibidores de la PDE4 y de JAK&#47;STAT&#46; Este art&#237;culo repasa los principales avances terap&#233;uticos en dermatitis at&#243;pica&#44; para los que son esenciales la caracterizaci&#243;n de los subtipos cl&#237;nicos y moleculares clave en su patog&#233;nesis&#46;</p></span>"
      ]
      "en" => array:2 [
        "titulo" => "Abstract"
        "resumen" => "<span id="abst0015" class="elsevierStyleSection elsevierViewall"><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Atopic dermatitis is the most common inflammatory skin disease and up to 20&#37; of cases can be classified as moderate to severe&#46; Our understanding of the pathogenesis of this disease has improved in recent years&#46; The process is primarily driven by the Th2 pathway&#44; but with significant contributions from the Th22 pathway&#44; the Th1 and Th17 axes&#44; epidermal barrier dysfunction&#44; pruritus&#44; and JAK&#47;STAT signaling&#46; Advances in our understanding of the pathogenesis of atopic dermatitis have led to the development of new systemic treatments&#46; Of particular note are biologic agents targeting IL-4 and IL-13 &#40;e&#46; g&#46;&#44; dupilumab&#44; tralokinumab&#44; and lebrikizumab&#41; and small molecules&#44; such as JAK inhibitors &#40;e&#46; g&#46;&#44; baricitinib&#44; upadacitinib&#44; and abrocitinib&#41;&#46; Novel topical treatments include phosphodiesterase 4 and JAK&#47;STAT inhibitors&#46; In this article&#44; we review the main advances in the treatment of atopic dermatitis&#46; Characterization of clinical and molecular phenotypes with a key pathogenic role is essential for driving these advances&#46;</p></span>"
      ]
    ]
    "multimedia" => array:5 [
      0 => array:7 [
        "identificador" => "fig0005"
        "etiqueta" => "Figura 1"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr1.jpeg"
            "Alto" => 1641
            "Ancho" => 2925
            "Tamanyo" => 411375
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        "descripcion" => array:1 [
          "es" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">F&#225;rmacos biol&#243;gicos y dianas espec&#237;ficas en la patogenia de la dermatitis at&#243;pica&#46;</p> <p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">IgE&#58; inmunoglobulina E&#59; IL&#58; interleucina&#59; OSMR&#946;&#58; receptor &#946; oncostatina M&#59; Th&#58; &#40;linfocito&#41; T helper&#59; TSLP&#58; thymic stromal lymphopoietin&#46;</p>"
        ]
      ]
      1 => array:7 [
        "identificador" => "fig0010"
        "etiqueta" => "Figura 2"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr2.jpeg"
            "Alto" => 1654
            "Ancho" => 2925
            "Tamanyo" => 405816
          ]
        ]
        "descripcion" => array:1 [
          "es" => "<p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">F&#225;rmacos mol&#233;culas peque&#241;as y dianas espec&#237;ficas en la patogenia de la dermatitis at&#243;pica&#46;</p> <p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">AC&#58; <span class="elsevierStyleItalic">adenylyl cyclase&#59;</span> AMPc&#58; adenos&#237;n-monofosfato c&#237;clico&#59; ATP&#58; adenos&#237;n trifosfato&#59; CREB&#58; <span class="elsevierStyleItalic">cAMP response element-binging protein&#59;</span> DGLA&#58; &#225;cido dihomo-&#947;-linol&#233;nico&#59; H4R&#58; receptor de la histamina 4&#59; IL&#58; interleucina&#59; JAK&#58; <span class="elsevierStyleItalic">Janus kinase&#59;</span> &#954;OR&#58; receptor &#954;-opioide&#59; NF-&#954;B&#58; n<span class="elsevierStyleItalic">uclear factor kappa-light-chain-enhancer of activated B cells&#59;</span> NFAT&#58; <span class="elsevierStyleItalic">nuclear factor of activated T-cells&#59;</span> NK-1R&#58; receptor de la neuroquinina 1&#59; PDE4&#58; fosfodiesterasa 4&#59; PGD1&#58; prostaglandina D1&#59; PGD2&#58; prostaglandina D2&#59; PGE1&#58; prostaglandina E1&#59; PKA&#58; <span class="elsevierStyleItalic">protein kinase A&#59;</span> STAT&#58; <span class="elsevierStyleItalic">signal transducer and activator of transcription&#59;</span> Th&#58; &#40;linfocito&#41; T <span class="elsevierStyleItalic">helper&#59;</span> TSLP&#58; <span class="elsevierStyleItalic">thymic stromal lymphopoietin&#59;</span> TYK&#58; <span class="elsevierStyleItalic">tyrosine-kinase&#46;</span></p>"
        ]
      ]
      2 => array:8 [
        "identificador" => "tbl0005"
        "etiqueta" => "Tabla 1"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at1"
            "detalle" => "Tabla "
            "rol" => "short"
          ]
        ]
        "tabla" => array:3 [
          "leyenda" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">BSA&#58; Body Surface Area&#59; CsA&#58; ciclosporina A&#59; DA&#58; dermatitis at&#243;pica&#59; DGLA&#58; &#225;cido dihomo-&#947;-linoleico&#59; DLQI&#58; <span class="elsevierStyleItalic">Dermatology Life Quality Index&#59; GISS&#58; Global Individual Signs Score&#59;</span> DU&#58; dosis &#250;nica&#59; EASI&#58; <span class="elsevierStyleItalic">Eczema Area and Severity Index&#59;</span> H4R&#58; receptor de la histamina 4&#59; IGA&#58; <span class="elsevierStyleItalic">Investigator Global Assessment&#59;</span> IL&#58; interleucina&#59; IV&#58; intravenoso&#59; JAK&#58; <span class="elsevierStyleItalic">Janus kinase&#59;</span> kOR&#58; receptor opioide kappa&#59; NKR1&#58; receptor de la neuroquinina 1&#59; PDE4&#58; fosfodiesterasa 4&#59; SC&#58; subcut&#225;neo&#59; SCORAD&#58; <span class="elsevierStyleItalic">SCORing Atopic Dermatitis&#59;</span> TH&#58; &#40;linfocito&#41; T <span class="elsevierStyleItalic">helper&#59;</span> TSLP&#58; <span class="elsevierStyleItalic">thymic stromal lymphopoietin&#59;</span> TYK&#58; <span class="elsevierStyleItalic">tyrosine-kinase&#59;</span> VO&#58; v&#237;a oral&#46;</p><p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Los datos mencionados espec&#237;ficamente en la tabla pertenecen a los ensayos cl&#237;nicos &#40;ID&#41; se&#241;alados mediante subrayado&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">F&#225;rmaco&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Diana&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">V&#237;a administraci&#243;n&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Gravedad&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Fase&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Estado&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Intervenci&#243;n&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Eficacia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Seguridad&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Ensayos cl&#237;nicos &#40;ID&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="10" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">F&#225;rmacos biol&#243;gicos</span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="10" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Antagonismo del eje TH2</span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="10" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Antagonismo espec&#237;fico de IL-4&#47;IL-13</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Dupilumab&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">IL-4&#44; IL-13 &#40;IL-4R&#945;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">SC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Moderada a grave&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">III<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Completado&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Aleatorizaci&#243;n 1&#58;1&#58;1 &#40;dupilumab 300<span class="elsevierStyleHsp" style=""></span>mg&#47;7<span class="elsevierStyleHsp" style=""></span>d vs&#46; 300<span class="elsevierStyleHsp" style=""></span>mg&#47;15<span class="elsevierStyleHsp" style=""></span>d vs&#46; placebo&#41;Durante 16 semanas&#42;Grupos con dupilumab&#58; dosis de carga de 600<span class="elsevierStyleHsp" style=""></span>mg el d&#237;a 1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Dupilumab 300<span class="elsevierStyleHsp" style=""></span>mg&#47;7<span class="elsevierStyleHsp" style=""></span>d vs&#46; 300<span class="elsevierStyleHsp" style=""></span>mg&#47;15<span class="elsevierStyleHsp" style=""></span>d vs&#46; placeboObjetivo primario&#58; IGA 0-1SOLO-1&#58; 37 vs&#46; 38 vs&#46; 10&#37;SOLO-2&#58; 36 vs&#46; 36 vs&#46; 8&#37;Mejor&#237;a significativa del EASI-75&#44; BSA&#44; SCORAD&#44; GISS&#44; prurito y calidad de vida&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Reacciones en el lugar de inyecci&#243;nConjuntivitis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleUnderline">NCT02277743</span>&#40;SOLO-1&#41;<span class="elsevierStyleUnderline">NCT02277769</span>&#40;SOLO-2&#41;NCT02612454NCT03054428&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Tralokinumab&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">IL-13 &#40;IL-13R&#945;1 e IL-13R&#945;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">SC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Moderada a grave&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">IIbIII&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Completado&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Aleatorizaci&#243;n 1&#58;1&#58;1&#58;1 &#40;tralokinumab 45&#44; 150 y 300<span class="elsevierStyleHsp" style=""></span>mg&#47;15<span class="elsevierStyleHsp" style=""></span>d vs&#46; placebo&#41;Uso concomitante de corticoides t&#243;picos&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Tralokinumab 300<span class="elsevierStyleHsp" style=""></span>mg&#58; reducci&#243;n del EASI &#40;diferencia media ajustada&#44; &#8722;4&#44;94&#59; IC 95&#37; &#8722;8&#44;76 a &#8722;1&#44;13&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;01&#41;&#46; IGA 0-1&#58; 26&#44;7 vs&#46; 11&#44;8&#37; para placebo&#46; Mejor&#237;a significativa del SCORAD&#44; DLQI y prurito&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Reacciones en el lugar de inyecci&#243;n&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleUnderline">NCT02347176</span>NCT03131648NCT03160885NCT03363854NCT03526861&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Lebrikizumab&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">IL-13&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">SC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Moderada a grave&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">II&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Completado&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Aleatorizaci&#243;n 1&#58;1&#58;1&#58;1 &#40;lebrikizumab 125<span class="elsevierStyleHsp" style=""></span>mg &#40;DU&#41; vs&#46; 250<span class="elsevierStyleHsp" style=""></span>mg &#40;DU&#41; vs&#46; 125<span class="elsevierStyleHsp" style=""></span>mg&#47;4<span class="elsevierStyleHsp" style=""></span>s vs&#46; placebo&#41;Uso concomitante de corticoides t&#243;picos&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Objetivo primarioEASI-50&#58; lebrikizumab 125<span class="elsevierStyleHsp" style=""></span>mg&#47;4<span class="elsevierStyleHsp" style=""></span>s &#40;82&#44;4&#37;&#41; vs&#46; placebo &#40;62&#44;3&#37;&#41;&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;026&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Reacciones en el lugar de inyecci&#243;nInfecciones herp&#233;ticas leves&#44; eosinofilia perif&#233;rica&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleUnderline">NCT02340234</span>NCT03443024&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="10" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="10" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Antagonismo de la polarizaci&#243;n Th2&#58; TSLP&#44; OX40L e IL-33</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Tezepelumab&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">TSLP&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">SC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Moderada a grave&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">IIaIIb&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Completado&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Aleatorizaci&#243;n 1&#58;1 &#40;tezepelumab 280<span class="elsevierStyleHsp" style=""></span>mg&#47;2<span class="elsevierStyleHsp" style=""></span>s vs&#46; placebo&#41;Uso concomitante de corticoides t&#243;picos&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">EASI-50 &#40;tezepelumab 64&#44;7&#37; vs&#46; placebo 48&#44;2&#37;&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;091&#41;No diferencias estad&#237;sticamente significativas&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Reacciones en el lugar de inyecci&#243;n&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleUnderline">NCT02525094</span>NCT03809663&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>MK-8226&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">TSLP-R&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">IV&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Moderada a grave&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">I&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Suspendido&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleUnderline">NCT01732510</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">GBR 830&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">OX40&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">IVSC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Moderada a grave&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">IIaIIb&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Completado&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Aleatorizaci&#243;n 3&#58;1GBR 830 10<span class="elsevierStyleHsp" style=""></span>mg&#47;kg vs&#46; placebo d&#237;as 1 y 29&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Porcentaje de pacientes que alcanzan EASI-50 con GBR 830 superior a placebo&#44; pero no diferencias estad&#237;sticamente significativas &#40;44 vs&#46; 20&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Buena tolerancia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleUnderline">NCT02683928</span>NCT03568162&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>KHK4083&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">OX40&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">IV&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Moderada a grave&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">III&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Completado&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">KHK-4083 0&#44;003 y 0&#44;001<span class="elsevierStyleHsp" style=""></span>mg&#47;kg y dosis ascendentes hasta 10<span class="elsevierStyleHsp" style=""></span>mg&#47;kg&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Tolerancia&#44; seguridad&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Buena tolerancia&#46; Se ha descrito el desarrollo de anticuerpos anti-KHK4083&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleUnderline">NCT03096223</span>NCT03703102&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Etokinab &#40;ANB020&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">IL-33&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">SC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Moderada a grave&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">II&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Activo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Etokinab vs&#46; placebo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleUnderline">NCT03533751</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="10" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="10" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Antagonismo de la respuesta TH22</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Fezakinumab&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">IL-22&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">IV&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Moderada a grave&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">II&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Completado&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Aleatorizaci&#243;n 2&#58;1Fezakinumab 600<span class="elsevierStyleHsp" style=""></span>mg &#40;d&#237;a 0&#41;&#44; seguido de 300<span class="elsevierStyleHsp" style=""></span>mg&#47;2<span class="elsevierStyleHsp" style=""></span>s &#40;&#250;ltima administraci&#243;n la semana 10&#41; vs&#46; placebo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Reducci&#243;n del SCORAD solo en el subgrupo de DA grave a las 12 semanas &#40;36&#44;4 vs&#46; 22&#44;3&#37;&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;05&#41; y a las 20 semanas &#40;46&#44;2 vs&#46; 22&#44;6&#37;&#59; p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;01&#41;&#46; No significaci&#243;n estad&#237;stica en el total &#40;incluyendo DA moderada&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Nasofaringitis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleUnderline">NCT01941537</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="10" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="10" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Antagonismo de la respuesta TH17 e IL-23</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Secukinumab&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">IL-17A&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">SC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Moderada a grave&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">II&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Completado&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Estudio paralelo con secukinumab &#40;misma posolog&#237;a que en psoriasis&#41; vs&#46; placebo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Evaluaci&#243;n a las 16 semanas&#46; Pendiente de publicaci&#243;n de resultados&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Buena tolerancia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleUnderline">NCT02594098</span>NCT03568136&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">MOR106&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">IL-17C&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">IV&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Moderada a grave&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">II&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Activo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">MOR106 a distintas dosis vs&#46; placebo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleUnderline">NCT03568071</span>NCT03689829NCT03864627&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Ustekinumab&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">IL-12&#44; IL-23 &#40;p40&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">SC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Moderada a grave&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">II&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Completado&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Estudio cruzado con ustekinumab &#40;misma posolog&#237;a que en psoriasis&#41; vs&#46; placebo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Mayor porcentaje de pacientes lograron una respuesta SCORAD-50 vs&#46; placebo&#44; pero no estad&#237;sticamente significativa&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Buena