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1</a>A&#41;&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0015" class="elsevierStylePara elsevierViewall">Dado que la respuesta inmune est&#225; coordinada y regulada por mediadores solubles que en su mayor&#237;a son citocinas proinflamatorias&#44; la v&#237;a JAK&#47;STAT es una diana terap&#233;utica en diferentes enfermedades inflamatorias inmunomediadas&#46; Los inhibidores de JAK &#40;JAKi&#41; son mol&#233;culas peque&#241;as que inhiben la actividad cinasa de las JAK y disminuyen de forma efectiva la transducci&#243;n intracelular de la v&#237;a JAK&#47;STAT &#40;<a class="elsevierStyleCrossRef" href="#fig0005">fig&#46; 1</a>B&#41;&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">En los &#250;ltimos a&#241;os&#44; m&#250;ltiples JAKi han demostrado su eficacia en enfermedades como la artritis reumatoide&#44; la mielofibrosis o la policitemia vera&#46; Los JAKi de primera generaci&#243;n &#8211;como ruxolitinib&#44; 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2</a>&#41;&#46; Al disminuir el efecto de todas las citocinas que activan la v&#237;a JAK&#47;STAT correspondiente podr&#237;an ser m&#225;s eficaces que los biol&#243;gicos cl&#225;sicos que solo van dirigidos a una citocina<a class="elsevierStyleCrossRef" href="#bib0515"><span class="elsevierStyleSup">3</span></a>&#46; Otra de las ventajas de los JAKi es su peque&#241;o tama&#241;o&#44; lo que hace que las mol&#233;culas penetren f&#225;cilmente la barrera epid&#233;rmica y se puedan usar en formulaciones t&#243;picas<a class="elsevierStyleCrossRef" href="#bib0520"><span class="elsevierStyleSup">4</span></a>&#46;</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><p id="par0030" class="elsevierStylePara elsevierViewall">Los JAKi tienen un perfil de riesgo-beneficio aceptable&#44; aunque los resultados en su mayor&#237;a proceden de estudios realizados en enfermedades inflamatorias como la artritis reumatoide&#46; La mayor&#237;a de los efectos adversos descritos son leves a moderados<a class="elsevierStyleCrossRefs" href="#bib0525"><span class="elsevierStyleSup">5&#8211;10</span></a>&#59; los m&#225;s frecuentes son las infecciones de v&#237;as respiratorias altas&#44; urinarias y gastrointestinales&#46; En pacientes tratados con baricitinib se ha observado un aumento en el riesgo de reactivaci&#243;n del virus herpes z&#243;ster<a class="elsevierStyleCrossRef" href="#bib0555"><span class="elsevierStyleSup">11</span></a>&#44; que duplica el riesgo de los biol&#243;gicos inhibidores del factor de necrosis tumoral<a class="elsevierStyleCrossRefs" href="#bib0560"><span class="elsevierStyleSup">12&#44;13</span></a>&#46; Tofacitinib se ha asociado con el desarrollo de herpes z&#243;ster en el 1-3&#37; de los casos<a class="elsevierStyleCrossRefs" href="#bib0570"><span class="elsevierStyleSup">14&#8211;16</span></a>&#46; Adem&#225;s se han descrito casos de reactivaci&#243;n de tuberculosis con tofacitinib y baricitinib<a class="elsevierStyleCrossRefs" href="#bib0525"><span class="elsevierStyleSup">5&#44;12&#44;14&#8211;16</span></a>&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">Los resultados de un ensayo en artritis reumatoide comparando tofacitinib 5<span class="elsevierStyleHsp" style=""></span>mg o 10<span class="elsevierStyleHsp" style=""></span>mg 2 veces al d&#237;a con etanercept &#8211;un inhibidor del factor de necrosis tumoral&#8211; identificaron un riesgo aumentado de trombosis en el grupo de 10<span class="elsevierStyleHsp" style=""></span>mg 2 veces al d&#237;a con respecto al grupo placebo&#44; aunque se precisan estudios adicionales para confirmar este hallazgo<a class="elsevierStyleCrossRef" href="#bib0585"><span class="elsevierStyleSup">17</span></a>&#46; Diversos metaan&#225;lisis y revisiones sistem&#225;ticas no han encontrado un incremento en la incidencia de neoplasias para tofacitinib<a class="elsevierStyleCrossRefs" href="#bib0590"><span class="elsevierStyleSup">18&#8211;20</span></a>&#46; Otros estudios describen una incidencia de neoplasias similar a la de los biol&#243;gicos<a class="elsevierStyleCrossRefs" href="#bib0595"><span class="elsevierStyleSup">19&#44;21</span></a>&#46; Sin embargo&#44; se han observado linfomas B agresivos en pacientes con neoplasias mieloproliferativas tratados con ruxolitinib<a class="elsevierStyleCrossRef" href="#bib0610"><span class="elsevierStyleSup">22</span></a>&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">La inhibici&#243;n de JAK2 interfiere con la eritropoyesis&#44; la mielopoyesis y la activaci&#243;n plaquetaria&#44; por lo que confiere riesgo de anemia&#44; neutropenia y trombocitopenia<a class="elsevierStyleCrossRefs" href="#bib0535"><span class="elsevierStyleSup">7&#44;8&#44;23&#8211;26</span></a>&#46; Ruxolitinib&#44; debido a su elevada potencia como inhibidor de JAK2&#44; produce m&#225;s mielosupresi&#243;n que otros inhibidores de JAK&#46; La inhibici&#243;n de JAK1 se ha asociado a un incremento en los niveles de colesterol total&#44; LDL&#44; HDL&#44; y triglic&#233;ridos<a class="elsevierStyleCrossRefs" href="#bib0540"><span class="elsevierStyleSup">8&#44;24&#44;27&#8211;30</span></a>&#44; aunque se normalizan al cabo de 1-3 meses&#46; Tambi&#233;n se puede observar incremento transitorio en los niveles de enzimas hep&#225;ticas&#44; CPK y creatinina&#44; reversibles tras la suspensi&#243;n del f&#225;rmaco<a class="elsevierStyleCrossRefs" href="#bib0620"><span class="elsevierStyleSup">24&#44;27&#44;28&#44;31</span></a>&#46; La p&#233;rdida de actividad de TYK2 puede incrementar el riesgo de infecciones cut&#225;neas severas por herpesvirus&#44; estafilococo y micobacterias<a class="elsevierStyleCrossRef" href="#bib0660"><span class="elsevierStyleSup">32</span></a>&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">El perfil de seguridad de los JAKi t&#243;picos es mejor que el de los orales&#44; como corresponde a su escasa absorci&#243;n sist&#233;mica<a class="elsevierStyleCrossRefs" href="#bib0545"><span class="elsevierStyleSup">9&#44;33&#8211;35</span></a>&#46; Se han empleado en crema&#44; en pomada y en base liposomal&#44; presentando irritaci&#243;n cut&#225;nea y foliculitis en funci&#243;n del veh&#237;culo utilizado&#46; En un estudio con ruxolitinib en crema&#44; se ha descrito la aparici&#243;n de eritema &#40;72&#37;&#41;&#44; hiperpigmentaci&#243;n y acn&#233; transitorio<a class="elsevierStyleCrossRef" href="#bib0665"><span class="elsevierStyleSup">33</span></a>&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Inhibidores de JAK en dermatolog&#237;a</span><p id="par0050" class="elsevierStylePara elsevierViewall">Se ha demostrado una disregulaci&#243;n de la v&#237;a de se&#241;alizaci&#243;n JAK&#47;STAT en distintas enfermedades inflamatorias dermatol&#243;gicas&#44; con diferencias de expresi&#243;n de JAK en biopsias de piel sana y enferma<a class="elsevierStyleCrossRef" href="#bib0680"><span class="elsevierStyleSup">36</span></a>&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">En psoriasis&#44; lupus eritematoso cut&#225;neo&#44; pioderma gangrenoso&#44; dermatitis at&#243;pica &#40;DA&#41; y alopecia areata &#40;AA&#41; se ha demostrado sobreexpresi&#243;n de mol&#233;culas JAK en la epidermis y&#47;o la dermis<a class="elsevierStyleCrossRef" href="#bib0680"><span class="elsevierStyleSup">36</span></a>&#46; La expresi&#243;n de JAK3 est&#225; muy aumentada en la epidermis de dichas enfermedades excepto en el lupus&#44; con posibles implicaciones terap&#233;uticas en cuanto al empleo de inhibidores t&#243;picos de JAK3&#46; Por ejemplo&#44; se ha empleado tofacitinib t&#243;pico para el tratamiento de la psoriasis&#44; la AA<a class="elsevierStyleCrossRefs" href="#bib0685"><span class="elsevierStyleSup">37&#8211;39</span></a> y la DA<a class="elsevierStyleCrossRef" href="#bib0545"><span class="elsevierStyleSup">9</span></a>&#44; mientras que se ha ensayado delgocitinib t&#243;pico para el tratamiento de la DA<a class="elsevierStyleCrossRefs" href="#bib0700"><span class="elsevierStyleSup">40&#44;41</span></a>&#46; En cambio&#44; en el lupus eritematoso cut&#225;neo se ha demostrado un aumento de actividad JAK1 en la dermis y los inhibidores selectivos de JAK1 podr&#237;an ser de utilidad para su tratamiento<a class="elsevierStyleCrossRef" href="#bib0710"><span class="elsevierStyleSup">42</span></a>&#46; JAK1&#44; JAK2&#44; JAK3 se encuentran sobreexpresados en la dermis de pioderma gangrenoso y DA&#44; lo que indica la posible utilidad terap&#233;utica de los inhibidores pan-JAK&#44; como por ejemplo tofacitinib&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall">A continuaci&#243;n&#44; se describe de forma detallada el papel de la v&#237;a JAK-STAT en vit&#237;ligo y AA y los resultados obtenidos con los JAKi en diferentes estudios&#46; Asimismo&#44; en la parte 2 de esta revisi&#243;n se profundizar&#225; en la patog&#233;nesis y el papel de los JAKi en psoriasis&#44; DA y otras dermatosis&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Vit&#237;ligo</span><p id="par0065" class="elsevierStylePara elsevierViewall">Se ha observado que en la piel humana con vit&#237;ligo hay niveles elevados de interfer&#243;n gamma &#40;IFN-&#947;&#41; y sus citocinas asociadas&#44; CXCL9 y CXCL10&#46; El IFN-&#947; activa&#44; a trav&#233;s de JAK1&#47;2<a class="elsevierStyleCrossRef" href="#bib0715"><span class="elsevierStyleSup">43</span></a>&#44; la transcripci&#243;n de CXCL9 y CXCL10&#44; necesarios para el reclutamiento de los linfocitos T citot&#243;xicos&#44; que son los efectores finales de la destrucci&#243;n melanoc&#237;tica &#40;<a class="elsevierStyleCrossRef" href="#fig0010">fig&#46; 2</a>&#41;&#46; Inhibir las JAK podr&#237;a ser una estrategia terap&#233;utica efectiva para el tratamiento del vit&#237;ligo&#44; reduciendo as&#237; la producci&#243;n de CXCL9 y CXCL10<a class="elsevierStyleCrossRefs" href="#bib0720"><span class="elsevierStyleSup">44&#44;45</span></a>&#46;</p><p id="par0070" class="elsevierStylePara elsevierViewall">En un reciente metaan&#225;lisis que incluy&#243; a 45 pacientes con vit&#237;ligo tratados con JAKi&#44; se observ&#243; repigmentaci&#243;n superior al 50&#37; en el 57&#44;8&#37; de los pacientes&#44; llegando al 70&#37; en el caso del vit&#237;ligo facial y al 88&#44;9&#37; cuando se usaba fototerapia concomitante<a class="elsevierStyleCrossRef" href="#bib0730"><span class="elsevierStyleSup">46</span></a>&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">Sin embargo&#44; se ha observado que al interrumpir el tratamiento con JAKi se producen reca&#237;das&#44; que podr&#237;an ser determinadas por la presencia de c&#233;lulas autorreactivas de memoria residentes en la piel &#40;Trm&#41;&#46; Se cree que la IL-15 &#8211;cuya expresi&#243;n se encuentra incrementada en la epidermis de vit&#237;ligo<a class="elsevierStyleCrossRef" href="#bib0735"><span class="elsevierStyleSup">47</span></a>&#8211; desempe&#241;a un papel fundamental en el mantenimiento de los Trm CD8&#43;&#44; lo que sugiere que podr&#237;a ser un tratamiento dirigido efectivo en los pacientes con vit&#237;ligo<a class="elsevierStyleCrossRef" href="#bib0740"><span class="elsevierStyleSup">48</span></a>&#46;</p><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Tofacitinib oral</span><p id="par0080" class="elsevierStylePara elsevierViewall">Tofacitinib &#40;Xeljanz&#174;&#44; Pfizer&#41; es un inhibidor JAK1&#47;3 cuya eficacia se ha observado en casos cl&#237;nicos o series de casos con vit&#237;ligo&#46; Con la dosis de 5<span class="elsevierStyleHsp" style=""></span>mg al d&#237;a se obtuvo repigmentaci&#243;n casi completa de cara y manos en una paciente con vit&#237;ligo progresivo a los 5 meses&#44; sin efectos adversos&#44; pero la mejor&#237;a no se mantuvo al suspender el tratamiento<a class="elsevierStyleCrossRef" href="#bib0745"><span class="elsevierStyleSup">49</span></a>&#46; En otra paciente con vit&#237;ligo no segmentario multifocal en la que se inici&#243; tofacitinib 5<span class="elsevierStyleHsp" style=""></span>mg 2 veces al d&#237;a durante 6 meses para el tratamiento de una DA concomitante&#44; se consigui&#243; una mejor&#237;a discreta del vit&#237;ligo &#40;reducci&#243;n del Vitiligo Area Scoring Index &#8211;VASI score&#8211; de 4&#44;68 basal a 3&#44;95 a los 5 meses&#41;&#46; Present&#243; 2 episodios de infecci&#243;n de v&#237;as respiratorias altas y uno de diarrea que no requirieron la interrupci&#243;n del tratamiento<a class="elsevierStyleCrossRef" href="#bib0750"><span