tolerancia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleUnderline">NCT01806662</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="10" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="10" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Bloqueo de la v&#237;a IL-31 y OSMR&#946;</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Nemolizumab&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">IL-31RA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">SC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Moderada a grave&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">II&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Completado&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Aleatorizaci&#243;n 1&#58;1&#58;1&#58;1Nemolizumab &#40;0&#44;1&#44; 0&#44;5 o 2<span class="elsevierStyleHsp" style=""></span>mg&#47;kg&#44; placebo&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Reducciones significativas del prurito dependientes de dosis para nemolizumab &#40;&#8722;63&#44;1&#37; para dosis de 0&#44;5<span class="elsevierStyleHsp" style=""></span>mg&#47;kg vs&#46; &#8722;20&#44;9&#37;&#41;&#46; Mejor&#237;a del EASI y SCORAD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Reacciones en el lugar de inyecci&#243;n&#44; nasofaringitis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleUnderline">NCT01986933</span>NCT03100344&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>BMS-981164&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">IL-31&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">SC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Moderada a grave&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">I&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Suspendido&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Sin resultados&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleUnderline">NCT01614756</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">KPL-716&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">OSMR&#946;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">IV&#47;SC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Moderada a grave&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Ia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Completado&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Dosis de 0&#44;3&#44; 1&#44;5 y 7&#44;5<span class="elsevierStyleHsp" style=""></span>mg&#47;kg vs&#46; placebo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Mejores resultados en reducci&#243;n del EASI y del prurito para las dosis de 7&#44;5<span class="elsevierStyleHsp" style=""></span>mg&#47;kg vs&#46; placebo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Buena toleranciaCefalea&#44; hiporexia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Mikhak et al&#46;<a class="elsevierStyleCrossRef" href="#bib0530"><span class="elsevierStyleSup">44</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="10" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="10" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Antagonismo de la IgE o de IL-5</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Omalizumab &#40;aprobado en asma&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">IgE&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">IV&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Moderada a graveGrave&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">IIIV&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CompletadoActivo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">OmalizumabOmalizumab vs&#46; placebo en pacientes de 4-19 a&#241;os con IgE<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>300<span class="elsevierStyleHsp" style=""></span>KU&#47;l&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Resultados no publicados-&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Resultados no publicados-&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleUnderline">NCT01179529</span><span class="elsevierStyleUnderline">NCT02300701</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Ligelizumab &#40;QGE031&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">IgE &#40;mayor afinidad que omalizumab&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">SC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Moderada a grave&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">II&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Completado&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Aleatorizaci&#243;n 1&#58;1&#58;1 &#40;ligelizumab&#47;2<span class="elsevierStyleHsp" style=""></span>s vs&#46; placebo vs&#46; CsA&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Resultados no publicados&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Resultados no publicados&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleUnderline">NCT01552629</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Mepolizumab &#40;aprobado en asma&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">IL-5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">SC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Moderada a grave&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">II&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Suspendido &#40;futilidad&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Mepolizumab 100<span class="elsevierStyleHsp" style=""></span>mg&#47;4<span class="elsevierStyleHsp" style=""></span>s vs&#46; placebo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Finalizaci&#243;n prematura del ensayo tras an&#225;lisis estad&#237;stico intermedio&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">No se ha demostrado eficacia&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleUnderline">NCT03055195</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="10" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="10" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">F&#225;rmacos mol&#233;cula peque&#241;a</span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="10" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Inhibici&#243;n de la v&#237;a de se&#241;alizaci&#243;n JAK-STAT</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Baricitinib&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">JAK1&#44; JAK2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">VO&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Moderada a grave&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">IIIII&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CompletadoActivo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Aleatorizaci&#243;n 1&#58;1&#58;1 &#40;baricitinib 2<span class="elsevierStyleHsp" style=""></span>mg&#44; 4<span class="elsevierStyleHsp" style=""></span>mg&#44; placebo&#41; 1<span class="elsevierStyleHsp" style=""></span>v&#47;dJunto a aplicaci&#243;n t&#243;pica de corticoides&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">EASI-50&#58; mayor proporci&#243;n de pacientes para baricitinib 4<span class="elsevierStyleHsp" style=""></span>mg&#47;d vs&#46; placebo &#40;61 vs&#46; 37&#37;&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;027&#41; a las 16 semanas&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Buena tolerancia &#40;no casos de neoplasia&#44;eventos tromb&#243;ticos ni cardiovasculares&#41;&#44; ni herpes z&#243;ster&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleUnderline">NCT02576938</span>NCT03334396NCT03334422NCT03334435NCT03428100NCT03435081NCT03559270NCT03733301NCT03952559&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Upadacitinib &#40;ABT-494&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">JAK1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">VO&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Moderada a grave&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">IIbIII&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CompletadoActivo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Aleatorizaci&#243;n 1&#58;1&#58;1&#58;1 &#40;upadacitinib 7&#44;5&#44; 15 y 30<span class="elsevierStyleHsp" style=""></span>mg vs&#46; placebo&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Reducci&#243;n media del EASI a las 16 semanas a dosis de 30&#47;15&#47;7&#44;5<span class="elsevierStyleHsp" style=""></span>mg fue del 74&#47;62&#47;39&#37; vs&#46; placebo &#40;23&#37;&#41;&#59; p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;05&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Buena tolerancia&#46; Infecciones respiratorias de v&#237;as altas y acn&#233;&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleUnderline">NCT02925117</span>NCT03607422NCT03568318NCT03738397NCT03661138&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Abrocitinib &#40;PF-04965842&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">JAK1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">VO&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Moderada a grave&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">IIbIII&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CompletadoActivo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Aleatorizaci&#243;n 1&#58;1&#58;1&#58;1&#58;1 &#40;abrocitinib 10&#44; 30&#44; 100 y 200<span class="elsevierStyleHsp" style=""></span>mg&#44; placebo&#41; 1<span class="elsevierStyleHsp" style=""></span>v&#47;d&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Porcentaje IGA 0-1 y mejor&#237;a de<span class="elsevierStyleHsp" style=""></span>&#8805;<span class="elsevierStyleHsp" style=""></span>2 puntos respecto el basal&#44; significativamente mayor para abrocitinib 200<span class="elsevierStyleHsp" style=""></span>mg&#47;d vs&#46; placebo &#40;44&#44;5 vs&#46; 6&#44;3&#37;&#41; a las 12 semanas&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Buena tolerancia&#44; un caso de eccema herpeticum y uno de neumon&#237;a&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleUnderline">NCT02780167</span>NCT03349060NCT03422822NCT03575871NCT03627767NCT03720470&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ASN002&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">PAN-JAK &#40;JAK1&#44; JAK2&#44; JAK3&#44; TYK&#41;&#44; SYK&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">VO&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Moderada a grave&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">III&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Completado&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Aleatorizaci&#243;n 1&#58;1&#58;1&#58;1 &#40;ASN002 20&#44; 40 y 80<span class="elsevierStyleHsp" style=""></span>mg vs&#46; placebo&#41;Durante 28 d&#237;as&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Proporci&#243;n de pacientes que alcanzan EASI-75 significativamente superior para ASN002 40<span class="elsevierStyleHsp" style=""></span>mg &#40;71&#44;4&#37;&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;06&#41; y para ASN002 80<span class="elsevierStyleHsp" style=""></span>mg &#40;33&#44;3&#37;&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;65&#41; vs&#46; placebo &#40;22&#44;2&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Buena tolerancia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleUnderline">NCT03139981</span>NCT03531957&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="10" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="10" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Antagonismo de la PDE4</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Apremilast&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">PDE4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">VO&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Moderada a grave&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">II&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Completado&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Dise&#241;o paralelo 1&#58;1&#58;1&#58;1 &#40;apremilast 30<span class="elsevierStyleHsp" style=""></span>mg&#47;12<span class="elsevierStyleHsp" style=""></span>h&#44; 40<span class="elsevierStyleHsp" style=""></span>mg&#47;12<span class="elsevierStyleHsp" style=""></span>h vs&#46; placebo&#47;apremilast 30<span class="elsevierStyleHsp" style=""></span>mg&#47;12<span class="elsevierStyleHsp" style=""></span>h vs&#46; placebo&#47;apremilast 40<span class="elsevierStyleHsp" style=""></span>mg&#47;12<span class="elsevierStyleHsp" style=""></span>h&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Reducci&#243;n significativa del EASI respecto al basal a las 12 semanas de apremilast 40<span class="elsevierStyleHsp" style=""></span>mg&#47;12<span class="elsevierStyleHsp" style=""></span>h vs&#46; placebo &#40;31&#44;57 vs&#46; 10&#44;98&#37;&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;034&#41;&#46; No ventajas respecto a EASI-50 ni prurito&#46; No diferencias significativas a 30<span class="elsevierStyleHsp" style=""></span>mg&#47;12<span class="elsevierStyleHsp" style=""></span>h&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Diarrea&#44; n&#225;useas&#44; molestias abdominales&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleUnderline">NCT02087943</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="10" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="10" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Antagonismo del H4R</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">JNJ-39758979&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">H4R&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">VO&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Moderada&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">II&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Suspendido &#40;efectos adversos&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">JNJ-39758979 300 o 100<span class="elsevierStyleHsp" style=""></span>mg vs&#46; placebo 1<span class="elsevierStyleHsp" style=""></span>v&#47;d&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Terminaci&#243;n temprana del ensayo cl&#237;nico&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Dos casos de neutropenia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleUnderline">NCT01497119</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ZPL389&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">H4R&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">VO&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Moderada a grave&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">II&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Completado&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ZPL-389 30<span class="elsevierStyleHsp" style=""></span>mg vs&#46; placebo 1<span class="elsevierStyleHsp" style=""></span>v&#47;d&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Mejor&#237;a significativa del EASI &#40;50 vs&#46; 27&#37;&#41;&#46; No diferencias significativas en cuanto al prurito&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Buena tolerancia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleUnderline">NCT02424253</span>NCT03517566&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="10" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="10" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Bloqueo del NKR1</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Serlopitant&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NKR1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">VO&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Leve&#44; moderada o grave&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">II&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Completado&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Aleatorizaci&#243;n 1&#58;1&#58;1 &#40;serlopitant 1 y 5<span class="elsevierStyleHsp" style=""></span>mg vs&#46; placebo&#41;6 semanas&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Reducci&#243;n del prurito no significativa frente a placebo &#40;&#8722;2&#44;25 vs&#46; &#8722;2&#44;32 vs&#46; &#8722;2&#44;01&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Buena tolerancia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleUnderline">NCT02975206</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Tradipitant&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NKR1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">VO&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Leve&#44; moderada o grave&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">IIIIIII&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CompletadoCompletadoActivo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Aleatorizaci&#243;n 1&#58;1 &#40;tradipitant 100<span class="elsevierStyleHsp" style=""></span>mg&#47;24<span class="elsevierStyleHsp" style=""></span>h vs&#46; placebo&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Reducci&#243;n del prurito no significativa frente a placeboSin otros resultados&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Buena tolerancia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleUnderline">NCT02004041</span>NCT02651714NCT03568331&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="10" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="10" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Agonismo del kOR</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Asimadolina&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Agonista del kOR&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">VO&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Leve&#44; moderada o grave&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">II&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Completado&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Aleatorizaci&#243;n 1&#58;1 &#40;amisadolina 2&#44;5<span class="elsevierStyleHsp" style=""></span>mg&#47;12<span class="elsevierStyleHsp" style=""></span>h vs&#46; placebo&#47;12<span class="elsevierStyleHsp" style=""></span>h&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Sin resultados&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Sin resultados&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NCT02475447&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="10" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="10" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Otras mol&#233;culas</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">DS107&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">DGLA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">VO&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Moderada a grave&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">II&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Completado&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Aleatorizaci&#243;n 1&#58;1&#58;1 &#40;DS107 1<span class="elsevierStyleHsp" style=""></span>g vs&#46; 2<span class="elsevierStyleHsp" style=""></span>g vs&#46; placebo&#41;1<span class="elsevierStyleHsp" style=""></span>v&#47;d&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Resultados no publicados&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Resultados no publicados&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NCT02864498&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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          "es" => "<p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Resumen de los tratamientos sist&#233;micos de nuevo desarrollo y en fases de investigaci&#243;n para dermatitis at&#243;pica</p>"