class="elsevierStyleSup">50</span></a>&#46;</p><p id="par0085" class="elsevierStylePara elsevierViewall">La repigmentaci&#243;n de pacientes con vit&#237;ligo en tratamiento con JAKi podr&#237;a requerir fotoestimulaci&#243;n para inducir la migraci&#243;n de melanocitos a la epidermis&#46; En una serie retrospectiva de 10 pacientes&#44; el tratamiento con tofacitinib 5-10<span class="elsevierStyleHsp" style=""></span>mg una o 2 veces al d&#237;a&#44; &#250;nicamente llev&#243; a la repigmentaci&#243;n cuando se daba concomitantemente con la exposici&#243;n a luz solar o UVB banda estrecha &#40;nb-UVB&#41;<a class="elsevierStyleCrossRef" href="#bib0755"><span class="elsevierStyleSup">51</span></a>&#46; Otro estudio multic&#233;ntrico retrospectivo determin&#243; que los pacientes tratados con nb-UVB junto con tofacitinib 10<span class="elsevierStyleHsp" style=""></span>mg al d&#237;a presentaron mejores tasas de repigmentaci&#243;n en comparaci&#243;n con la fototerapia sola &#40;92 vs&#46; 77&#37;&#41;<a class="elsevierStyleCrossRef" href="#bib0760"><span class="elsevierStyleSup">52</span></a>&#46;</p><p id="par0090" class="elsevierStylePara elsevierViewall">Se ha demostrado la supresi&#243;n de la respuesta autoinmune tanto en las &#225;reas expuestas a la luz &#40;respondedoras&#41; como en las no expuestas &#40;no respondedoras&#41;&#46; Esto sugiere un modelo en el que los JAKi suprimen la respuesta inflamatoria Th1 y la fototerapia activa la regeneraci&#243;n melanocitica<a class="elsevierStyleCrossRef" href="#bib0755"><span class="elsevierStyleSup">51</span></a>&#46; Esta combinaci&#243;n requerir&#237;a de una menor dosis de exposici&#243;n lum&#237;nica&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Tofacitinib t&#243;pico</span><p id="par0095" class="elsevierStylePara elsevierViewall">En un estudio piloto&#44; presentan 16 pacientes con vit&#237;ligo no segmentario tratados con tofacitinib 2&#37; en crema con un tiempo medio de seguimiento de 153 d&#237;as &#40;rango 63-367&#41;&#44; de los cuales 13 experimentaron repigmentaci&#243;n&#46; Las respuestas fueron m&#225;s marcadas en lesiones faciales y en fototipos Fitzpatrick IV-VI&#44; mientras que el promedio de repigmentaci&#243;n en lesiones no faciales fue del 16&#37;<a class="elsevierStyleCrossRef" href="#bib0765"><span class="elsevierStyleSup">53</span></a>&#46; Uno de los pacientes present&#243; acn&#233; como efecto adverso&#46;</p><p id="par0100" class="elsevierStylePara elsevierViewall">Parece que tofacitinib t&#243;pico tambi&#233;n resultar&#237;a en mayor repigmentaci&#243;n con la exposici&#243;n a la luz&#46; En una serie de 11 pacientes con vit&#237;ligo facial tratados con tofacitinib 2&#37; t&#243;pico en crema 2 veces al d&#237;a junto con nb-UVB 3 veces a la semana entre 2 y 4 meses se observ&#243; una mejor&#237;a del 70&#37; en el VASI facial&#46; Los resultados indican una relaci&#243;n sin&#233;rgica aunque se necesitan estudios en vit&#237;ligo extrafacial<a class="elsevierStyleCrossRef" href="#bib0770"><span class="elsevierStyleSup">54</span></a>&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Ruxolitinib oral</span><p id="par0105" class="elsevierStylePara elsevierViewall">Ruxolitinib &#40;Jakavi&#174;&#44; Incyte&#47;Novartis&#41;&#44; un inhibidor JAK1&#47;2&#44; se utiliz&#243; para tratar a un var&#243;n con AA y vit&#237;ligo a dosis de 20<span class="elsevierStyleHsp" style=""></span>mg 2 veces al d&#237;a durante 20 semanas&#46; Inici&#243; repigmentaci&#243;n facial a las 12 semanas&#44; alcanzando un 51&#37; de pigmentaci&#243;n facial a las 20 semanas &#40;respecto al 0&#44;8&#37; basal&#41;<a class="elsevierStyleCrossRef" href="#bib0775"><span class="elsevierStyleSup">55</span></a>&#46;</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Ruxolitinib t&#243;pico</span><p id="par0110" class="elsevierStylePara elsevierViewall">Joshipura et al&#46;<a class="elsevierStyleCrossRef" href="#bib0780"><span class="elsevierStyleSup">56</span></a> describieron tasas de repigmentaci&#243;n superiores en los pacientes tratados con ruxolitinib 1&#44;5&#37; en crema 2 veces al d&#237;a en &#225;reas fotoexpuestas en comparaci&#243;n con las &#225;reas no fotoexpuestas&#46; Los pacientes con vit&#237;ligo que usaron ruxolitinib 1&#44;5&#37; en crema 2 veces al d&#237;a con nb-UVB opcional mostraron una mejor&#237;a estad&#237;sticamente significativa en el VASI score global a las 52 semanas&#44; con una respuesta especialmente pronunciada en el vit&#237;ligo facial&#46; La respuesta se mantuvo a los 6 meses de interrumpir el tratamiento<a class="elsevierStyleCrossRef" href="#bib0785"><span class="elsevierStyleSup">57</span></a>&#46;</p><p id="par0115" class="elsevierStylePara elsevierViewall">Actualmente&#44; existen ensayos cl&#237;nicos en curso que eval&#250;an la eficacia y seguridad de ruxolitinib t&#243;pico 1&#44;5&#37; en crema 2 veces al d&#237;a para tratamiento del vit&#237;ligo &#40;NCT04052425<a class="elsevierStyleCrossRef" href="#bib0790"><span class="elsevierStyleSup">58</span></a> y NCT04057573<a class="elsevierStyleCrossRef" href="#bib0795"><span class="elsevierStyleSup">59</span></a>&#41;&#44; y tambi&#233;n se est&#225; evaluando la respuesta con diferentes dosis &#40;NCT03099304<a class="elsevierStyleCrossRef" href="#bib0800"><span class="elsevierStyleSup">60</span></a>&#41;&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Otros inhibidores de JAK</span><p id="par0120" class="elsevierStylePara elsevierViewall">Hay un ensayo en curso con un inhibidor JAK1&#47;3 t&#243;pico &#40;ATI-50002&#41; en pacientes con vit&#237;ligo facial no segmentario &#40;NCT03468855<a class="elsevierStyleCrossRef" href="#bib0805"><span class="elsevierStyleSup">61</span></a>&#41;&#46; Tambi&#233;n se est&#225;n estudiando ritlecitinib &#40;inhibidor JAK3&#41; y brepocitinib &#40;inhibidor JAK1 y TYK2&#41; en pacientes con vit&#237;ligo no segmentario activo en combinaci&#243;n con fototerapia &#40;NCT03715829<a class="elsevierStyleCrossRef" href="#bib0810"><span class="elsevierStyleSup">62</span></a>&#41;&#46;</p></span></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Alopecia areata</span><p id="par0125" class="elsevierStylePara elsevierViewall">La patog&#233;nesis de la AA es compleja&#46; Las c&#233;lulas T V&#948;1&#43; podr&#237;an estar involucradas en los estadios precoces de la AA&#44; ya que se ha observado que tanto en los fol&#237;culos pilosos afectos como en los que a&#250;n no est&#225;n da&#241;ados el n&#250;mero de c&#233;lulas T V&#948;1&#43; es muy superior<a class="elsevierStyleCrossRef" href="#bib0815"><span class="elsevierStyleSup">63</span></a>&#46; Adem&#225;s existe evidencia de que las c&#233;lulas T citot&#243;xicas CD8&#43;NKG2D&#43; podr&#237;an ser clave en la patog&#233;nesis de la AA en modelos animales&#59; su objetivo ser&#237;an los fol&#237;culos que pierden el privilegio inmune durante la fase an&#225;gena<a class="elsevierStyleCrossRef" href="#bib0820"><span class="elsevierStyleSup">64</span></a>&#46; Las c&#233;lulas T CD8&#43;NKG2D&#43; producen IFN-&#947; que se une a su receptor en la superficie de los fol&#237;culos pilosos y activa la v&#237;a JAK1&#47;2-STAT1&#46; Esto promueve la producci&#243;n de IL-15&#44; que al unirse a su receptor en la superficie de las c&#233;lulas T activa JAK1&#47;3-STAT5&#44; generando la producci&#243;n de IFN-&#947; y perpetuando as&#237; la respuesta inflamatoria &#40;<a class="elsevierStyleCrossRef" href="#fig0010">fig&#46; 2</a>&#41;<a class="elsevierStyleCrossRef" href="#bib0825"><span class="elsevierStyleSup">65</span></a>&#46; Se ha visto sobreexpresi&#243;n de JAK3 y en menor medida de JAK1 y JAK2 en biopsias cut&#225;neas de pacientes con AA<a class="elsevierStyleCrossRef" href="#bib0680"><span class="elsevierStyleSup">36</span></a>&#46; De forma concomitante hay una sobrerregulaci&#243;n de diferentes citocinas &#8211;incluyendo IL-2&#44; IL-7 e IL-21&#8211; que se&#241;alizan a trav&#233;s de JAK1&#47;JAK3 y promueven la activaci&#243;n y la supervivencia de las c&#233;lulas T CD8&#43;NKG2D&#43;<a class="elsevierStyleCrossRef" href="#bib0820"><span class="elsevierStyleSup">64</span></a>&#46;</p><p id="par0130" class="elsevierStylePara elsevierViewall">Dado el papel de los JAK en la patog&#233;nesis de la AA&#44; los JAKi podr&#237;an ser efectivos para su tratamiento&#46; Adem&#225;s&#44; los JAKi podr&#237;an tener un efecto directo en los fol&#237;culos en fase tel&#243;gena&#44; promoviendo la reentrada en fase an&#225;gena<a class="elsevierStyleCrossRef" href="#bib0820"><span class="elsevierStyleSup">64</span></a>&#46;</p><p id="par0135" class="elsevierStylePara elsevierViewall">En un metaan&#225;lisis reciente<a class="elsevierStyleCrossRef" href="#bib0830"><span class="elsevierStyleSup">66</span></a> que incluye a 289 pacientes con AA se describe una tasa de respondedores del 72&#44;4&#37; con JAKi&#44; con un tiempo medio hasta el crecimiento completo de 6&#44;7 &#177; 2&#44;2 meses&#46; La v&#237;a oral fue m&#225;s efectiva que la t&#243;pica&#44; con una probabilidad de respuesta 4 veces superior&#46; Los pacientes con enfermedad de m&#225;s larga evoluci&#243;n presentar&#237;an menor respuesta a los JAKi<a class="elsevierStyleCrossRef" href="#bib0835"><span class="elsevierStyleSup">67</span></a>&#44; y la AA recidiva a los 3 meses de abandonar el tratamiento&#46; Se ha observado que algunas &#225;reas&#44; como las pesta&#241;as&#44; cejas&#44; barba y vello corporal&#44; presentan un recrecimiento m&#225;s r&#225;pido<a class="elsevierStyleCrossRefs" href="#bib0840"><span class="elsevierStyleSup">68&#8211;70</span></a>&#46;</p><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Tofacitinib oral</span><p id="par0140" class="elsevierStylePara elsevierViewall">La eficacia de tofacitinib oral en AA se describi&#243; por primera vez en un paciente con alopecia universal &#40;AU&#41; que inici&#243; tratamiento con tofacitinib 15<span class="elsevierStyleHsp" style=""></span>mg al d&#237;a para una psoriasis concomitante y experiment&#243; recrecimiento completo del pelo a los 8 meses de tratamiento<a class="elsevierStyleCrossRef" href="#bib0855"><span class="elsevierStyleSup">71</span></a>&#46; Desde entonces&#44; se han publicado respuestas en otros pacientes con AA<a class="elsevierStyleCrossRef" href="#bib0860"><span class="elsevierStyleSup">72</span></a>&#44; algunos de ellos con psoriasis<a class="elsevierStyleCrossRef" href="#bib0865"><span class="elsevierStyleSup">73</span></a>&#44; DA o vit&#237;ligo concomitantes<a class="elsevierStyleCrossRefs" href="#bib0750"><span class="elsevierStyleSup">50&#44;74</span></a>&#44; con mejor&#237;a simult&#225;nea de ambas enfermedades&#46;</p><p id="par0145" class="elsevierStylePara elsevierViewall">Posteriormente en un estudio abierto de 66 pacientes con AA y p&#233;rdida superior al 50&#37;&#44; alopecia total &#40;AT&#41; o AU&#44; tofacitinib 5<span class="elsevierStyleHsp" style=""></span>mg 2 veces al d&#237;a durante 3 meses consigui&#243; cambios en la puntuaci&#243;n <span class="elsevierStyleItalic">Severity of Alopecia Tool</span> &#40;SALT&#41; comprendidos entre el 5&#37; y el 50&#37; en el 32&#37; de los pacientes y de<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>50&#37; de puntuaci&#243;n SALT en un 32&#37;&#46; Sin embargo&#44; la duraci&#243;n promedio de la respuesta hasta la reca&#237;da tras suspender el tratamiento era de 8&#44;5 semanas&#46; El 25&#44;8&#37; de los pacientes desarrollaron infecciones&#44; la mayor&#237;a del tracto respiratorio superior aunque describen 2 pacientes con infecciones del tracto urinario&#44; un paciente desarroll&#243; una bronquitis y otro un herpes z&#243;ster&#46; Ninguno de ellos requiri&#243; hospitalizaci&#243;n<a class="elsevierStyleCrossRef" href="#bib0875"><span class="elsevierStyleSup">75</span></a>&#46;</p><p id="par0150" class="elsevierStylePara elsevierViewall">Cheng et al&#46;<a class="elsevierStyleCrossRef" href="#bib0880"><span class="elsevierStyleSup">76</span></a> publicaron los casos de 11 pacientes con AT&#47;AU tratados con tofacitinib a dosis de entre 5<span class="elsevierStyleHsp" style=""></span>mg al d&#237;a a 11<span class="elsevierStyleHsp" style=""></span>mg &#8211;con un preparado de liberaci&#243;n prolongada&#8211; 2 veces al d&#237;a durante una media de 14&#44;4 meses &#40;rango 4&#44;5-27 meses&#41;&#44; consiguiendo una mejor&#237;a promedio del SALT del 61&#44;2&#37; con respecto al valor basal&#46; La mitad de los