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          "leyenda" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">ADSI&#58; <span class="elsevierStyleItalic">Atopic Dermatitis Severity Index&#59;</span> AhR&#58; <span class="elsevierStyleItalic">aryl hydrocarbon receptor&#59;</span> BSA&#58; Body Surface Area&#59; CRTH2&#58; receptor transmembrana de la prostaglandina 2&#59; CsA&#58; ciclosporina A&#59; EASI&#58; <span class="elsevierStyleItalic">Eczema Area and Severity Index&#59;</span> EVA&#58; escala visual anal&#243;gica&#59; IGA&#58; <span class="elsevierStyleItalic">Investigator Global Assessment&#59;</span> LXR&#58; <span class="elsevierStyleItalic">liver X receptors&#59;</span> JAK&#58; Janus kinase&#59; PAM&#58; p&#233;ptido antimicrobiano&#59; PDE4&#58; fosfodiesterasa 4&#59; PGA&#58; physician global assessment&#59; SCORAD&#58; <span class="elsevierStyleItalic">SCORing Atopic Dermatitis&#59;</span> SYK&#58; <span class="elsevierStyleItalic">spleen tyrosine kinase&#59;</span> TEWL&#58; <span class="elsevierStyleItalic">transepidermal water loss&#59;</span> TrkA&#58; <span class="elsevierStyleItalic">tyrosine receptor kinase-A&#46;</span></p><p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">Los datos mencionados espec&#237;ficamente en la tabla pertenecen a los ensayos cl&#237;nicos &#40;ID&#41; se&#241;alados mediante subrayado&#46;</p>"
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                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">F&#225;rmaco&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Diana&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Gravedad&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Fase&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Estado&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Intervenci&#243;n&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Eficacia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Seguridad&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Ensayos cl&#237;nicos &#40;ID&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="9" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Inhibidores t&#243;picos de la se&#241;alizaci&#243;n JAK&#47;STAT</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Tofacitinib&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">PAN-JAK &#40;m&#225;s selectivo JAK1 y JAK3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Leve a moderada&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">II&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Completado&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Aleatorizaci&#243;n 1&#58;1Tofacitinib 2&#37; t&#243;pico vs&#46; placebo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Mejor&#237;a del EASI respecto al basal significativamente superior al veh&#237;culo &#40;&#8722;81&#44;7 vs&#46; &#8722;29&#44;9&#37;&#59; p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#41;&#46; Mejor&#237;as significativas del PGA&#44; BSA y del prurito&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Buena tolerancia&#46; Dolor&#47;quemaz&#243;n en el lugar de aplicaci&#243;n&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleUnderline">NCT02001181</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Ruxolitinib&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">JAK1&#44; JAK2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Leve a moderada&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">II&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Completado&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Ruxolitinib a distintas concentraciones vs&#46; triamcinolona 0&#44;1&#37; vs&#46; placebo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Mejor&#237;a del EASI respecto al basal significativamente superior al placebo para las dosis de 1&#44;5&#37; &#63;una o 2 veces al d&#237;a&#63; y 0&#44;5&#37; &#63;una vez al d&#237;a&#63; a las 4 semanas &#40;71&#44;6&#47;67&#47;52&#44;2&#37; vs&#46; 15&#44;5&#37;&#59; p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Buena tolerancia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleUnderline">NCT03011892</span>NCT03257644NCT03745651NCT03920852&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Cerdulatinib &#40;RVT-502&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">PAN-JAK&#44; SYK&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">I&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Delgocitinib &#40;JTE-052&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">PAN-JAK&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Moderada a grave&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">II&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Completado&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Aleatorizaci&#243;n 2&#58;2&#58;2&#58;2&#58;1&#58;1 &#40;delgocitinib 0&#44;25&#37;&#44; 0&#44;5&#37;&#44; 1&#37;&#44; 3&#37;&#44; veh&#237;culo&#44; tacrolimus 0&#44;1&#37;&#41; 2<span class="elsevierStyleHsp" style=""></span>v&#47;d&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Mejor&#237;a del EASI respecto al basal para todas las dosis de delgocitinib &#40;0&#44;25&#44; 0&#44;5&#44; 1 y 3&#37;&#41; significativamente superior al veh&#237;culo &#40;&#8722;41&#44;7&#44; &#8722;57&#44;1&#44; &#8722;54&#44;9&#44; &#8722;72&#44;9 vs&#46; 12&#44;2&#37;&#44; respectivamente&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#41;&#46; Reducci&#243;n del prurito&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Buena tolerancia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleUnderline">JapicCTI-152887</span>NCT03725722NCT03826901NCT03683719&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>SNA-125&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">JAK3&#44; TrkA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">I&#47;II&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="9" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="9" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Inhibidores de la PDE4</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Crisaborol&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">PDE4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Leve a moderada&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">III&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Completado&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2 ensayos de intervenci&#243;n id&#233;ntica&#44; pacientes<span class="elsevierStyleHsp" style=""></span>&#8805;<span class="elsevierStyleHsp" style=""></span>2 a&#241;osAleatorizaci&#243;n 2&#58;1 &#40;crisaborol&#58;veh&#237;culo&#41;Aplicaci&#243;n 2 veces al d&#237;a&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Evaluaci&#243;n a las 4 semanas del IGA 0&#47;1&#44; con mejor&#237;as significativas frente al veh&#237;culo&#58; 51&#44;7 vs&#46; 40&#44;6&#37;&#44; p&#160;&#61;&#160;0&#44;005&#59; 48&#44;5 vs&#46; 29&#44;7&#37;&#44; p&#160;&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;0019&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Dolor&#47;quemaz&#243;n en el lugar de aplicaci&#243;n&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleUnderline">NCT02118766</span><span class="elsevierStyleUnderline">NCT02118792</span>NCT01301508NCT01602341NCT01652885NCT03233529NCT03260595NCT03250663&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>E6005&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">PDE4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Leve a moderada&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">II&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Completado&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Aleatorizaci&#243;n 1&#58;1 &#40;E6005 0&#44;2&#37; vs&#46; veh&#237;culo&#41;Aplicaci&#243;n 2 veces al d&#237;a&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Evaluaci&#243;n a la semana 12&#58; reducci&#243;n significativa del EASI respecto al basal &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;030&#41; y SCORAD &#40;&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Buena tolerancia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleUnderline">NCT01461941</span>NCT01179880NCT02094235&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>AN2898&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">PDE4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Leve a moderada&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">II&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Completado&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Comparaci&#243;n con placebo de AN2898 al 2&#37; en una lesi&#243;n activa vs&#46; placebo en otra lesi&#243;n activaAplicaci&#243;n 2 veces al d&#237;a&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Mejor&#237;a significativa del ADSI respecto al basal&#44; mayor proporci&#243;n de lesiones con aclaramiento total o parcial ADSI<span class="elsevierStyleHsp" style=""></span>&#8804;<span class="elsevierStyleHsp" style=""></span>2&#59; 48 vs&#46; 33&#37;&#41; en comparaci&#243;n con el veh&#237;culo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Buena tolerancia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleUnderline">NCT01301508</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>MM36 &#40;OPA-15406&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">PDE4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Leve a moderada&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">IIIII&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CompletadoActivo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Aleatorizaci&#243;n 1&#58;1&#58;1MM36 0&#44;3&#37; vs&#46; 1&#37; vs&#46; veh&#237;culoAplicaci&#243;n 2 veces al d&#237;a&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Reducci&#243;n de IGA de 0&#47;1 o reducci&#243;n en 2 puntos&#58; MM36 al 1&#37;&#58; 20&#44;9 vs&#46; 2&#44;7&#37; para el veh&#237;culo&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;0165&#41; a la semana 4&#46; Reducci&#243;n de EASI&#58; OPA-15406 al 1&#37;&#58; 39 vs&#46; 3&#37; para el veh&#237;culo&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;005&#41; a la semana 2Reducci&#243;n del prurito&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Buena tolerancia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleUnderline">NCT02068352</span>NCT02945657NCT02914548NCT03018691NCT01702181NCT02334787NCT03961529&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Roflumilast&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">PDE4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Moderada&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">IIa&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Completado&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Aleatorizaci&#243;n 1&#58;1Roflumilast 0&#44;5&#37; vs&#46; veh&#237;culoAplicaci&#243;n 2 veces al d&#237;a&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">No se observaron diferencias en SCORAD&#44; prurito &#40;EVA 100<span class="elsevierStyleHsp" style=""></span>mm&#41; ni TEWL a la semana 2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Buena tolerancia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleUnderline">NCT01856764</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="9" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="9" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Otras dianas</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Omiganan&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Es un PAM&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Leve a moderada&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">II&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Completado&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Aleatorizaci&#243;n 1&#58;1&#58;1&#58;1 &#40;omiganan 1&#37;&#44; 1&#44;75&#37;&#44; 2&#44;5&#37;&#44; veh&#237;culo&#41;Aplicaci&#243;n 2 veces al d&#237;a&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Evaluaci&#243;n a las 7 semanas del SCORAD&#44; EASI e IGAResultados no publicados&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Resultados no publicados&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NCT03091426NCT02456480&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Tapinarof &#40;GSK2894512&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Agonista del AhR&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Moderada a grave&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">II&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Completado&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Aleatorizaci&#243;n 1&#58;1&#58;1&#58;1&#58;1&#58;1 &#40;tapinarof 1&#37; 2<span class="elsevierStyleHsp" style=""></span>v&#47;d&#44; 1&#37; 1<span class="elsevierStyleHsp" style=""></span>v&#47;d&#44; 0&#44;5&#37; 2<span class="elsevierStyleHsp" style=""></span>v&#47;d&#44; 0&#44;5&#37; 1<span class="elsevierStyleHsp" style=""></span>v&#47;d&#44; veh&#237;culo 2<span class="elsevierStyleHsp" style=""></span>v&#47;d&#44; veh&#237;culo 1<span class="elsevierStyleHsp" style=""></span>v&#47;d&#41;&#42;Pacientes de 12-65 a&#241;os&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Proporci&#243;n de pacientes con IGA de 0 o 1&#58; 53&#37; &#40;tapinarof 1&#37; 2<span class="elsevierStyleHsp" style=""></span>v&#47;d&#41; vs&#46; 24&#37; &#40;veh&#237;culo 2<span class="elsevierStyleHsp" style=""></span>v&#47;d&#41; a las 12 semanas&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Buena toleranciaDermatitis de contacto &#40;infrecuente&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleUnderline">NCT02564055</span>NCT01098734NCT00837551&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>PR022&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#193;cido hipocloroso&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Leve a moderada&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">II&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Activo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Aleatorizaci&#243;n 1&#58;1&#58;1 &#40;PR022 al 0&#44;05&#37;&#44; 0&#44;1&#37;&#44; veh&#237;culo&#41;Durante 28 d&#237;as&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Sin resultados&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Sin resultados&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleUnderline">NCT03351777</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>SP14019&#47;Cyclatop&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CsA t&#243;pica&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Leve a moderada&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">II&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Completado&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Aleatorizaci&#243;n 1&#58;1Soluci&#243;n de ciclosporina al 5&#37; vs&#46; veh&#237;culoDurante 4 semanasPacientes<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>2 a&#241;os&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Mejor&#237;as significativas de Cyclatop frente a veh&#237;culo en EASI &#40;51&#44;2 vs&#46; 23&#44;6&#37;&#41;&#44; ADSI &#40;55&#44;4 vs&#46; 34&#37;&#41; e IGA &#40;61&#44;5&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Buena tolerancia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleUnderline">NCT02865356</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Q301&#47;Zyleuton&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Antagonista del CRTH2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Moderada a grave&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">II&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Completado&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Aleatorizaci&#243;n 1&#58;1Q301 en crema &#40;dosis no conocidas&#41; al vs&#46; placebo&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">Resultados no publicados&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Resultados no publicados&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleUnderline">NCT02426359</span>NCT03571620&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>VTP-38543&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">I&#47;II&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">No reducci&#243;n significativa del EASI ni del SCORAD frente al veh&#237;culo&nbsp;\t\t\t\t\t\t\n
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REVISIÓN
Innovación en dermatitis atópica: de la patogenia a la terapéutica
Innovation in Atopic Dermatitis: From Pathogenesis to Treatment
M. Munera-Campos
Corresponding author
monicamunera@hotmail.com

Autor para correspondencia.
, J.M. Carrascosa
Servicio de Dermatología, Hospital Universitari Germans Trias i Pujol, Universitat Autònoma de Barcelona, Badalona, Barcelona, España
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la funci&#243;n inmunol&#243;gica y el ambiente&#46; En los &#250;ltimos a&#241;os ha ocurrido una aut&#233;ntica revoluci&#243;n en la investigaci&#243;n traslacional que ha permitido profundizar en el conocimiento de la patogenia de la DA y en el desarrollo de nuevas mol&#233;culas dirigidas a elementos clave de la inflamaci&#243;n&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">Este art&#237;culo revisa aquellos aspectos clave en la patogenia de la enfermedad con repercusi&#243;n en potenciales dianas terap&#233;uticas&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Patogenia</span><p id="par0020" class="elsevierStylePara elsevierViewall">La DA se ha considerado un modelo de disbalance entre las respuestas de los linfocitos T <span class="elsevierStyleItalic">helper</span> &#40;Th&#41; 1&#47;Th2&#44; con distorsi&#243;n hacia un predominio Th2&#46; Los linfocitos Th2 producen interleucina &#40;IL&#41;-4 e IL-13&#44; que inhiben la expresi&#243;n de filagrina&#44; circunstancia que permite establecer una relaci&#243;n entre la disfunci&#243;n inmunol&#243;gica y la alteraci&#243;n de la funci&#243;n de barrera caracter&#237;stica de la DA<a class="elsevierStyleCrossRef" href="#bib0330"><span class="elsevierStyleSup">4</span></a>&#46; En los &#250;ltimos a&#241;os&#44; diversos estudios traslacionales han centrado la patogenia de la DA en una respuesta Th2&#47;Th22 durante todo su curso&#44; con cierta participaci&#243;n de Th17&#44; y con una contribuci&#243;n adicional del eje Th1 en su etapa cr&#243;nica<a class="elsevierStyleCrossRef" href="#bib0335"><span class="elsevierStyleSup">5</span></a>&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">Sin embargo&#44; este esquema es una evidente simplificaci&#243;n&#44; y la mayor o menor contribuci&#243;n de estas respuestas variar&#225; entre los subtipos de la enfermedad&#46; En este sentido&#44; se han caracterizado al menos 3 fenotipos inmunol&#243;gicos de DA&#44; en los que destaca la contribuci&#243;n de la respuesta Th17&#44; a pesar de que mantienen una activaci&#243;n importante Th2&#47;Th22&#58; la DA pedi&#225;trica&#44; que muestra una mayor participaci&#243;n de la inmunidad innata&#44; IL-9 e IL-33&#59; la variante intr&#237;nseca &#40;20&#37; de los adultos&#41;&#44; que t&#237;picamente se presenta con niveles normales de IgE y sin antecedentes personales o familiares de atopia&#44; y&#44; por &#250;ltimo&#44; el fenotipo asi&#225;tico&#44; en el que predominan fenotipos con marcada liquenificaci&#243;n o psoriasiformes<a class="elsevierStyleCrossRefs" href="#bib0340"><span class="elsevierStyleSup">6&#8211;8</span></a>&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">Existen adem&#225;s otros potenciales actores relevantes en el proceso patog&#233;nico&#46; De este modo&#44; los queratinocitos son un elemento activo y producen citocinas&#44; como el <span class="elsevierStyleItalic">thymic stromal lymphopoietin</span> &#40;TSLP&#41; 