pacientes consiguieron una resoluci&#243;n completa de la enfermedad y algunos se beneficiaron de la combinaci&#243;n con triamcinolona intralesional en &#225;reas refractarias&#46; Como efectos adversos observaron dislipidemia&#44; s&#237;ntomas gastrointestinales y acn&#233; leve&#46;</p><p id="par0155" class="elsevierStylePara elsevierViewall">Liu et al&#46;<a class="elsevierStyleCrossRef" href="#bib0835"><span class="elsevierStyleSup">67</span></a> incluyeron en un estudio retrospectivo a 90 pacientes con AA afectando un 40&#37; o m&#225;s del cuero cabelludo&#44; AT o AU&#44; a los que trataron con tofacitinib por lo menos 5<span class="elsevierStyleHsp" style=""></span>mg 2 veces al d&#237;a en monoterapia o combinado con prednisona durante un m&#237;nimo de 4 meses&#46; De los 65 de estos pacientes que se consideraron respondedores potenciales por padecer AT&#47;AU menos de 10 a&#241;os o AA&#44; el 20&#37; mostraron una reducci&#243;n superior al 90&#37; en la puntuaci&#243;n SALT&#44; un 38&#44;4&#37; presentaron una reducci&#243;n del 51-90&#37; en el SALT y el 18&#44;5&#37; presentaron una reducci&#243;n en SALT de 6-50&#37;&#46; El efecto adverso m&#225;s frecuente fueron las infecciones del tracto respiratorio superior que se dieron en el 28&#44;9&#37; de los pacientes&#44; aunque tambi&#233;n describen a un paciente con bronquitis y 3 con infecciones del tracto urinario&#46;</p><p id="par0160" class="elsevierStylePara elsevierViewall">Recientemente&#44; en otro estudio en 12 pacientes con AA moderada-severa&#44; AT o AU&#44; en la mayor&#237;a de los casos fue preciso aumentar la dosis de tofacitinib de 5<span class="elsevierStyleHsp" style=""></span>mg&#47;12<span class="elsevierStyleHsp" style=""></span>h a 10<span class="elsevierStyleHsp" style=""></span>mg&#47;12<span class="elsevierStyleHsp" style=""></span>h para conseguir respuesta&#44; sin que se observara un aumento de los efectos adversos&#46; El 91&#44;7&#37; de los pacientes tuvieron respuesta&#44; con un promedio de reducci&#243;n del SALT del 56&#44;8&#37; a las 32 semanas&#46; Sin embargo&#44; al retirar el tratamiento en los pacientes respondedores&#44; el 50&#37; empeoraron con respecto a los valores basales tras 6 meses de observaci&#243;n<a class="elsevierStyleCrossRef" href="#bib0885"><span class="elsevierStyleSup">77</span></a>&#46; Se han publicado m&#250;ltiples ejemplos de pacientes con respuesta inicial pero sin mantenimiento de la respuesta al interrumpir el tratamiento<a class="elsevierStyleCrossRefs" href="#bib0840"><span class="elsevierStyleSup">68&#44;78&#44;79</span></a>&#44; volviendo a niveles de alopecia similares o incluso peores al basal<a class="elsevierStyleCrossRef" href="#bib0900"><span class="elsevierStyleSup">80</span></a>&#46; No queda claro si se trata de un aumento de actividad de la enfermedad o si la retirada del tratamiento desencadena un efluvio tel&#243;geno&#44; ya que los JAKi promueven el pase de los fol&#237;culos a la fase an&#225;gena<a class="elsevierStyleCrossRef" href="#bib0905"><span class="elsevierStyleSup">81</span></a>&#46;</p><p id="par0165" class="elsevierStylePara elsevierViewall">Por lo que respecta a la poblaci&#243;n pedi&#225;trica y adolescentes&#44; se han publicado casos de AT y AU tratados satisfactoriamente con tofacitinib 5<span class="elsevierStyleHsp" style=""></span>mg&#47;12<span class="elsevierStyleHsp" style=""></span>h&#44; sin efectos adversos destacables<a class="elsevierStyleCrossRefs" href="#bib0910"><span class="elsevierStyleSup">82&#44;83</span></a>&#46;</p><p id="par0170" class="elsevierStylePara elsevierViewall">Actualmente se est&#225; llevando a cabo un estudio de cohorte para evaluar la eficacia y seguridad de tofacitinib 5<span class="elsevierStyleHsp" style=""></span>mg 2 veces al d&#237;a junto con el impacto econ&#243;mico que supondr&#237;a el cambio en la calidad de vida del paciente con AA extensa &#40;NCT03800979<a class="elsevierStyleCrossRef" href="#bib0920"><span class="elsevierStyleSup">84</span></a>&#41;&#46;</p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Tofacitinib t&#243;pico</span><p id="par0175" class="elsevierStylePara elsevierViewall">Los inhibidores de JAK t&#243;picos podr&#237;an ser &#250;tiles especialmente para el tratamiento de la AA localizada&#46; Se ha observado crecimiento casi completo del pelo despu&#233;s de usar tofacitinib 2&#37; t&#243;pico cada 12<span class="elsevierStyleHsp" style=""></span>h durante 7 meses<a class="elsevierStyleCrossRef" href="#bib0880"><span class="elsevierStyleSup">76</span></a>&#44; y de las pesta&#241;as tras una media de 7 meses de tratamiento &#40;rango 3-11 meses&#41;<a class="elsevierStyleCrossRef" href="#bib0695"><span class="elsevierStyleSup">39</span></a>&#44; sin efectos adversos&#46; Sin embargo&#44; en un estudio piloto con 10 pacientes tratados con tofacitinib pomada 2&#37; 2 veces al d&#237;a la respuesta fue pobre&#44; con &#250;nicamente 3 respondedores con una disminuci&#243;n media del SALT del 34&#44;6&#37; a las 24 semanas<a class="elsevierStyleCrossRef" href="#bib0685"><span class="elsevierStyleSup">37</span></a>&#46; Los efectos adversos observados fueron irritaci&#243;n local &#40;40&#37;&#41;&#44; foliculitis &#40;10&#37;&#41; y elevaci&#243;n del colesterol &#40;40&#37;&#41;&#46;</p><p id="par0180" class="elsevierStylePara elsevierViewall">Tambi&#233;n se ha descrito la eficacia de tofacitinib en pomada al 1-2&#37; en un grupo de ni&#241;os y adolescentes usado durante 3-9 meses&#44; sin efectos adversos destacables<a class="elsevierStyleCrossRef" href="#bib0670"><span class="elsevierStyleSup">34</span></a>&#46; Adem&#225;s&#44; con tofacitinib al 2&#37; en base liposomal se obtuvo una respuesta variable en 11 pacientes pedi&#225;tricos&#44; aunque la mayor&#237;a consigui&#243; una respuesta cosm&#233;ticamente aceptable&#44; por lo que se podr&#237;a usar como tratamiento adyuvante o como tratamiento de segunda l&#237;nea en estos pacientes<a class="elsevierStyleCrossRef" href="#bib0690"><span class="elsevierStyleSup">38</span></a>&#46;</p></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Ruxolitinib oral</span><p id="par0185" class="elsevierStylePara elsevierViewall">Una mujer tratada con ruxolitinib oral 15<span