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capaz de perpetuar la respuesta Th2 y la sobreexpresi&#243;n de IL-4&#44; IL-13 e IL-22&#46; Esta mayor colonizaci&#243;n est&#225; facilitada por la menor expresi&#243;n de p&#233;ptidos antimicrobianos en la piel lesional y aparentemente sana de los pacientes con DA&#44; tambi&#233;n relacionada con la v&#237;a IL-4&#47;13 &#40;<a class="elsevierStyleCrossRef" href="#fig0005">fig&#46; 1</a>&#41;<a class="elsevierStyleCrossRef" href="#bib0330"><span class="elsevierStyleSup">4</span></a>&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0040" class="elsevierStylePara elsevierViewall">Frente a la identificaci&#243;n de mol&#233;culas clave en la patogenia y&#44; por tanto&#44; potencialmente dianas terap&#233;uticas de anticuerpos monoclonales espec&#237;ficos&#44; se ha establecido la importancia de otras mol&#233;culas implicadas de forma transversal en el proceso inflamatorio&#46; En este apartado se ha estudiado la participaci&#243;n de la v&#237;a <span class="elsevierStyleItalic">Janus kinase&#47;signal transducer and activator of transcription</span> &#40;JAK-STAT&#41;&#44; activada por la IL-4&#44; en la desregulaci&#243;n inmune en la DA&#46; La familia de las JAK est&#225; formada por 4 miembros &#40;JAK1&#44; JAK2&#44; JAK3 y tirosina cinasa 2 &#91;TYK2&#93;&#41; y&#44; a diferencia de lo que ocurre en la alopecia areata o la psoriasis&#44; los 4 intervienen en la DA<a class="elsevierStyleCrossRef" href="#bib0360"><span class="elsevierStyleSup">10</span></a>&#46; Los distintos elementos de esta familia forman parte de los receptores citopl&#225;smicos de numerosas IL &#40;<a class="elsevierStyleCrossRef" href="#fig0010">fig&#46; 2</a>&#41;&#46; Su inhibici&#243;n tendr&#237;a&#44; por lo tanto&#44; un impacto en numerosas IL implicadas en la respuesta Th2 y la activaci&#243;n de los eosin&#243;filos<a class="elsevierStyleCrossRef" href="#bib0365"><span class="elsevierStyleSup">11</span></a>&#46;</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0045" class="elsevierStylePara elsevierViewall">El mayor conocimiento de las v&#237;as inflamatorias de la DA ha llevado al desarrollo de f&#225;rmacos dirigidos frente a distintas citocinas de forma espec&#237;fica&#44; as&#237; como en las v&#237;as del prurito&#44; y f&#225;rmacos de acci&#243;n amplia&#44; que intervienen sobre la se&#241;alizaci&#243;n intracelular&#44; afectando a la producci&#243;n final de diversas citocinas&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Tratamientos sist&#233;micos</span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">F&#225;rmacos biol&#243;gicos</span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Antagonismo de la respuesta celular Th2 &#40;IL-4 e IL-13&#41;</span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Bloqueo de la v&#237;a IL-4&#47;IL-13</span><p id="par0050" class="elsevierStylePara elsevierViewall">La IL-4 y la IL-13&#44; elementos clave de la respuesta Th2&#44; inician y dirigen la respuesta inmune en la DA&#44; de modo que el antagonismo espec&#237;fico frente a estas citocinas ha supuesto una revoluci&#243;n terap&#233;utica en esta enfermedad&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">Dupilumab es un anticuerpo monoclonal que inhibe la IL-4 y la IL-13 al bloquear la subunidad &#945; compartida en sus receptores &#40;IL-4R&#945;&#41;&#46; En 2 ensayos cl&#237;nicos &#40;EC&#41; fase <span class="elsevierStyleSmallCaps">iii</span> &#40;SOLO-1 y SOLO-2&#41;&#44; de dise&#241;o id&#233;ntico&#44; en un total de 1&#46;379 pacientes adultos con DA moderada a grave&#44; la administraci&#243;n de dupilumab 300<span class="elsevierStyleHsp" style=""></span>mg cada 2 semanas durante 16 semanas fue superior a placebo en el objetivo primario &#40;IGA de 0 o 1&#58; 38 y 36&#37; para dupilumab vs&#46; 10 y 8&#37; para placebo&#44; respectivamente&#41;<a class="elsevierStyleCrossRef" href="#bib0370"><span class="elsevierStyleSup">12</span></a>&#46; 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&#40;antagonizado por dupilumab&#41; e IL-13R&#945;1&#44; y el receptor se&#241;uelo IL-13R&#945;2&#44; que media la regulaci&#243;n end&#243;gena de IL-13&#46; Esta v&#237;a permite evaluar&#44; por lo tanto&#44; en qu&#233; medida la inhibici&#243;n de IL-4 puede ser redundante con respecto a IL-13 en la patog&#233;nesis de la enfermedad<a class="elsevierStyleCrossRef" href="#bib0405"><span class="elsevierStyleSup">19</span></a>&#46; En un EC fase <span class="elsevierStyleSmallCaps">ii</span>b con 204 pacientes adultos con DA moderada a grave&#44; la administraci&#243;n de tralokinumab a dosis de 300<span class="elsevierStyleHsp" style=""></span>mg cada 2 semanas durante 12 semanas logr&#243; una reducci&#243;n del EASI frente a placebo &#40;media de cambio ajustada respecto al valor basal de &#8722;15&#44;7 vs&#46; &#8722;10&#44;8&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;011&#41; y un mayor porcentaje de pacientes present&#243; un IGA 0-1 &#40;26&#44;7 vs&#46; 11&#44;8&#37;&#41;&#46; Estos resultados muestran tambi&#233;n una alta respuesta a placebo&#44; probablemente debido al uso concomitante de corticoides t&#243;picos en este EC&#46; Tambi&#233;n hubo una mejor&#237;a significativa en el SCORAD&#44; el <span class="elsevierStyleItalic">Dermatology Life Quality Index</span> y el prurito<a class="elsevierStyleCrossRef" href="#bib0410"><span class="elsevierStyleSup">20</span></a>&#46; En este momento est&#225;n en marcha EC de fase <span class="elsevierStyleSmallCaps">iii</span> de tralokinumab en adultos<a class="elsevierStyleCrossRef" href="#bib0415"><span class="elsevierStyleSup">21</span></a> y adolescentes<a class="elsevierStyleCrossRef" href="#bib0420"><span class="elsevierStyleSup">22</span></a>&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">Lebrikizumab es otro anticuerpo monoclonal dirigido frente a la IL-13&#46; Se une a la IL-13 soluble e inhibe su uni&#243;n al IL-4R&#945;<a class="elsevierStyleCrossRef" href="#bib0425"><span class="elsevierStyleSup">23</span></a>&#46; En un EC fase <span class="elsevierStyleSmallCaps">ii</span> en 209 pacientes adultos con DA moderada a grave&#44; el grupo tratado con lebrikizumab 125<span class="elsevierStyleHsp" style=""></span>mg cada 4 semanas present&#243; un mayor porcentaje de EASI-50 que el grupo tratado con placebo &#40;82&#44;4 vs&#46; 62&#44;3&#37;&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;026&#41;&#46; De nuevo&#44; hubo respuestas no despreciables en el grupo placebo&#44; que podr&#237;an atribuirse al uso concomitante de corticoides t&#243;picos<a class="elsevierStyleCrossRef" href="#bib0430"><span class="elsevierStyleSup">24</span></a>&#46; En este momento se encuentra activo un ensayo que eval&#250;a su eficacia a dosis de 250<span class="elsevierStyleHsp" style=""></span>mg cada 2 y 4 semanas<a class="elsevierStyleCrossRef" href="#bib0435"><span class="elsevierStyleSup">25</span></a>&#46;</p><p id="par0070" class="elsevierStylePara elsevierViewall">El bloqueo espec&#237;fico de la IL-13 tambi&#233;n ha sido evaluado en el asma&#44; con mejor&#237;as modestas para tralokinumab y lebrikizumab<a class="elsevierStyleCrossRefs" href="#bib0440"><span class="elsevierStyleSup">26&#44;27</span></a>&#46; Al igual que en la DA&#44; la respuesta podr&#237;a ser mayor en aquellos pacientes con concentraciones m&#225;s elevadas de marcadores relacionados con la IL-13<a class="elsevierStyleCrossRef" href="#bib0410"><span class="elsevierStyleSup">20</span></a>&#46; Sin embargo&#44; se necesitan EC en monoterapia para evaluar la utilidad del bloqueo exclusivo de IL-13&#46;</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Bloqueo de la inducci&#243;n a la respuesta Th2&#58; TSLP&#44; OX40L e IL-33</span><p id="par0075" class="elsevierStylePara elsevierViewall">El eje Th2 tambi&#233;n incluye la v&#237;a de la TSLP&#44; clave en la interacci&#243;n entre la epidermis y la activaci&#243;n inmune innata y adaptativa&#44; al derivar la respuesta inflamatoria a un fenotipo al&#233;rgico a trav&#233;s de la activaci&#243;n de las c&#233;lulas dendr&#237;ticas inmaduras&#44; que expresan OX40L&#44; lo que permite la polarizaci&#243;n hacia una respuesta Th2<a class="elsevierStyleCrossRef" href="#bib0450"><span class="elsevierStyleSup">28</span></a>&#46; De forma parecida&#44; IL-33&#44; producida por las c&#233;lulas epiteliales&#44; puede regular positivamente el eje TSLP-c&#233;lula dendr&#237;tica-OX40L&#44; participando en la inducci&#243;n y el mantenimiento de la respuesta Th2<a class="elsevierStyleCrossRefs" href="#bib0455"><span class="elsevierStyleSup">29&#44;30</span></a>&#46; La inhibici&#243;n de esta v&#237;a podr&#237;a ser interesante desde el punto de vista del tratamiento temprano&#44; debido a su participaci&#243;n en el inicio de la respuesta Th2&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">Tezepelumab es un anticuerpo monoclonal frente a TSLP&#44; recientemente evaluado en un EC fase <span class="elsevierStyleSmallCaps">ii</span>a&#44; sin presentar una eficacia superior a placebo a las 16 semanas<a class="elsevierStyleCrossRef" href="#bib0465"><span class="elsevierStyleSup">31</span></a>&#46; En este momento se encuentra en marcha otro EC de b&#250;squeda de dosis con tezepelumab &#40;NCT03809663&#41;&#46; Otra mol&#233;cula&#44; la MK-8226&#44; antagonista del receptor del TSLP&#44; fue evaluada en un EC fase <span class="elsevierStyleSmallCaps">i</span> a distintas dosis&#44; por v&#237;a IV&#44; con resultados que muestran un descenso significativo del EASI a dosis de 3<span class="elsevierStyleHsp" style=""></span>mg&#47;kg en comparaci&#243;n con placebo a las 12 semanas &#40;10&#44;20 vs&#46; 0&#44;38&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;015&#41;<a class="elsevierStyleCrossRef" href="#bib0470"><span class="elsevierStyleSup">32</span></a>&#46;</p><p id="par0085" class="elsevierStylePara elsevierViewall">Un anticuerpo monoclonal frente a OX40&#44; el GBR 830&#44; ha sido evaluado frente a placebo a dosis de 10<span class="elsevierStyleHsp" style=""></span>mg&#47;kg&#47;4<span class="elsevierStyleHsp" style=""></span>s IV durante 2 meses&#44; con resultados positivos<a class="elsevierStyleCrossRef" href="#bib0475"><span class="elsevierStyleSup">33</span></a>&#46; En este momento est&#225;n en marcha EC con otro inhibidor del OX40&#44; la mol&#233;cula KHK4093 &#40;NCT03096223 y NCT03703102&#41;&#44; as&#237; como con etokimab&#47;ANB020&#44; un anticuerpo monoclonal anti-IL-33 &#40;NCT03533751&#41;&#46;</p></span></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Antagonismo de la respuesta celular Th22</span><p id="par0090" class="elsevierStylePara elsevierViewall">Los linfocitos Th22 son los principales productores de IL-22 y participan tanto en las formas agudas como cr&#243;nicas de la DA&#46; La IL-22 puede aumentar la disfunci&#243;n de barrera&#44; inducir hiperplasia epid&#233;rmica e inhibir prote&#237;nas clave en la queratinizaci&#243;n normal&#44; como la filagrina<a class="elsevierStyleCrossRef" href="#bib0480"><span class="elsevierStyleSup">34</span></a>&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">En un EC fase <span class="elsevierStyleSmallCaps">ii</span>a&#44; el uso de fezakinumab &#40;ILV-094&#41;&#44; un anti-IL-22&#44; a dosis de 300<span class="elsevierStyleHsp" style=""></span>mg cada 2 semanas&#44; consigui&#243; una mejor&#237;a&#44; aunque no significativa frente a placebo en la disminuci&#243;n del SCORAD en pacientes con DA moderada a grave&#46; El suban&#225;lisis de pacientes con DA grave s&#237; mostr&#243; diferencias significativas en la reducci&#243;n del <span class="elsevierStyleItalic">Body Surface Area</span> &#40;BSA&#41; y el IGA<a class="elsevierStyleCrossRef" href="#bib0485"><span class="elsevierStyleSup">35</span></a>&#46; El beneficio de este f&#225;rmaco podr&#237;a estar limitado a pacientes con peor respuesta al bloqueo de la v&#237;a Th2 y con mayor expresi&#243;n de Th22<a class="elsevierStyleCrossRef" href="#bib0490"><span class="elsevierStyleSup">36</span></a>&#44; aunque la evidencia hasta la fecha es limitada&#46;</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Antagonismo de la respuesta celular Th17</span><p id="par0100" class="elsevierStylePara elsevierViewall">Como se ha mencionado&#44; en la etapa cr&#243;nica de la DA y en determinados grupos de pacientes se mantiene una respuesta Th2 y Th22&#44; pero existe una activaci&#243;n paralela del eje Th1&#47;Th17<a class="elsevierStyleCrossRef" href="#bib0495"><span class="elsevierStyleSup">37</span></a>&#46; Recientemente&#44; se ha estudiado el bloqueo de la IL-17A y la IL-17C&#46; Aunque los datos sobre la inhibici&#243;n de este eje en la DA son a&#250;n muy preliminares&#44; resulta interesante su desarrollo&#44; dado el potencial terap&#233;utico en determinados subfenotipos de DA&#46;</p><p id="par0105" class="elsevierStylePara elsevierViewall">Secukinumab&#44; un inhibidor selectivo de la IL-17A&#44; aprobado en la psoriasis&#44; ha sido evaluado recientemente en un EC de fase <span class="elsevierStyleSmallCaps">ii</span> en la DA &#40;NCT02594098&#41;&#44; con la pauta de inducci&#243;n empleada en la psoriasis y con un mantenimiento a dosis de 300<span class="elsevierStyleHsp" style=""></span>mg&#47;4 semanas o intensificado 300<span class="elsevierStyleHsp" style=""></span>mg&#47;2 semanas&#46; Los resultados se encuentran pendientes de publicaci&#243;n<a class="elsevierStyleCrossRef" href="#bib0500"><span class="elsevierStyleSup">38</span></a>&#46;</p><p id="par0110" class="elsevierStylePara elsevierViewall">Por otro lado&#44; est&#225;n en marcha estudios &#40;NCT03568071&#44; NCT03689829&#44; NCT03864627&#41; con un anticuerpo dirigido frente a la IL-17C&#44; MOR106&#44; que podr&#237;a mediar una disminuci&#243;n en los niveles de IgE y citocinas Th2<a class="elsevierStyleCrossRef" href="#bib0505"><span class="elsevierStyleSup">39</span></a>&#46;</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Bloqueo de la v&#237;a IL-31 y OSMR&#946; &#40;se&#241;alizaci&#243;n del prurito&#41;</span><p id="par0115" class="elsevierStylePara elsevierViewall">La IL-31 es una citocina producida principalmente por los linfocitos Th2&#44; muy relacionada con el prurito&#44; en distintos tipos celulares&#44; incluyendo las neuronas perif&#233;ricas<a class="elsevierStyleCrossRefs" href="#bib0510"><span class="elsevierStyleSup">40&#44;41</span></a>&#46; La IL-31 se une a un receptor heterodim&#233;rico compuesto por el receptor &#945; de la IL-31 &#40;IL-31R&#945;&#41; y el receptor &#946; de oncastatina M &#40;OSMR&#946;&#41;&#46; Su bloqueo&#44; por tanto&#44; podr&#237;a tambi&#233;n romper el c&#237;rculo vicioso de prurito-rascado y el compromiso de la funci&#243;n de barrera epid&#233;rmica&#46;</p><p id="par0120" class="elsevierStylePara elsevierViewall">Nemolizumab bloquea el receptor &#945; de la IL-31 &#40;IL-31R&#945;&#41;&#46; Hasta la fecha&#44; un EC fase <span class="elsevierStyleSmallCaps">ii</span> controlado con placebo en adultos tratados con nemolizumab &#40;dosis de 0&#44;1<span class="elsevierStyleHsp" style=""></span>mg&#47;kg&#44; 0&#44;5<span class="elsevierStyleHsp" style=""></span>mg&#47;kg o 2<span class="elsevierStyleHsp" style=""></span>mg&#47;kg cada 4 semanas durante 12 semanas&#41; ha demostrado reducciones del prurito&#59; sin embargo&#44; la mejor&#237;a en escalas cl&#237;nicas no alcanz&#243; la significaci&#243;n estad&#237;stica<a class="elsevierStyleCrossRefs" href="#bib0510"><span class="elsevierStyleSup">40&#44;42</span></a>&#46; Nemolizumab podr&#237;a ser efectivo en la reducci&#243;n del prurito&#44; as&#237; como en la actividad cotidiana y la productividad laboral<a class="elsevierStyleCrossRef" href="#bib0525"><span class="elsevierStyleSup">43</span></a>&#44; con un perfil de seguridad adecuado&#46; En este momento est&#225; pendiente la finalizaci&#243;n de un EC de b&#250;squeda de dosis &#40;NCT03100344&#41;&#46;</p><p id="par0125" class="elsevierStylePara elsevierViewall">El EC fase <span class="elsevierStyleSmallCaps">i</span> &#40;NCT01614756&#41; que investigaba el uso de un anti-IL-31 &#40;BMS-981164&#41; finaliz&#243; en una etapa temprana y no se han publicado los resultados&#46; A&#250;n se desconoce&#44; por tanto&#44; si los efectos del bloqueo sobre la IL-31 ser&#237;an solo sintom&#225;ticos sobre el prurito&#44; dado que estos no se han asociado a mejoras significativas en los &#237;ndices de inflamaci&#243;n cut&#225;nea&#46;</p><p id="par0130" class="elsevierStylePara elsevierViewall">Por otro lado&#44; se ha realizado un EC fase <span class="elsevierStyleSmallCaps">i</span>a&#47;<span class="elsevierStyleSmallCaps">i</span>b con KPL-716&#44; un anticuerpo anti-OSMR&#946; que ha demostrado una mejor&#237;a del EASI y en las escalas de prurito comparado con placebo<a class="elsevierStyleCrossRef" href="#bib0530"><span class="elsevierStyleSup">44</span></a>&#46;</p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Antagonismo de la IgE</span><p id="par0135" class="elsevierStylePara elsevierViewall">Omalizumab&#44; un anti-IgE&#44; aprobado en el tratamiento del asma&#44; ha sido evaluado en un metaan&#225;lisis&#44; sin evidencia de efectividad global en adultos con DA<a class="elsevierStyleCrossRef" href="#bib0535"><span class="elsevierStyleSup">45</span></a>&#46; Est&#225; en investigaci&#243;n su uso en poblaci&#243;n pedi&#225;trica &#40;NCT02300701&#41;&#46;</p></span></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Mol&#233;culas peque&#241;as</span><p id="par0140" class="elsevierStylePara elsevierViewall">Se incluyen agentes de administraci&#243;n oral que generan una reducci&#243;n amplia&#44; menos espec&#237;fica&#44; de la liberaci&#243;n de mediadores&#46; Esta estrategia tiene ventajas en la DA&#44; ya que&#44; a diferencia de la psoriasis&#44; no existe evidencia de la implicaci&#243;n fundamental de una mol&#233;cula clave en la patog&#233;nesis de la enfermedad&#46; Por el contrario&#44; esta menor especificidad podr&#237;a relacionarse con potenciales problemas de seguridad&#46;</p><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Inhibici&#243;n de la v&#237;a de se&#241;alizaci&#243;n JAK-STAT</span><p id="par0145" class="elsevierStylePara elsevierViewall">En este momento existen 4 inhibidores de JAK por v&#237;a oral en estudio<a class="elsevierStyleCrossRef" href="#bib0365"><span class="elsevierStyleSup">11</span></a>&#46; Baricitinib antagoniza a JAK 1 &#40;asociada con la modulaci&#243;n de las citocinas IL-4&#44; IL-6&#44; IL-10&#44; IL-13&#44; IL-31 e IFN-&#947;&#41; y JAK2 &#40;que modula las citocinas IL-5&#44; IL-6&#44; IL-23&#44; IL-31 e IFN-&#947;&#41;<a class="elsevierStyleCrossRefs" href="#bib0365"><span class="elsevierStyleSup">11&#44;46</span></a>&#46; En el primer EC fase <span class="elsevierStyleSmallCaps">ii</span> la administraci&#243;n de baricitinib&#44; a dosis de 4<span class="elsevierStyleHsp" style=""></span>mg una vez al d&#237;a por v&#237;a oral&#44; en pacientes con DA moderada a grave&#44; se asoci&#243; a una mayor consecuci&#243;n de EASI-50 en comparaci&#243;n con placebo &#40;61 vs&#46; 37&#37;&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;027&#41; a las 16 semanas&#44; con buena tolerancia&#46; Entre los efectos adversos reportados se encuentra la elevaci&#243;n asintom&#225;tica de la creatina cinasa&#44; pero no hubo casos de eventos tromb&#243;ticos ni de herpes z&#243;ster<a class="elsevierStyleCrossRef" href="#bib0545"><span class="elsevierStyleSup">47</span></a>&#46;</p><p id="par0150" class="elsevierStylePara elsevierViewall">Upadacitinib &#40;ABT-494&#41; y abrocitinib &#40;PF-04965842&#41; son inhibidores selectivos de JAK1&#44; de los que se dispone de resultados iniciales prometedores&#46; Un EC fase <span class="elsevierStyleSmallCaps">ii</span>b evalu&#243; el uso de upadacitinib a dosis de 7&#44;5&#47;15&#47;30<span class="elsevierStyleHsp" style=""></span>mg frente a placebo durante 16 semanas&#46; La reducci&#243;n en el EASI frente al valor basal fue del 74&#47;62&#47;39&#37; para las dosis de 30&#47;15&#47;7&#44;5<span class="elsevierStyleHsp" style=""></span>mg&#44; respectivamente&#44; mejor&#237;as que podr&#237;an ser similares a las obtenidas con dupilumab&#46; En este momento se encuentra activo un EC fase <span class="elsevierStyleSmallCaps">iii</span> de evaluaci&#243;n de la eficacia de upadacitinib en adultos y adolescentes &#40;NCT03607422&#41;&#46; Otro EC fase <span class="elsevierStyleSmallCaps">ii</span>b evalu&#243; el uso de abrocitinib a dosis de 10&#47;30&#47;100&#47;200<span class="elsevierStyleHsp" style=""></span>mg al d&#237;a frente a placebo&#44; con reducciones del EASI que solo fueron significativas para las dosis de 200<span class="elsevierStyleHsp" style=""></span>mg &#40;82&#44;6&#37;&#59; p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#41; y de 100<span class="elsevierStyleHsp" style=""></span>mg &#40;59&#37;&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;009&#41; frente a placebo &#40;35&#44;2&#37;&#41;<a class="elsevierStyleCrossRef" href="#bib0540"><span class="elsevierStyleSup">46</span></a>&#46; Est&#225;n en marcha numerosos EC fase <span class="elsevierStyleSmallCaps">iii</span> de abrocitinib a dosis de 100 y 200<span class="elsevierStyleHsp" style=""></span>mg frente a placebo &#40;NCT03349060&#44; NCT03575871&#44; NCT03627767 y NCT03422822&#41;&#44; as&#237; como un EC fase <span class="elsevierStyleSmallCaps">iii</span> comparado con dupilumab &#40;NCT03720470&#41;&#46; Por &#250;ltimo&#44; ASN002 es un inhibidor dual de las v&#237;as JAK y SYK&#46; La inhibici&#243;n PAN-JAK afecta a la se&#241;alizaci&#243;n de diversas citocinas en la DA &#40;IL-4&#44; IL-13&#44; IL-31 e IL-33&#41;&#44; mientras que la inhibici&#243;n de SYK suprime la se&#241;alizaci&#243;n de citocinas proinflamatorias &#40;IL-1&#946;&#44; IL-10&#44; IL-17&#41;&#46; En el primer EC de fase <span class="elsevierStyleSmallCaps">i</span>b de ASNN002&#44; el porcentaje de pacientes que alcanz&#243; un EASI-50 a los 28 d&#237;as fue superior a placebo para las dosis de 40 y 80<span class="elsevierStyleHsp" style=""></span>mg<a class="elsevierStyleCrossRef" href="#bib0550"><span class="elsevierStyleSup">48</span></a>&#46;</p><p id="par0155" class="elsevierStylePara elsevierViewall">En la actualidad&#44; est&#225;n activos EC de fase <span class="elsevierStyleSmallCaps">iii</span> con estos 4 f&#225;rmacos&#46;</p></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Antagonismo de la fosfodiesterasa 4</span><p id="par0160" class="elsevierStylePara elsevierViewall">Recientemente&#44; se ha evaluado el tratamiento con inhibidores de la fosfodiesterasa &#40;PDE4&#41;&#44; de administraci&#243;n t&#243;pica y oral&#46; En la DA la actividad de la PDE4 en distintas c&#233;lulas inflamatorias est&#225; aumentada en comparaci&#243;n con la piel sana&#46; La PDE degrada el AMPc&#44; que normalmente inhibe la producci&#243;n de diversas citocinas proinflamatorias&#44; como la IL-4&#44; la IL-31 y la PGE-2&#46; El antagonismo de la PDE4 act&#250;a de forma amplia y no espec&#237;fica&#44; ya que eleva el AMPc intracelular y permite reducir la liberaci&#243;n de citocinas y quimiocinas<a class="elsevierStyleCrossRef" href="#bib0555"><span class="elsevierStyleSup">49</span></a>&#46;</p><p id="par0165" class="elsevierStylePara elsevierViewall">En un estudio fase <span class="elsevierStyleSmallCaps">ii</span>&#44; apremilast 40<span class="elsevierStyleHsp" style=""></span>mg&#47;12<span class="elsevierStyleHsp" style=""></span>h logr&#243; una reducci&#243;n del EASI superior a placebo &#40;31&#44;57 vs&#46; 10&#44;98&#37;&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;034&#41;&#46; Sin embargo&#44; no hubo diferencias estad&#237;sticamente significativas en el EASI-50 ni en el prurito<a class="elsevierStyleCrossRef" href="#bib0560"><span class="elsevierStyleSup">50</span></a>&#46; En este momento no hay nuevos EC con apremilast en DA&#46;</p></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Antagonismo del receptor de la histamina 4</span><p id="par0170" class="elsevierStylePara elsevierViewall">En los &#250;ltimos a&#241;os se ha estudiado el papel del antagonismo del receptor de la histamina 4&#44; que no solo lograr&#237;a un efecto antipruriginoso&#44; sino tambi&#233;n antiinflamatorio&#44; dado que la activaci&#243;n del receptor en el queratinocito interfiere en su proliferaci&#243;n y en la funci&#243;n de barrera<a class="elsevierStyleCrossRef" href="#bib0565"><span class="elsevierStyleSup">51</span></a>&#46;</p><p id="par0175" class="elsevierStylePara elsevierViewall">Un EC fase <span class="elsevierStyleSmallCaps">ii</span>a con un antagonista del receptor de la histamina 4&#44; JNJ-39758979&#44; mostr&#243; diferencias significativas en la reducci&#243;n del prurito&#44; no as&#237; del EASI&#46; Sin embargo&#44; este EC fue interrumpido debido a 2 casos de neutropenia grave<a class="elsevierStyleCrossRef" href="#bib0570"><span class="elsevierStyleSup">52</span></a>&#46; Recientemente se han publicado los resultados de EC en fase <span class="elsevierStyleSmallCaps">ii</span> con otro antagonista del receptor de la histamina 4&#44; ZPL-3893787&#44; con disminuciones significativas frente a placebo del EASI y&#44; en cambio&#44; no significativas en el prurito<a class="elsevierStyleCrossRef" href="#bib0575"><span class="elsevierStyleSup">53</span></a>&#46;</p></span><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Bloqueo del receptor de la neuroquinina 1</span><p id="par0180" class="elsevierStylePara elsevierViewall">La sustancia P&#44; mediadora del prurito&#44; se une principalmente al receptor de la neuroquinina 1&#44; que se expresa tanto en el sistema nervioso central como en la piel&#46; En este sentido&#44; antagonistas del receptor de la neuroquinina 1 de administraci&#243;n oral&#44; como aprepitant&#44; podr&#237;an mejorar el prurito<a class="elsevierStyleCrossRef" href="#bib0580"><span class="elsevierStyleSup">54</span></a>&#46; Sin embargo&#44; su uso en la DA no parece aportar beneficios<a class="elsevierStyleCrossRef" href="#bib0585"><span class="elsevierStyleSup">55</span></a>&#46; Otros inhibidores del receptor de la neuroquinina 1&#44; tradipitant y serlopitant&#44; est&#225;n siendo evaluados&#44; aunque tambi&#233;n con resultados modestos&#46;</p><p id="par0185" class="elsevierStylePara elsevierViewall">En la <a class="elsevierStyleCrossRef" href="#tbl0005">tabla 1</a> se resumen los principales EC de los nuevos f&#225;rmacos sist&#233;micos&#44; y en las <a class="elsevierStyleCrossRefs" href="#fig0005">figuras 1 y 2</a> se se&#241;alan sus dianas terap&#233;uticas&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia></span></span><span id="sec0085" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Tratamientos t&#243;picos</span><p id="par0190" class="elsevierStylePara elsevierViewall">De forma independiente a los avances en los f&#225;rmacos sist&#233;micos&#44; las terapias t&#243;picas siguen siendo esenciales tanto en la reparaci&#243;n de la funci&#243;n de barrera como en el transporte de mol&#233;culas antiinflamatorias&#46; M&#225;s all&#225; de los emolientes&#44; los corticoides y los inhibidores de la calcineurina&#44; se han desarrollado nuevas mol&#233;culas de peque&#241;o tama&#241;o que permiten considerar su uso t&#243;pico&#46;</p><span id="sec0090" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Inhibidores t&#243;picos de la se&#241;alizaci&#243;n JAK&#47;STAT</span><p id="par0195" class="elsevierStylePara elsevierViewall">En el momento actual se encuentran en investigaci&#243;n inhibidores t&#243;picos de la v&#237;a JAK&#47;STAT&#46; Entre estos&#44; tofacitinib t&#243;pico al 2&#37; y ruxolitinib al 1&#44;5&#37; parecen tener eficacia en la reducci&#243;n del EASI y del prurito<a class="elsevierStyleCrossRef" href="#bib0540"><span class="elsevierStyleSup">46</span></a>&#46; En un EC japon&#233;s&#44; delgocitinib&#44; un inhibidor PAN-JAK&#44; tambi&#233;n ha demostrado mejor&#237;as del EASI superiores al veh&#237;culo&#44; sin efectos adversos significativos<a class="elsevierStyleCrossRef" href="#bib0590"><span class="elsevierStyleSup">56</span></a>&#46;</p></span><span id="sec0095" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Inhibidores t&#243;picos de la PDE4</span><p id="par0200" class="elsevierStylePara elsevierViewall">El crisaborol t&#243;pico al 2&#37; es el primer inhibidor de la PDE4 aprobado en adultos y ni&#241;os mayores de 2 a&#241;os con DA leve a moderada&#46; En los EC de fase <span class="elsevierStyleSmallCaps">iii</span> se demostr&#243; una eficacia estad&#237;sticamente significativa en t&#233;rminos de IGA-0 &#40;51&#44;7&#37;&#41; e IGA-1 &#40;48&#44;5&#37;&#41; frente a veh&#237;culo &#40;40&#44;6 y 29&#44;7&#37;&#44; respectivamente&#41; a las 4 semanas<a class="elsevierStyleCrossRef" href="#bib0595"><span class="elsevierStyleSup">57</span></a>&#46; Se han descrito reacciones adversas leves&#44; como dolor o quemaz&#243;n en el lugar de aplicaci&#243;n&#46; Est&#225;n en marcha EC con otros inhibidores de la PDE4&#44; como las mol&#233;culas E6005 y AN2898<a class="elsevierStyleCrossRef" href="#bib0600"><span class="elsevierStyleSup">58</span></a>&#46;</p></span><span id="sec0100" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Ominagan</span><p id="par0205" class="elsevierStylePara elsevierViewall">La menor producci&#243;n de p&#233;ptidos antimicrobianos en la DA facilita la colonizaci&#243;n y la infecci&#243;n microbiana e incrementa la respuesta inflamatoria&#46; En este sentido&#44; se ha desarrollado ominagan en gel&#44; un p&#233;ptido antimicrobiano evaluado en 2 EC fase <span class="elsevierStyleSmallCaps">ii</span>&#59; aunque se desconocen sus resultados&#44; existen publicaciones que indican buena tolerancia<a class="elsevierStyleCrossRef" href="#bib0605"><span class="elsevierStyleSup">59</span></a>&#46;</p></span><span id="sec0105" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0130">Tapinarof</span><p id="par0210" class="elsevierStylePara elsevierViewall">Tapinarof es un antiinflamatorio no esteroideo que act&#250;a como agonista del receptor de hidrocarburo arilo&#44; pudiendo mejorar la funci&#243;n de barrera y limitar la respuesta Th2<a class="elsevierStyleCrossRef" href="#bib0610"><span class="elsevierStyleSup">60</span></a>&#46; En un EC fase <span class="elsevierStyleSmallCaps">ii</span> el uso de tapinarof al 1&#37; 2 veces al d&#237;a demostr&#243; diferencias significativas en el IGA 0-1 y en la reducci&#243;n del EASI&#44; el SCORAD y el BSA frente al veh&#237;culo&#44; con buena tolerancia y desarrollo de 2 casos de dermatitis de contacto sobre 165 pacientes tratados<a class="elsevierStyleCrossRef" href="#bib0615"><span class="elsevierStyleSup">61</span></a>&#46;</p></span><span id="sec0110" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0135">PR022 &#40;&#225;cido hipocloroso&#41;</span><p id="par0215" class="elsevierStylePara elsevierViewall">En una serie de casos de pacientes con DA&#44; el uso al 0&#44;008 y 0&#44;002&#37; de &#225;cido hipocloroso t&#243;pico&#44; en hidrogel&#44; se asoci&#243; a una reducci&#243;n del prurito&#46; Se cree que el &#225;cido hipocloroso podr&#237;a disminuir las concentraciones de distintas citocinas&#44; como el TNF-&#945;&#44; la IL-2&#44; el IFN-&#947; o la histamina<a class="elsevierStyleCrossRef" href="#bib0605"><span class="elsevierStyleSup">59</span></a>&#46; Est&#225; en marcha un EC fase <span class="elsevierStyleSmallCaps">ii</span> en adultos con DA leve-moderada &#40;NCT03351777&#41;&#46;</p></span><span id="sec0115" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0140">SP14019&#47;Cyclatop</span><p id="par0220" class="elsevierStylePara elsevierViewall">SP14019&#47;Cyclatop es una formulaci&#243;n t&#243;pica en espray de ciclosporina al 5&#37;&#44; evaluada en un EC fase <span class="elsevierStyleSmallCaps">ii</span> en pacientes<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>2 a&#241;os &#40;NCT02865356&#41;&#46; Sus resultados fueron presentados en el congreso europeo de dermatolog&#237;a del 2018&#44; con mejor&#237;as significativas del EASI y el IGA frente al veh&#237;culo a las 4 semanas&#44; con buena tolerancia y escasa absorci&#243;n sist&#233;mica<a class="elsevierStyleCrossRef" href="#bib0620"><span class="elsevierStyleSup">62</span></a>&#46;</p><p id="par0225" class="elsevierStylePara elsevierViewall">En la <a class="elsevierStyleCrossRef" href="#tbl0010">tabla 2</a> se resumen los f&#225;rmacos t&#243;picos en v&#237;as de investigaci&#243;n&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia></span></span></span><span id="sec0120" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0145">Conclusiones</span><p id="par0230" class="elsevierStylePara elsevierViewall">En los &#250;ltimos a&#241;os&#44; el mayor conocimiento de la patogenia de la DA&#44; m&#225;s all&#225; del eje Th2&#44; ha permitido el desarrollo de nuevos f&#225;rmacos&#44; t&#243;picos y sist&#233;micos &#8212;biol&#243;gicos y mol&#233;culas peque&#241;as&#8212;&#44; dirigidos frente a elementos clave de la inflamaci&#243;n&#46; Aunque la psoriasis representa una referencia de medicina traslacional por sus similitudes con la DA&#44; los resultados todav&#237;a est&#225;n lejos de los obtenidos en aquella enfermedad&#46; En la actualidad&#44; todav&#237;a est&#225; en discusi&#243;n si la mejor estrategia pasa por la inhibici&#243;n de elementos concretos del proceso inflamatorio a trav&#233;s de anticuerpos monoclonales &#8212;por ejemplo&#44; dupilumab&#8212; o mol&#233;culas m&#225;s transversales y menos espec&#237;ficas &#8212;por ejemplo&#44; upadicitinib&#8212;&#46; El avance en la investigaci&#243;n de las nuevas terapias y la estratificaci&#243;n en los distintos subtipos o subfenotipos de DA en los pr&#243;ximos a&#241;os parece esencial para llegar a tratamientos efectivos&#44; a largo plazo&#44; con un perfil de seguridad aceptable&#44; especialmente en las formas moderadas a graves&#46;</p></span><span id="sec0125" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0150">Conflicto de intereses</span><p id="par0235" class="elsevierStylePara elsevierViewall">J&#46;M&#46; Carrascosa ha recibido honorarios como ponente y asesor para Sanofi y como IP&#47;SI en ensayos cl&#237;nicos para Sanofi&#44; Lilly&#44; Leo-Pharma&#44; Pfizer&#44; Amgen&#46; M&#46; Munera-Campos ha participado y recibido honorarios como SI en ensayos cl&#237;nicos para Lilly&#44; Leo-Pharma y Pfizer&#46;</p></span></span>"
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          "titulo" => "Tratamientos sist&#233;micos"
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              "titulo" => "F&#225;rmacos biol&#243;gicos"
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                  "identificador" => "sec0025"
                  "titulo" => "Antagonismo de la respuesta celular Th2 &#40;IL-4 e IL-13&#41;"
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                    0 => array:2 [
                      "identificador" => "sec0030"
                      "titulo" => "Bloqueo de la v&#237;a IL-4&#47;IL-13"
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                    1 => array:2 [
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                      "titulo" => "Bloqueo de la inducci&#243;n a la respuesta Th2&#58; TSLP&#44; OX40L e IL-33"
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                1 => array:2 [
                  "identificador" => "sec0040"
                  "titulo" => "Antagonismo de la respuesta celular Th22"
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                  "titulo" => "Antagonismo de la respuesta celular Th17"
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                  "titulo" => "Bloqueo de la v&#237;a IL-31 y OSMR&#946; &#40;se&#241;alizaci&#243;n del prurito&#41;"
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                4 => array:2 [
                  "identificador" => "sec0055"
                  "titulo" => "Antagonismo de la IgE"
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              "titulo" => "Mol&#233;culas peque&#241;as"
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                  "identificador" => "sec0065"
                  "titulo" => "Inhibici&#243;n de la v&#237;a de se&#241;alizaci&#243;n JAK-STAT"
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                1 => array:2 [
                  "identificador" => "sec0070"
                  "titulo" => "Antagonismo de la fosfodiesterasa 4"
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                2 => array:2 [
                  "identificador" => "sec0075"
                  "titulo" => "Antagonismo del receptor de la histamina 4"
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                  "titulo" => "Bloqueo del receptor de la neuroquinina 1"
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              "titulo" => "Tratamientos t&#243;picos"
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                  "titulo" => "Inhibidores t&#243;picos de la se&#241;alizaci&#243;n JAK&#47;STAT"
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                1 => array:2 [
                  "identificador" => "sec0095"
                  "titulo" => "Inhibidores t&#243;picos de la PDE4"
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                  "titulo" => "Ominagan"
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                3 => array:2 [
                  "identificador" => "sec0105"
                  "titulo" => "Tapinarof"
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                4 => array:2 [
                  "identificador" => "sec0110"
                  "titulo" => "PR022 &#40;&#225;cido hipocloroso&#41;"
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                  "identificador" => "sec0115"
                  "titulo" => "SP14019&#47;Cyclatop"
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          "titulo" => "Conflicto de intereses"
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    "fechaRecibido" => "2019-07-05"
    "fechaAceptado" => "2019-11-04"
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          "palabras" => array:6 [
            0 => "Dermatitis at&#243;pica"
            1 => "Patogenia"
            2 => "Biol&#243;gicos"
            3 => "Dupilumab"
            4 => "JAK"
            5 => "Tratamiento t&#243;pico"
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          "palabras" => array:6 [
            0 => "Atopic dermatitis"
            1 => "Pathogenesis"
            2 => "Biologics"
            3 => "Dupilumab"
            4 => "JAK"
            5 => "Topical treatment"
          ]
        ]
      ]