class="elsevierStyleHsp" style=""></span>mg 2 veces al d&#237;a por trombocitopenia experiment&#243; repoblamiento casi completo de su AU a los 10 meses&#44; manteniendo la respuesta con el tratamiento a los 50 meses<a class="elsevierStyleCrossRef" href="#bib0925"><span class="elsevierStyleSup">85</span></a>&#46; Otro paciente con AA y vit&#237;ligo mostr&#243; mejor&#237;a de las 2 condiciones con ruxolitinib 20<span class="elsevierStyleHsp" style=""></span>mg 2 veces al d&#237;a&#44; con inicio del crecimiento del pelo a las 4 semanas y mejor&#237;a significativa a las 12 semanas<a class="elsevierStyleCrossRef" href="#bib0775"><span class="elsevierStyleSup">55</span></a>&#46;</p><p id="par0190" class="elsevierStylePara elsevierViewall">En un estudio realizado con 12 pacientes tratados con ruxolitinib 20<span class="elsevierStyleHsp" style=""></span>mg&#47;12<span class="elsevierStyleHsp" style=""></span>h durante 3-6 meses&#44; el 75&#37; consiguieron respuesta&#44; pasando de un SALT inicial promedio del 65&#44;8&#37; a un SALT del 7&#44;3&#37; a los 6 meses de tratamiento&#46; La mayor&#237;a de los respondedores tuvieron un recrecimiento del 95&#37;&#44; que fue notorio a las 4 semanas del tratamiento<a class="elsevierStyleCrossRef" href="#bib0930"><span class="elsevierStyleSup">86</span></a>&#46; Sin embargo&#44; a las 3 semanas de suspender el tratamiento se perdi&#243; la respuesta&#46; Los efectos adversos m&#225;s frecuentes fueron las infecciones de v&#237;as respiratorias altas&#44; aunque describen un caso de neumon&#237;a leve&#46; Se ha empleado la misma dosis para el tratamiento de un var&#243;n preadolescente con AT<a class="elsevierStyleCrossRef" href="#bib0935"><span class="elsevierStyleSup">87</span></a>&#46; A los 4 meses&#44; present&#243; pr&#225;cticamente recrecimiento completo de cejas y cuero cabelludo por lo que se pudo disminuir la dosis hasta alcanzar 10<span class="elsevierStyleHsp" style=""></span>mg a d&#237;as alternos sin p&#233;rdida de eficacia&#46; Ruxolitinib 30<span class="elsevierStyleHsp" style=""></span>mg diarios tambi&#233;n se ha asociado a recrecimiento completo del pelo a los 8 meses en una paciente con AT&#44; con disminuci&#243;n progresiva de la dosis sin p&#233;rdida de respuesta y con desarrollo de anemia transitoria al inicio del tratamiento<a class="elsevierStyleCrossRef" href="#bib0940"><span class="elsevierStyleSup">88</span></a>&#46;</p><p id="par0195" class="elsevierStylePara elsevierViewall">A pesar de que ruxolitinib 20<span class="elsevierStyleHsp" style=""></span>mg 2 veces al d&#237;a y tofacitinib 5<span class="elsevierStyleHsp" style=""></span>mg 2 veces al d&#237;a no muestran diferencias significativas por lo que respecta al recrecimiento a los 6 meses del tratamiento o la tasa de reca&#237;da&#44; el recrecimiento inicial con ruxolitinib parece ser m&#225;s precoz<a class="elsevierStyleCrossRef" href="#bib0945"><span class="elsevierStyleSup">89</span></a>&#46;</p></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Ruxolitinib t&#243;pico</span><p id="par0200" class="elsevierStylePara elsevierViewall">Se han observado respuestas variables con ruxolitinib 0&#44;6-2&#37; t&#243;pico<a class="elsevierStyleCrossRefs" href="#bib0675"><span class="elsevierStyleSup">35&#44;90</span></a>&#46; En un ensayo prospectivo en fase <span class="elsevierStyleSmallCaps">i</span> a las 28 semanas se observ&#243; recrecimiento parcial en 5 pacientes con AU en las &#225;reas tratadas con ruxolitinib 1&#37; t&#243;pico<a class="elsevierStyleCrossRef" href="#bib0955"><span class="elsevierStyleSup">91</span></a>&#46;</p><p id="par0205" class="elsevierStylePara elsevierViewall">Una adolescente con AA universal aplic&#243; crema 0&#44;6&#37; 2 veces al d&#237;a&#44; consiguiendo crecimiento completo de las cejas a los 3 meses pero con &#250;nicamente 10&#37; de recrecimiento en cuero cabelludo&#44; sin presentar efectos adversos&#46; En pacientes pedi&#225;tricos&#44; se ha visto que la formulaci&#243;n liposomal es m&#225;s efectiva&#44; pero la no liposomal es cosm&#233;ticamente m&#225;s aceptable<a class="elsevierStyleCrossRef" href="#bib0670"><span class="elsevierStyleSup">34</span></a>&#46;</p></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Baricitinib oral</span><p id="par0210" class="elsevierStylePara elsevierViewall">Baricitinib &#40;Olumiant&#174;&#44; Eli Lilly and Company&#41; es un inhibidor JAK1&#47;2&#46; Se ha observado crecimiento completo del pelo en un paciente con AA ofi&#225;sica a los 9 meses del inicio de baricitinib oral 7<span class="elsevierStyleHsp" style=""></span>mg por la ma&#241;ana y 4<span class="elsevierStyleHsp" style=""></span>mg por la noche para el tratamiento de un s&#237;ndrome de CANDLE concomitante<a class="elsevierStyleCrossRef" href="#bib0960"><span class="elsevierStyleSup">92</span></a>&#46;</p></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Otros inhibidores de JAK</span><p id="par0215" class="elsevierStylePara elsevierViewall">Un estudio que comparaba el uso de pomada de delgocitinib &#40;inhibidor pan-JAK&#41; 30<span class="elsevierStyleHsp" style=""></span>mg&#47;g 2 veces al d&#237;a con veh&#237;culo para el tratamiento de AA no encontr&#243; diferencias estad&#237;sticamente significativas en la reducci&#243;n del SALT a las 12 semanas &#40;NCT02561585&#41;<a class="elsevierStyleCrossRef" href="#bib0965"><span class="elsevierStyleSup">93</span></a>&#46;</p><p id="par0220" class="elsevierStylePara elsevierViewall">Un ensayo fase IIA evalu&#243; la eficacia de ritlecitinib y de brepocitinib en 142 pacientes con AA moderada a severa &#40;NCT02974868<a class="elsevierStyleCrossRef" href="#bib0970"><span class="elsevierStyleSup">94</span></a>&#41;&#46; A las 6 semanas de tratamiento con brepocitinib y ritlecitinib la diferencia media en el SALT score respecto al basal era de 12&#44;44&#37; y 19&#44;36&#37;&#44; respectivamente&#44; comparado con 1&#44;32&#37; del grupo placebo&#46; A las 24 semanas de tratamiento&#44; los respondedores presentaron un recrecimiento completo&#46;</p><p id="par0225" class="elsevierStylePara elsevierViewall">Se est&#225; ensayando otro inhibidor JAK1 &#40;SHR0302&#41; en adultos con AA moderada a severa &#40;NCT04346316&#41;<a class="elsevierStyleCrossRef" href="#bib0975"><span class="elsevierStyleSup">95</span></a>&#46;</p></span></span><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Conclusiones</span><p id="par0230" class="elsevierStylePara elsevierViewall">Existe evidencia de que la disregulaci&#243;n de la v&#237;a JAK-STAT podr&#237;a desempe&#241;ar un papel en muchas enfermedades dermatol&#243;gicas&#44; incluyendo el vit&#237;ligo y la AA&#46;</p><p id="par0235" class="elsevierStylePara elsevierViewall">Los inhibidores de JAK orales y t&#243;picos podr&#237;an ser una opci&#243;n prometedora para el tratamiento del vit&#237;ligo&#44; aunque los resultados apuntan a que es preciso el tratamiento adyuvante con nb-UVB o la luz solar para obtener resultados satisfactorios&#46;</p><p id="par0240" class="elsevierStylePara elsevierViewall">Existe evidencia creciente de que los JAKi podr&#237;an ser eficaces para el tratamiento de la AA&#44; con un perfil riesgo-beneficio aceptable&#46; Se han estudiado tofacitinib&#44; ruxolitinib y baricitinib&#44; con resultados variables&#46; Sin embargo&#44; los JAKi ser&#237;an un tratamiento sintom&#225;tico en AA ya que las reca&#237;das al interrumpir el tratamiento son habituales&#46; El tratamiento t&#243;pico con JAKi podr&#237;a ser una alternativa en caso de enfermedad localizada&#44; de aparici&#243;n de efectos adversos con el tratamiento oral o en pacientes pedi&#225;tricos&#46;</p><p id="par0245" class="elsevierStylePara elsevierViewall">Los JAKi se han empleado tambi&#233;n para el tratamiento de otras patolog&#237;as dermatol&#243;gicas como la psoriasis o la DA&#44; que se desarrollar&#225;n en detalle en la parte 2 de esta revisi&#243;n&#46;</p></span><span id="sec0085" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Conflicto de intereses</span><p id="par0250" class="elsevierStylePara elsevierViewall">C&#46; Garcia-Melendo y X&#46; Cubir&#243; declaran no tener conflicto de intereses&#46; L&#46; Puig ha recibido honorarios de&#47;ha participado en ensayos cl&#237;nicos patrocinados por Abbvie&#44; Almirall&#44; Amgen&#44; Baxalta&#44; Biogen&#44; Boehringer Ingelheim&#44; Celgene&#44; Gebro&#44; Janssen&#44; JS BIOCAD&#44; Leo-Pharma&#44; Lilly&#44; Merck-Serono&#44; MSD&#44; Mylan&#44; Novartis&#44; Pfizer&#44; Regeneron&#44; Roche&#44; Sandoz&#44; Samsung-Bioepis&#44; Sanofi y UCB&#46;</p></span></span>"
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        "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">La v&#237;a de se&#241;alizaci&#243;n de citocinas Janus cinasa&#47;transductor de se&#241;al y activador de transcripci&#243;n &#40;JAK&#47;STAT&#41; es un &#225;rea de inter&#233;s emergente en dermatolog&#237;a&#44; con evidencia creciente del papel clave en la patog&#233;nesis de las enfermedades inflamatorias cut&#225;neas&#46; Debido a que algunas citocinas proinflamatorias usan la v&#237;a JAK&#47;STAT para la transducci&#243;n de se&#241;ales&#44; esta se convierte en una diana terap&#233;utica prometedora para el tratamiento de dichas enfermedades&#44; al modular de forma selectiva el sistema inmune&#46;</p><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">El objetivo de esta revisi&#243;n es conocer la v&#237;a de se&#241;alizaci&#243;n JAK&#47;STAT y su papel en distintas enfermedades dermatol&#243;gicas inmunomediadas&#46; En esta primera parte&#44; se revisar&#225; la eficacia y seguridad de los inhibidores de JAK &#8211;en formulaci&#243;n oral o t&#243;pica&#8211; para el tratamiento del vit&#237;ligo y la alopecia areata&#46;</p></span>"
      ]
      "en" => array:2 [
        "titulo" => "Abstract"
        "resumen" => "<span id="abst0015" class="elsevierStyleSection elsevierViewall"><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Dermatologists&#8217; interest in the Janus-associated kinase&#47;signal transducers and activators of transcription &#40;JAK&#47;STAT&#41; pathway has been growing as evidence builds to support its key role in the pathogenesis of inflammatory skin diseases&#46; Because certain proinflammatory cytokines use the JAK&#47;STAT pathway for signal transduction&#44; it has become a promising therapeutic target in diseases where selective modulation of the immune system can be useful&#46;</p><p id="spar0095" class="elsevierStyleSimplePara elsevierViewall">We aim to review current knowledge of the JAK&#47;STAT signaling pathway and its role in immune-mediated skin diseases&#46; In the first part of the review we cover the efficacy and safety of oral and topical JAK inhibitors in the treatment of vitiligo and alopecia areata&#46;</p></span>"
      ]
    ]
    "multimedia" => array:6 [
      0 => array:7 [
        "identificador" => "fig0005"
        "etiqueta" => "Figura 1"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr1.jpeg"
            "Alto" => 2086
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        "descripcion" => array:1 [
          "es" => "<p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">V&#237;a JAK&#47;STAT y mecanismo de acci&#243;n de los inhibidores JAK&#46;</p> <p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">A&#41; V&#237;a JAK&#47;STAT&#46; La citoquina se une al receptor activando las prote&#237;nas JAK mediante fosforilaci&#243;n&#46; El JAK activado fosforila prote&#237;na STAT&#44; activ&#225;ndola&#46; STAT activado se transloca al n&#250;cleo&#46; La prote&#237;na STAT activada act&#250;a como un factor de transcripci&#243;n y se une al ADN&#44; regulando la transcripci&#243;n de una gran variedad de genes afectando el crecimiento celular y la apoptosis&#46; B&#41; Mecanismo de acci&#243;n de los inhibidores de JAK &#40;JAKi&#41;&#46; Los inhibidores de JAK se unen al sitio de uni&#243;n del adenos&#237;n trifosfato del d&#237;mero JAK impidiendo su autofosforilaci&#243;n y activaci&#243;n&#46; Sin la activaci&#243;n de JAK&#44; la prote&#237;na STAT tampoco se puede activar ni translocar al n&#250;cleo&#44; resultando en una menor transcripci&#243;n de genes proinflamatorios&#46; Figura creada con ayuda de Biorender&#46;com&#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"
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        "descripcion" => array:1 [