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        "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">La dermatitis at&#243;pica es la dermatosis inflamatoria m&#225;s frecuente y hasta un 20&#37; de los casos pueden clasificarse como moderados a graves&#46; En los &#250;ltimos a&#241;os se ha producido un avance en el conocimiento de la patogenia&#44; centrada en la v&#237;a Th2&#44; pero con una participaci&#243;n marcada de la v&#237;a Th22 y de los ejes Th1 y Th17&#44; de la disfunci&#243;n de la barrera epid&#233;rmica&#44; el prurito y la se&#241;alizaci&#243;n JAK&#47;STAT&#46; Este progreso ha condicionado el desarrollo de nuevas terapias sist&#233;micas&#44; entre las que destacan f&#225;rmacos biol&#243;gicos dirigidos frente a la IL-4&#47;13&#44; como dupilumab&#44; tralokinumab y lebrikizumab&#44; pero tambi&#233;n mol&#233;culas peque&#241;as&#44; como los inhibidores de JAK&#44; entre los que se incluyen baricitinib&#44; upadicitinib y abrocitinib&#46; Entre las innovaciones en los tratamientos t&#243;picos se incluyen los inhibidores de la PDE4 y de JAK&#47;STAT&#46; Este art&#237;culo repasa los principales avances terap&#233;uticos en dermatitis at&#243;pica&#44; para los que son esenciales la caracterizaci&#243;n de los subtipos cl&#237;nicos y moleculares clave en su patog&#233;nesis&#46;</p></span>"
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        "resumen" => "<span id="abst0015" class="elsevierStyleSection elsevierViewall"><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Atopic dermatitis is the most common inflammatory skin disease and up to 20&#37; of cases can be classified as moderate to severe&#46; Our understanding of the pathogenesis of this disease has improved in recent years&#46; The process is primarily driven by the Th2 pathway&#44; but with significant contributions from the Th22 pathway&#44; the Th1 and Th17 axes&#44; epidermal barrier dysfunction&#44; pruritus&#44; and JAK&#47;STAT signaling&#46; Advances in our understanding of the pathogenesis of atopic dermatitis have led to the development of new systemic treatments&#46; Of particular note are biologic agents targeting IL-4 and IL-13 &#40;e&#46; g&#46;&#44; dupilumab&#44; tralokinumab&#44; and lebrikizumab&#41; and small molecules&#44; such as JAK inhibitors &#40;e&#46; g&#46;&#44; baricitinib&#44; upadacitinib&#44; and abrocitinib&#41;&#46; Novel topical treatments include phosphodiesterase 4 and JAK&#47;STAT inhibitors&#46; In this article&#44; we review the main advances in the treatment of atopic dermatitis&#46; Characterization of clinical and molecular phenotypes with a key pathogenic role is essential for driving these advances&#46;</p></span>"
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          "es" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">F&#225;rmacos biol&#243;gicos y dianas espec&#237;ficas en la patogenia de la dermatitis at&#243;pica&#46;</p> <p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">IgE&#58; inmunoglobulina E&#59; IL&#58; interleucina&#59; OSMR&#946;&#58; receptor &#946; oncostatina M&#59; Th&#58; &#40;linfocito&#41; T helper&#59; TSLP&#58; thymic stromal lymphopoietin&#46;</p>"
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          "es" => "<p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">F&#225;rmacos mol&#233;culas peque&#241;as y dianas espec&#237;ficas en la patogenia de la dermatitis at&#243;pica&#46;</p> <p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">AC&#58; <span class="elsevierStyleItalic">adenylyl cyclase&#59;</span> AMPc&#58; adenos&#237;n-monofosfato c&#237;clico&#59; ATP&#58; adenos&#237;n trifosfato&#59; CREB&#58; <span class="elsevierStyleItalic">cAMP response element-binging protein&#59;</span> DGLA&#58; &#225;cido dihomo-&#947;-linol&#233;nico&#59; H4R&#58; receptor de la histamina 4&#59; IL&#58; interleucina&#59; JAK&#58; <span class="elsevierStyleItalic">Janus kinase&#59;</span> &#954;OR&#58; receptor &#954;-opioide&#59; NF-&#954;B&#58; n<span class="elsevierStyleItalic">uclear factor kappa-light-chain-enhancer of activated B cells&#59;</span> NFAT&#58; <span class="elsevierStyleItalic">nuclear factor of activated T-cells&#59;</span> NK-1R&#58; receptor de la neuroquinina 1&#59; PDE4&#58; fosfodiesterasa 4&#59; PGD1&#58; prostaglandina D1&#59; PGD2&#58; prostaglandina D2&#59; PGE1&#58; prostaglandina E1&#59; PKA&#58; <span class="elsevierStyleItalic">protein kinase A&#59;</span> STAT&#58; <span class="elsevierStyleItalic">signal transducer and activator of transcription&#59;</span> Th&#58; &#40;linfocito&#41; T <span class="elsevierStyleItalic">helper&#59;</span> TSLP&#58; <span class="elsevierStyleItalic">thymic stromal lymphopoietin&#59;</span> TYK&#58; <span class="elsevierStyleItalic">tyrosine-kinase&#46;</span></p>"
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            "rol" => "short"
          ]
        ]
        "tabla" => array:3 [
          "leyenda" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">BSA&#58; Body Surface Area&#59; CsA&#58; ciclosporina A&#59; DA&#58; dermatitis at&#243;pica&#59; DGLA&#58; &#225;cido dihomo-&#947;-linoleico&#59; DLQI&#58; <span class="elsevierStyleItalic">Dermatology Life Quality Index&#59; GISS&#58; Global Individual Signs Score&#59;</span> DU&#58; dosis &#250;nica&#59; EASI&#58; <span class="elsevierStyleItalic">Eczema Area and Severity Index&#59;</span> H4R&#58; receptor de la histamina 4&#59; IGA&#58; <span class="elsevierStyleItalic">Investigator Global Assessment&#59;</span> IL&#58; interleucina&#59; IV&#58; intravenoso&#59; JAK&#58; <span class="elsevierStyleItalic">Janus kinase&#59;</span> kOR&#58; receptor opioide kappa&#59; NKR1&#58; receptor de la neuroquinina 1&#59; PDE4&#58; fosfodiesterasa 4&#59; SC&#58; subcut&#225;neo&#59; SCORAD&#58; <span class="elsevierStyleItalic">SCORing Atopic Dermatitis&#59;</span> TH&#58; &#40;linfocito&#41; T <span class="elsevierStyleItalic">helper&#59;</span> TSLP&#58; <span class="elsevierStyleItalic">thymic stromal lymphopoietin&#59;</span> TYK&#58; <span class="elsevierStyleItalic">tyrosine-kinase&#59;</span> VO&#58; v&#237;a oral&#46;</p><p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Los datos mencionados espec&#237;ficamente en la tabla pertenecen a los ensayos cl&#237;nicos &#40;ID&#41; se&#241;alados mediante subrayado&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">F&#225;rmaco&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Diana&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">V&#237;a administraci&#243;n&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Gravedad&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Fase&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Estado&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Intervenci&#243;n&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Eficacia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Seguridad&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Ensayos cl&#237;nicos &#40;ID&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="10" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">F&#225;rmacos biol&#243;gicos</span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="10" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Antagonismo del eje TH2</span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="10" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Antagonismo espec&#237;fico de IL-4&#47;IL-13</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Dupilumab&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">IL-4&#44; IL-13 &#40;IL-4R&#945;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">SC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Moderada a grave&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">III<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Completado&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Aleatorizaci&#243;n 1&#58;1&#58;1 &#40;dupilumab 300<span class="elsevierStyleHsp" style=""></span>mg&#47;7<span class="elsevierStyleHsp" style=""></span>d vs&#46; 300<span class="elsevierStyleHsp" style=""></span>mg&#47;15<span class="elsevierStyleHsp" style=""></span>d vs&#46; placebo&#41;Durante 16 semanas&#42;Grupos con dupilumab&#58; dosis de carga de 600<span class="elsevierStyleHsp" style=""></span>mg el d&#237;a 1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Dupilumab 300<span class="elsevierStyleHsp" style=""></span>mg&#47;7<span class="elsevierStyleHsp" style=""></span>d vs&#46; 300<span class="elsevierStyleHsp" style=""></span>mg&#47;15<span class="elsevierStyleHsp" style=""></span>d vs&#46; placeboObjetivo primario&#58; IGA 0-1SOLO-1&#58; 37 vs&#46; 38 vs&#46; 10&#37;SOLO-2&#58; 36 vs&#46; 36 vs&#46; 8&#37;Mejor&#237;a significativa del EASI-75&#44; BSA&#44; SCORAD&#44; GISS&#44; prurito y calidad de vida&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Reacciones en el lugar de inyecci&#243;nConjuntivitis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleUnderline">NCT02277743</span>&#40;SOLO-1&#41;<span class="elsevierStyleUnderline">NCT02277769</span>&#40;SOLO-2&#41;NCT02612454NCT03054428&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Tralokinumab&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">IL-13 &#40;IL-13R&#945;1 e IL-13R&#945;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">SC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Moderada a grave&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">IIbIII&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Completado&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Aleatorizaci&#243;n 1&#58;1&#58;1&#58;1 &#40;tralokinumab 45&#44; 150 y 300<span class="elsevierStyleHsp" style=""></span>mg&#47;15<span class="elsevierStyleHsp" style=""></span>d vs&#46; placebo&#41;Uso concomitante de corticoides t&#243;picos&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Tralokinumab 300<span class="elsevierStyleHsp" style=""></span>mg&#58; reducci&#243;n del EASI &#40;diferencia media ajustada&#44; &#8722;4&#44;94&#59; IC 95&#37; &#8722;8&#44;76 a &#8722;1&#44;13&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;01&#41;&#46; IGA 0-1&#58; 26&#44;7 vs&#46; 11&#44;8&#37; para placebo&#46; Mejor&#237;a significativa del SCORAD&#44; DLQI y prurito&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Reacciones en el lugar de inyecci&#243;n&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleUnderline">NCT02347176</span>NCT03131648NCT03160885NCT03363854NCT03526861&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Lebrikizumab&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">IL-13&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">SC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Moderada a grave&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">II&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Completado&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Aleatorizaci&#243;n 1&#58;1&#58;1&#58;1 &#40;lebrikizumab 125<span class="elsevierStyleHsp" style=""></span>mg &#40;DU&#41; vs&#46; 250<span class="elsevierStyleHsp" style=""></span>mg &#40;DU&#41; vs&#46; 125<span class="elsevierStyleHsp" style=""></span>mg&#47;4<span class="elsevierStyleHsp" style=""></span>s vs&#46; placebo&#41;Uso concomitante de corticoides t&#243;picos&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Objetivo primarioEASI-50&#58; lebrikizumab 125<span class="elsevierStyleHsp" style=""></span>mg&#47;4<span class="elsevierStyleHsp" style=""></span>s &#40;82&#44;4&#37;&#41; vs&#46; placebo &#40;62&#44;3&#37;&#41;&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;026&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Reacciones en el lugar de inyecci&#243;nInfecciones herp&#233;ticas leves&#44; eosinofilia perif&#233;rica&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleUnderline">NCT02340234</span>NCT03443024&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="10" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="10" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Antagonismo de la polarizaci&#243;n Th2&#58; TSLP&#44; OX40L e IL-33</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Tezepelumab&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">TSLP&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">SC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Moderada a grave&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">IIaIIb&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Completado&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Aleatorizaci&#243;n 1&#58;1 &#40;tezepelumab 280<span class="elsevierStyleHsp" style=""></span>mg&#47;2<span class="elsevierStyleHsp" style=""></span>s vs&#46; placebo&#41;Uso concomitante de corticoides t&#243;picos&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">EASI-50 &#40;tezepelumab 64&#44;7&#37; vs&#46; placebo 48&#44;2&#37;&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;091&#41;No diferencias estad&#237;sticamente significativas&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Reacciones en el lugar de inyecci&#243;n&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleUnderline">NCT02525094</span>NCT03809663&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>MK-8226&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">TSLP-R&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">IV&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Moderada a grave&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">I&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Suspendido&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleUnderline">NCT01732510</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">GBR 830&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">OX40&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">IVSC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Moderada a grave&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">IIaIIb&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Completado&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Aleatorizaci&#243;n 3&#58;1GBR 830 10<span class="elsevierStyleHsp" style=""></span>mg&#47;kg vs&#46; placebo d&#237;as 1 y 29&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Porcentaje de pacientes que alcanzan EASI-50 con GBR 830 superior a placebo&#44; pero no diferencias estad&#237;sticamente significativas &#40;44 vs&#46; 20&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Buena tolerancia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleUnderline">NCT02683928</span>NCT03568162&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>KHK4083&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">OX40&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">IV&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Moderada a grave&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">III&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Completado&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">KHK-4083 0&#44;003 y 0&#44;001<span class="elsevierStyleHsp" style=""></span>mg&#47;kg y dosis ascendentes hasta 10<span class="elsevierStyleHsp" style=""></span>mg&#47;kg&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Tolerancia&#44; seguridad&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Buena tolerancia&#46; Se ha descrito el desarrollo de anticuerpos anti-KHK4083&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleUnderline">NCT03096223</span>NCT03703102&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Etokinab &#40;ANB020&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">IL-33&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">SC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Moderada a grave&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">II&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Activo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Etokinab vs&#46; placebo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleUnderline">NCT03533751</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="10" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="10" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Antagonismo de la respuesta TH22</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Fezakinumab&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">IL-22&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">IV&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Moderada a grave&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">II&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Completado&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Aleatorizaci&#243;n 2&#58;1Fezakinumab 600<span class="elsevierStyleHsp" style=""></span>mg &#40;d&#237;a 0&#41;&#44; seguido de 300<span class="elsevierStyleHsp" style=""></span>mg&#47;2<span class="elsevierStyleHsp" style=""></span>s &#40;&#250;ltima administraci&#243;n la semana 10&#41; vs&#46; placebo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Reducci&#243;n del SCORAD solo en el subgrupo de DA grave a las 12 semanas &#40;36&#44;4 vs&#46; 22&#44;3&#37;&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;05&#41; y a las 20 semanas &#40;46&#44;2 vs&#46; 22&#44;6&#37;&#59; p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;01&#41;&#46; No significaci&#243;n estad&#237;stica en el total &#40;incluyendo DA moderada&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Nasofaringitis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleUnderline">NCT01941537</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="10" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="10" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Antagonismo de la respuesta TH17 e IL-23</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Secukinumab&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">IL-17A&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">SC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Moderada a grave&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">II&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Completado&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Estudio paralelo con secukinumab &#40;misma posolog&#237;a que en psoriasis&#41; vs&#46; placebo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Evaluaci&#243;n a las 16 semanas&#46; Pendiente de publicaci&#243;n de resultados&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Buena tolerancia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleUnderline">NCT02594098</span>NCT03568136&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">MOR106&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">IL-17C&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">IV&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Moderada a grave&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">II&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Activo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">MOR106 a distintas dosis vs&#46; placebo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleUnderline">NCT03568071</span>NCT03689829NCT03864627&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Ustekinumab&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">IL-12&#44; IL-23 &#40;p40&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">SC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Moderada a grave&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">II&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Completado&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Estudio cruzado con ustekinumab &#40;misma posolog&#237;a que en psoriasis&#41; vs&#46; placebo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Mayor porcentaje de pacientes lograron una respuesta SCORAD-50 vs&#46; placebo&#44; pero no estad&#237;sticamente significativa&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Buena tolerancia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleUnderline">NCT01806662</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="10" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="10" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Bloqueo de la v&#237;a IL-31 y OSMR&#946;</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Nemolizumab&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">IL-31RA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">SC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Moderada a grave&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">II&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Completado&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Aleatorizaci&#243;n 1&#58;1&#58;1&#58;1Nemolizumab &#40;0&#44;1&#44; 0&#44;5 o 2<span class="elsevierStyleHsp" style=""></span>mg&#47;kg&#44; placebo&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Reducciones significativas del prurito dependientes de dosis para nemolizumab &#40;&#8722;63&#44;1&#37; para dosis de 0&#44;5<span class="elsevierStyleHsp" style=""></span>mg&#47;kg vs&#46; &#8722;20&#44;9&#37;&#41;&#46; Mejor&#237;a del EASI y SCORAD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Reacciones en el lugar de inyecci&#243;n&#44; nasofaringitis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleUnderline">NCT01986933</span>NCT03100344&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>BMS-981164&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">IL-31&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">SC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Moderada a grave&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">I&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Suspendido&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Sin resultados&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleUnderline">NCT01614756</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">KPL-716&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">OSMR&#946;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">IV&#47;SC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Moderada a grave&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Ia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Completado&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Dosis de 0&#44;3&#44; 1&#44;5 y 7&#44;5<span class="elsevierStyleHsp" style=""></span>mg&#47;kg vs&#46; placebo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Mejores resultados en reducci&#243;n del EASI y del prurito para las dosis de 7&#44;5<span class="elsevierStyleHsp" style=""></span>mg&#47;kg vs&#46; placebo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Buena toleranciaCefalea&#44; hiporexia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Mikhak et al&#46;<a class="elsevierStyleCrossRef" href="#bib0530"><span class="elsevierStyleSup">44</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="10" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="10" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Antagonismo de la IgE o de IL-5</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Omalizumab &#40;aprobado en asma&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">IgE&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">IV&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Moderada a graveGrave&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">IIIV&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CompletadoActivo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">OmalizumabOmalizumab vs&#46; placebo en pacientes de 4-19 a&#241;os con IgE<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>300<span class="elsevierStyleHsp" style=""></span>KU&#47;l&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Resultados no publicados-&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Resultados no publicados-&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleUnderline">NCT01179529</span><span class="elsevierStyleUnderline">NCT02300701</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Ligelizumab &#40;QGE031&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">IgE &#40;mayor afinidad que omalizumab&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">SC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Moderada a grave&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">II&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Completado&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Aleatorizaci&#243;n 1&#58;1&#58;1 &#40;ligelizumab&#47;2<span class="elsevierStyleHsp" style=""></span>s vs&#46; placebo vs&#46; CsA&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Resultados no publicados&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Resultados no publicados&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleUnderline">NCT01552629</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Mepolizumab &#40;aprobado en asma&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">IL-5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">SC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Moderada a grave&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">II&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Suspendido &#40;futilidad&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Mepolizumab 100<span class="elsevierStyleHsp" style=""></span>mg&#47;4<span class="elsevierStyleHsp" style=""></span>s vs&#46; placebo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Finalizaci&#243;n prematura del ensayo tras an&#225;lisis estad&#237;stico intermedio&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">No se ha demostrado eficacia&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleUnderline">NCT03055195</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="10" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="10" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleBold">F&#225;rmacos mol&#233;cula peque&#241;a</span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="10" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Inhibici&#243;n de la v&#237;a de se&#241;alizaci&#243;n JAK-STAT</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Baricitinib&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">JAK1&#44; JAK2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">VO&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Moderada a grave&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">IIIII&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CompletadoActivo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Aleatorizaci&#243;n 1&#58;1&#58;1 &#40;baricitinib 2<span class="elsevierStyleHsp" style=""></span>mg&#44; 4<span class="elsevierStyleHsp" style=""></span>mg&#44; placebo&#41; 1<span class="elsevierStyleHsp" style=""></span>v&#47;dJunto a aplicaci&#243;n t&#243;pica de corticoides&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">EASI-50&#58; mayor proporci&#243;n de pacientes para baricitinib 4<span class="elsevierStyleHsp" style=""></span>mg&#47;d vs&#46; placebo &#40;61 vs&#46; 37&#37;&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;027&#41; a las 16 semanas&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Buena tolerancia &#40;no casos de neoplasia&#44;eventos tromb&#243;ticos ni cardiovasculares&#41;&#44; ni herpes z&#243;ster&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleUnderline">NCT02576938</span>NCT03334396NCT03334422NCT03334435NCT03428100NCT03435081NCT03559270NCT03733301NCT03952559&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Upadacitinib &#40;ABT-494&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">JAK1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">VO&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Moderada a grave&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">IIbIII&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CompletadoActivo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Aleatorizaci&#243;n 1&#58;1&#58;1&#58;1 &#40;upadacitinib 7&#44;5&#44; 15 y 30<span class="elsevierStyleHsp" style=""></span>mg vs&#46; placebo&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Reducci&#243;n media del EASI a las 16 semanas a dosis de 30&#47;15&#47;7&#44;5<span class="elsevierStyleHsp" style=""></span>mg fue del 74&#47;62&#47;39&#37; vs&#46; placebo &#40;23&#37;&#41;&#59; p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;05&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Buena tolerancia&#46; Infecciones respiratorias de v&#237;as altas y acn&#233;&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleUnderline">NCT02925117</span>NCT03607422NCT03568318NCT03738397NCT03661138&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Abrocitinib &#40;PF-04965842&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">JAK1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">VO&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Moderada a grave&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">IIbIII&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CompletadoActivo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Aleatorizaci&#243;n 1&#58;1&#58;1&#58;1&#58;1 &#40;abrocitinib 10&#44; 30&#44; 100 y 200<span class="elsevierStyleHsp" style=""></span>mg&#44; placebo&#41; 1<span class="elsevierStyleHsp" style=""></span>v&#47;d&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Porcentaje IGA 0-1 y mejor&#237;a de<span class="elsevierStyleHsp" style=""></span>&#8805;<span class="elsevierStyleHsp" style=""></span>2 puntos respecto el basal&#44; significativamente mayor para abrocitinib 200<span class="elsevierStyleHsp" style=""></span>mg&#47;d vs&#46; placebo &#40;44&#44;5 vs&#46; 6&#44;3&#37;&#41; a las 12 semanas&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Buena tolerancia&#44; un caso de eccema herpeticum y uno de neumon&#237;a&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleUnderline">NCT02780167</span>NCT03349060NCT03422822NCT03575871NCT03627767NCT03720470&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ASN002&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">PAN-JAK &#40;JAK1&#44; JAK2&#44; JAK3&#44; TYK&#41;&#44; SYK&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">VO&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Moderada a grave&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">III&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Completado&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Aleatorizaci&#243;n 1&#58;1&#58;1&#58;1 &#40;ASN002 20&#44; 40 y 80<span class="elsevierStyleHsp" style=""></span>mg vs&#46; placebo&#41;Durante 28 d&#237;as&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Proporci&#243;n de pacientes que alcanzan EASI-75 significativamente superior para ASN002 40<span class="elsevierStyleHsp" style=""></span>mg &#40;71&#44;4&#37;&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;06&#41; y para ASN002 80<span class="elsevierStyleHsp" style=""></span>mg &#40;33&#44;3&#37;&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;65&#41; vs&#46; placebo &#40;22&#44;2&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Buena tolerancia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleUnderline">NCT03139981</span>NCT03531957&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="10" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="10" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Antagonismo de la PDE4</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Apremilast&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">PDE4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">VO&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Moderada a grave&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">II&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Completado&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Dise&#241;o paralelo 1&#58;1&#58;1&#58;1 &#40;apremilast 30<span class="elsevierStyleHsp" style=""></span>mg&#47;12<span class="elsevierStyleHsp" style=""></span>h&#44; 40<span class="elsevierStyleHsp" style=""></span>mg&#47;12<span class="elsevierStyleHsp" style=""></span>h vs&#46; placebo&#47;apremilast 30<span class="elsevierStyleHsp" style=""></span>mg&#47;12<span class="elsevierStyleHsp" style=""></span>h vs&#46; placebo&#47;apremilast 40<span class="elsevierStyleHsp" style=""></span>mg&#47;12<span class="elsevierStyleHsp" style=""></span>h&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Reducci&#243;n significativa del EASI respecto al basal a las 12 semanas de apremilast 40<span class="elsevierStyleHsp" style=""></span>mg&#47;12<span class="elsevierStyleHsp" style=""></span>h vs&#46; placebo &#40;31&#44;57 vs&#46; 10&#44;98&#37;&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;034&#41;&#46; No ventajas respecto a EASI-50 ni prurito&#46; No diferencias significativas a 30<span class="elsevierStyleHsp" style=""></span>mg&#47;12<span class="elsevierStyleHsp" style=""></span>h&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Diarrea&#44; n&#225;useas&#44; molestias abdominales&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleUnderline">NCT02087943</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="10" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="10" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Antagonismo del H4R</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">JNJ-39758979&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">H4R&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">VO&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Moderada&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">II&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Suspendido &#40;efectos adversos&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">JNJ-39758979 300 o 100<span class="elsevierStyleHsp" style=""></span>mg vs&#46; placebo 1<span class="elsevierStyleHsp" style=""></span>v&#47;d&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Terminaci&#243;n temprana del ensayo cl&#237;nico&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Dos casos de neutropenia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleUnderline">NCT01497119</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ZPL389&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">H4R&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">VO&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Moderada a grave&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">II&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Completado&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ZPL-389 30<span class="elsevierStyleHsp" style=""></span>mg vs&#46; placebo 1<span class="elsevierStyleHsp" style=""></span>v&#47;d&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Mejor&#237;a significativa del EASI &#40;50 vs&#46; 27&#37;&#41;&#46; No diferencias significativas en cuanto al prurito&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Buena tolerancia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleUnderline">NCT02424253</span>NCT03517566&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="10" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="10" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Bloqueo del NKR1</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Serlopitant&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NKR1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">VO&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Leve&#44; moderada o grave&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">II&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Completado&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Aleatorizaci&#243;n 1&#58;1&#58;1 &#40;serlopitant 1 y 5<span class="elsevierStyleHsp" style=""></span>mg vs&#46; placebo&#41;6 semanas&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Reducci&#243;n del prurito no significativa frente a placebo &#40;&#8722;2&#44;25 vs&#46; &#8722;2&#44;32 vs&#46; &#8722;2&#44;01&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Buena tolerancia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleUnderline">NCT02975206</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Tradipitant&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NKR1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">VO&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Leve&#44; moderada o grave&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">IIIIIII&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CompletadoCompletadoActivo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Aleatorizaci&#243;n 1&#58;1 &#40;tradipitant 100<span class="elsevierStyleHsp" style=""></span>mg&#47;24<span class="elsevierStyleHsp" style=""></span>h vs&#46; placebo&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Reducci&#243;n del prurito no significativa frente a placeboSin otros resultados&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Buena tolerancia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleUnderline">NCT02004041</span>NCT02651714NCT03568331&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="10" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="10" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Agonismo del kOR</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Asimadolina&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Agonista del kOR&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">VO&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Leve&#44; moderada o grave&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">II&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Completado&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Aleatorizaci&#243;n 1&#58;1 &#40;amisadolina 2&#44;5<span class="elsevierStyleHsp" style=""></span>mg&#47;12<span class="elsevierStyleHsp" style=""></span>h vs&#46; placebo&#47;12<span class="elsevierStyleHsp" style=""></span>h&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Sin resultados&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Sin resultados&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NCT02475447&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="10" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="10" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Otras mol&#233;culas</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">DS107&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">DGLA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">VO&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Moderada a grave&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">II&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Completado&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Aleatorizaci&#243;n 1&#58;1&#58;1 &#40;DS107 1<span class="elsevierStyleHsp" style=""></span>g vs&#46; 2<span class="elsevierStyleHsp" style=""></span>g vs&#46; placebo&#41;1<span class="elsevierStyleHsp" style=""></span>v&#47;d&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Resultados no publicados&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Resultados no publicados&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NCT02864498&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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          "leyenda" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">ADSI&#58; <span class="elsevierStyleItalic">Atopic Dermatitis Severity Index&#59;</span> AhR&#58; <span class="elsevierStyleItalic">aryl hydrocarbon receptor&#59;</span> BSA&#58; Body Surface Area&#59; CRTH2&#58; receptor transmembrana de la prostaglandina 2&#59; CsA&#58; ciclosporina A&#59; EASI&#58; <span class="elsevierStyleItalic">Eczema Area and Severity Index&#59;</span> EVA&#58; escala visual anal&#243;gica&#59; IGA&#58; <span class="elsevierStyleItalic">Investigator Global Assessment&#59;</span> LXR&#58; <span class="elsevierStyleItalic">liver X receptors&#59;</span> JAK&#58; Janus kinase&#59; PAM&#58; p&#233;ptido antimicrobiano&#59; PDE4&#58; fosfodiesterasa 4&#59; PGA&#58; physician global assessment&#59; SCORAD&#58; <span class="elsevierStyleItalic">SCORing Atopic Dermatitis&#59;</span> SYK&#58; <span class="elsevierStyleItalic">spleen tyrosine kinase&#59;</span> TEWL&#58; <span class="elsevierStyleItalic">transepidermal water loss&#59;</span> TrkA&#58; <span class="elsevierStyleItalic">tyrosine receptor kinase-A&#46;</span></p><p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">Los datos mencionados espec&#237;ficamente en la tabla pertenecen a los ensayos cl&#237;nicos &#40;ID&#41; se&#241;alados mediante subrayado&#46;</p>"
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                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">F&#225;rmaco&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Diana&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Gravedad&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Fase&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Estado&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Intervenci&#243;n&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Eficacia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Seguridad&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Ensayos cl&#237;nicos &#40;ID&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="9" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Inhibidores t&#243;picos de la se&#241;alizaci&#243;n JAK&#47;STAT</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Tofacitinib&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">PAN-JAK &#40;m&#225;s selectivo JAK1 y JAK3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Leve a moderada&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">II&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Completado&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Aleatorizaci&#243;n 1&#58;1Tofacitinib 2&#37; t&#243;pico vs&#46; placebo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Mejor&#237;a del EASI respecto al basal significativamente superior al veh&#237;culo &#40;&#8722;81&#44;7 vs&#46; &#8722;29&#44;9&#37;&#59; p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#41;&#46; Mejor&#237;as significativas del PGA&#44; BSA y del prurito&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Buena tolerancia&#46; Dolor&#47;quemaz&#243;n en el lugar de aplicaci&#243;n&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleUnderline">NCT02001181</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Ruxolitinib&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">JAK1&#44; JAK2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Leve a moderada&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">II&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Completado&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Ruxolitinib a distintas concentraciones vs&#46; triamcinolona 0&#44;1&#37; vs&#46; placebo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Mejor&#237;a del EASI respecto al basal significativamente superior al placebo para las dosis de 1&#44;5&#37; &#63;una o 2 veces al d&#237;a&#63; y 0&#44;5&#37; &#63;una vez al d&#237;a&#63; a las 4 semanas &#40;71&#44;6&#47;67&#47;52&#44;2&#37; vs&#46; 15&#44;5&#37;&#59; p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Buena tolerancia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleUnderline">NCT03011892</span>NCT03257644NCT03745651NCT03920852&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Cerdulatinib &#40;RVT-502&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">PAN-JAK&#44; SYK&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">I&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Delgocitinib &#40;JTE-052&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">PAN-JAK&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Moderada a grave&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">II&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Completado&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Aleatorizaci&#243;n 2&#58;2&#58;2&#58;2&#58;1&#58;1 &#40;delgocitinib 0&#44;25&#37;&#44; 0&#44;5&#37;&#44; 1&#37;&#44; 3&#37;&#44; veh&#237;culo&#44; tacrolimus 0&#44;1&#37;&#41; 2<span class="elsevierStyleHsp" style=""></span>v&#47;d&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Mejor&#237;a del EASI respecto al basal para todas las dosis de delgocitinib &#40;0&#44;25&#44; 0&#44;5&#44; 1 y 3&#37;&#41; significativamente superior al veh&#237;culo &#40;&#8722;41&#44;7&#44; &#8722;57&#44;1&#44; &#8722;54&#44;9&#44; &#8722;72&#44;9 vs&#46; 12&#44;2&#37;&#44; respectivamente&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#41;&#46; Reducci&#243;n del prurito&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Buena tolerancia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleUnderline">JapicCTI-152887</span>NCT03725722NCT03826901NCT03683719&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>SNA-125&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">JAK3&#44; TrkA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">I&#47;II&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="9" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="9" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Inhibidores de la PDE4</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Crisaborol&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">PDE4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Leve a moderada&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">III&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Completado&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2 ensayos de intervenci&#243;n id&#233;ntica&#44; pacientes<span class="elsevierStyleHsp" style=""></span>&#8805;<span class="elsevierStyleHsp" style=""></span>2 a&#241;osAleatorizaci&#243;n 2&#58;1 &#40;crisaborol&#58;veh&#237;culo&#41;Aplicaci&#243;n 2 veces al d&#237;a&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Evaluaci&#243;n a las 4 semanas del IGA 0&#47;1&#44; con mejor&#237;as significativas frente al veh&#237;culo&#58; 51&#44;7 vs&#46; 40&#44;6&#37;&#44; p&#160;&#61;&#160;0&#44;005&#59; 48&#44;5 vs&#46; 29&#44;7&#37;&#44; p&#160;&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;0019&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Dolor&#47;quemaz&#243;n en el lugar de aplicaci&#243;n&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleUnderline">NCT02118766</span><span class="elsevierStyleUnderline">NCT02118792</span>NCT01301508NCT01602341NCT01652885NCT03233529NCT03260595NCT03250663&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>E6005&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">PDE4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Leve a moderada&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">II&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Completado&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Aleatorizaci&#243;n 1&#58;1 &#40;E6005 0&#44;2&#37; vs&#46; veh&#237;culo&#41;Aplicaci&#243;n 2 veces al d&#237;a&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Evaluaci&#243;n a la semana 12&#58; reducci&#243;n significativa del EASI respecto al basal &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;030&#41; y SCORAD &#40;&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Buena tolerancia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleUnderline">NCT01461941</span>NCT01179880NCT02094235&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>AN2898&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">PDE4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Leve a moderada&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">II&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Completado&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Comparaci&#243;n con placebo de AN2898 al 2&#37; en una lesi&#243;n activa vs&#46; placebo en otra lesi&#243;n activaAplicaci&#243;n 2 veces al d&#237;a&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Mejor&#237;a significativa del ADSI respecto al basal&#44; mayor proporci&#243;n de lesiones con aclaramiento total o parcial ADSI<span class="elsevierStyleHsp" style=""></span>&#8804;<span class="elsevierStyleHsp" style=""></span>2&#59; 48 vs&#46; 33&#37;&#41; en comparaci&#243;n con el veh&#237;culo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Buena tolerancia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleUnderline">NCT01301508</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>MM36 &#40;OPA-15406&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">PDE4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Leve a moderada&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">IIIII&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CompletadoActivo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Aleatorizaci&#243;n 1&#58;1&#58;1MM36 0&#44;3&#37; vs&#46; 1&#37; vs&#46; veh&#237;culoAplicaci&#243;n 2 veces al d&#237;a&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Reducci&#243;n de IGA de 0&#47;1 o reducci&#243;n en 2 puntos&#58; MM36 al 1&#37;&#58; 20&#44;9 vs&#46; 2&#44;7&#37; para el veh&#237;culo&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;0165&#41; a la semana 4&#46; Reducci&#243;n de EASI&#58; OPA-15406 al 1&#37;&#58; 39 vs&#46; 3&#37; para el veh&#237;culo&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;005&#41; a la semana 2Reducci&#243;n del prurito&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Buena tolerancia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleUnderline">NCT02068352</span>NCT02945657NCT02914548NCT03018691NCT01702181NCT02334787NCT03961529&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Roflumilast&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">PDE4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Moderada&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">IIa&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Completado&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Aleatorizaci&#243;n 1&#58;1Roflumilast 0&#44;5&#37; vs&#46; veh&#237;culoAplicaci&#243;n 2 veces al d&#237;a&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">No se observaron diferencias en SCORAD&#44; prurito &#40;EVA 100<span class="elsevierStyleHsp" style=""></span>mm&#41; ni TEWL a la semana 2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Buena tolerancia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleUnderline">NCT01856764</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="9" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="9" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Otras dianas</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Omiganan&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Es un PAM&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Leve a moderada&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">II&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Completado&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Aleatorizaci&#243;n 1&#58;1&#58;1&#58;1 &#40;omiganan 1&#37;&#44; 1&#44;75&#37;&#44; 2&#44;5&#37;&#44; veh&#237;culo&#41;Aplicaci&#243;n 2 veces al d&#237;a&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Evaluaci&#243;n a las 7 semanas del SCORAD&#44; EASI e IGAResultados no publicados&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Resultados no publicados&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">NCT03091426NCT02456480&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Tapinarof &#40;GSK2894512&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Agonista del AhR&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Moderada a grave&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">II&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Completado&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Aleatorizaci&#243;n 1&#58;1&#58;1&#58;1&#58;1&#58;1 &#40;tapinarof 1&#37; 2<span class="elsevierStyleHsp" style=""></span>v&#47;d&#44; 1&#37; 1<span class="elsevierStyleHsp" style=""></span>v&#47;d&#44; 0&#44;5&#37; 2<span class="elsevierStyleHsp" style=""></span>v&#47;d&#44; 0&#44;5&#37; 1<span class="elsevierStyleHsp" style=""></span>v&#47;d&#44; veh&#237;culo 2<span class="elsevierStyleHsp" style=""></span>v&#47;d&#44; veh&#237;culo 1<span class="elsevierStyleHsp" style=""></span>v&#47;d&#41;&#42;Pacientes de 12-65 a&#241;os&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Proporci&#243;n de pacientes con IGA de 0 o 1&#58; 53&#37; &#40;tapinarof 1&#37; 2<span class="elsevierStyleHsp" style=""></span>v&#47;d&#41; vs&#46; 24&#37; &#40;veh&#237;culo 2<span class="elsevierStyleHsp" style=""></span>v&#47;d&#41; a las 12 semanas&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Buena toleranciaDermatitis de contacto &#40;infrecuente&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleUnderline">NCT02564055</span>NCT01098734NCT00837551&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>PR022&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#193;cido hipocloroso&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Leve a moderada&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">II&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Activo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Aleatorizaci&#243;n 1&#58;1&#58;1 &#40;PR022 al 0&#44;05&#37;&#44; 0&#44;1&#37;&#44; veh&#237;culo&#41;Durante 28 d&#237;as&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Sin resultados&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Sin resultados&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleUnderline">NCT03351777</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>SP14019&#47;Cyclatop&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CsA t&#243;pica&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Leve a moderada&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">II&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Completado&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Aleatorizaci&#243;n 1&#58;1Soluci&#243;n de ciclosporina al 5&#37; vs&#46; veh&#237;culoDurante 4 semanasPacientes<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>2 a&#241;os&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Mejor&#237;as significativas de Cyclatop frente a veh&#237;culo en EASI &#40;51&#44;2 vs&#46; 23&#44;6&#37;&#41;&#44; ADSI &#40;55&#44;4 vs&#46; 34&#37;&#41; e IGA &#40;61&#44;5&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Buena tolerancia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleUnderline">NCT02865356</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Q301&#47;Zyleuton&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Antagonista del CRTH2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Moderada a grave&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">II&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Completado&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Aleatorizaci&#243;n 1&#58;1Q301 en crema &#40;dosis no conocidas&#41; al vs&#46; placebo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Resultados no publicados&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Resultados no publicados&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleUnderline">NCT02426359</span>NCT03571620&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>VTP-38543&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Agonista del LXR&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Leve a moderada&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">I&#47;II&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Completado&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Aleatorizaci&#243;n 1&#58;1&#58;1&#58;1&#58;1 &#40;VTP-38543 0&#44;05&#37;&#47;12<span class="elsevierStyleHsp" style=""></span>h&#44; 0&#44;15&#37;&#47;12<span class="elsevierStyleHsp" style=""></span>h vs&#46; veh&#237;culo sin Transcutol&#174;&#47;12<span class="elsevierStyleHsp" style=""></span>h&#44; vs&#46; VTP-38543 1&#37;&#47;12<span class="elsevierStyleHsp" style=""></span>h vs&#46; veh&#237;culo sin Transcutol&#174;&#47;12<span class="elsevierStyleHsp" style=""></span>h&#41;Durante 28 d&#237;as&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">No reducci&#243;n significativa del EASI ni del SCORAD frente al veh&#237;culo&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Buena tolerancia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleUnderline">NCT02655679</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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          "es" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Resumen de los tratamientos t&#243;picos de nuevo desarrollo y en fases de investigaci&#243;n para dermatitis at&#243;pica</p>"
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    "bibliografia" => array:2 [
      "titulo" => "Bibliograf&#237;a"
      "seccion" => array:1 [
        0 => array:2 [
          "identificador" => "bibs0015"
          "bibliografiaReferencia" => array:62 [
            0 => array:3 [
              "identificador" => "bib0315"
              "etiqueta" => "1"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Public health burden and epidemiology of atopic dermatitis"
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                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "J&#46;I&#46; Silverberg"
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                    0 => array:2 [
                      "doi" => "10.1016/j.det.2017.02.002"
                      "Revista" => array:6 [
                        "tituloSerie" => "Dermatol Clin&#46;"
                        "fecha" => "2017"
                        "volumen" => "35"
                        "paginaInicial" => "283"
                        "paginaFinal" => "289"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/28577797"
                            "web" => "Medline"
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            1 => array:3 [
              "identificador" => "bib0320"
              "etiqueta" => "2"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Guidelines for treatment of atopic eczema &#40;atopic dermatitis&#41; part <span class="elsevierStyleSmallCaps">i</span>"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "J&#46; Ring"
                            1 => "A&#46; Alomar"
                            2 => "T&#46; Bieber"
                            3 => "M&#46; Deleuran"
                            4 => "A&#46; Fink-Wagner"
                            5 => "C&#46; Gelmetti"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1111/j.1468-3083.2012.04635.x"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Eur Acad Dermatol Venereol&#46;"
                        "fecha" => "2012"
                        "volumen" => "26"
                        "paginaInicial" => "1045"
                        "paginaFinal" => "1060"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22805051"
                            "web" => "Medline"
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Article information
ISSN: 00017310
Original language: Spanish
DOI:10.1016/j.ad.2019.11.002
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