          "es" => "<p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Receptores de citoquinas y selectividad de los inhibidores de JAK en dermatolog&#237;a&#46;</p> <p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Los diferentes receptores de citocinas se asocian a diferentes JAK&#44; las cuales transducen intracelularmente las se&#241;ales del ligando extracelular&#46; Los JAKi tienen diferentes capacidades de bloquear la se&#241;alizaci&#243;n de los receptores de citocinas&#58; los inhibidores no selectivos inhiben muchas citocinas a la vez&#44; mientras que los JAKi m&#225;s selectivos inhiben una funci&#243;n biol&#243;gica espec&#237;fica pero permiten la se&#241;alizaci&#243;n de otras citocinas por otras v&#237;as dependientes de JAK&#46;</p> <p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">AA&#58; alopecia areata&#59; DA&#58; dermatitis at&#243;pica&#59; EPO&#58; eritropoyetina&#59; G-CSF&#58; factor estimulante de colonias de granulocitos&#59; GH&#58; hormona de crecimiento&#59; GM-CSF&#58; factor estimulante de las colonias de granulocitos macr&#243;fagos&#59; IFN-&#945;&#58; interfer&#243;n-alfa&#59; IFN-&#946;&#58; interfer&#243;n-beta&#59; IFN-<span class="elsevierStyleItalic">&#947;</span>&#58; interfer&#243;n-gamma&#59; TPO&#58; trombopoyetina&#46;</p> <p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Figura creada con ayuda de Biorender&#46;com&#46;</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:2 [
          "leyenda" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">EPO&#58; eritropoyetina&#59; G-CSF&#58; factor estimulante de colonias de granulocitos&#59; GH&#58; hormona de crecimiento&#59; GM-CSF&#58; factor estimulante de las colonias de granulocitos macr&#243;fagos&#59; IFN-&#945;&#58; interfer&#243;n-alfa&#59; IFN-&#946;&#58; interfer&#243;n-beta&#59; IFN-<span class="elsevierStyleItalic">&#947;</span>&#58; interfer&#243;n-gamma<span class="elsevierStyleItalic">&#59;</span> TPO&#58; trombopoyetina&#46;</p><p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">Todos los miembros de la familia JAK se expresan de forma ubicua en mam&#237;feros&#44; excepto JAK3 que se expresa principalmente en tejido linfoide y hematopoy&#233;tico&#46; Cada miembro de la familia JAK dimeriza con otro miembro de la misma familia&#44; y es activado tras la uni&#243;n de determinadas citocinas a los receptores transmembrana&#46; IFN-<span class="elsevierStyleItalic">&#947;</span>&#44; por ejemplo&#44; es dependiente de la se&#241;alizaci&#243;n JAK1&#47;JAK2 y participa en la diferenciaci&#243;n de c&#233;lulas T&#44; la funci&#243;n efectora de linfocitos y la activaci&#243;n de macr&#243;fagos&#46; JAK2&#47;JAK2 participan en la diferenciaci&#243;n mieloide y linfoide&#44; proliferaci&#243;n y supervivencia de c&#233;lulas T&#44; funci&#243;n efectora de los linfocitos&#44; hematopoyesis&#44; crecimiento y metabolismo anab&#243;lico&#46; JAK2&#47; TYK2 intervienen en la diferenciaci&#243;n de c&#233;lulas T y la funci&#243;n efectora de los linfocitos&#46; JAK1&#47;JAK3 participan en la proliferaci&#243;n y supervivencia de c&#233;lulas T y c&#233;lulas T de memoria y la funci&#243;n de las c&#233;lulas T reguladoras&#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  " colspan="5" align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Citocinas activadoras y dimerizaci&#243;n de la familia de las Janus cinasas</th></tr><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&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">JAK1&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">JAK2&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">JAK3&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">TYK2&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-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">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">No dimerizan&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">IFN-<span class="elsevierStyleItalic">&#947;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\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-2&#44; IL-4&#44; IL-7&#44; IL-9&#44; IL-15&#44; IL-21&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">IFN- &#945;&#44; IFN- &#946;&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">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">IFN-<span class="elsevierStyleItalic">&#947;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\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-3&#44; IL-5&#44; GM-CSF&#44; EPO&#44; TPO&#44; G-CSF&#44; GH&#44; leptina&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\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 dimerizan&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\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&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">JAK3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\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-2&#44; IL-4&#44; IL-7&#44; IL-9&#44; IL-15&#44; IL-21&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\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 dimerizan&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\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 dimerizan&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\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 dimerizan&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">TYK2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">IFN- &#945;&#44; IFN- &#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">IL-12&#44; IL-23&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\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 dimerizan&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\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 dimerizan&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
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        ]
        "descripcion" => array:1 [
          "es" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Familia de Janus cinasas &#40;JAK&#41;</p>"
        ]
      ]
      3 => array:8 [
        "identificador" => "tbl0010"
        "etiqueta" => "Tabla 2"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at2"
            "detalle" => "Tabla "
            "rol" => "short"
          ]
        ]
        "tabla" => array:2 [
          "leyenda" => "<p id="spar0075" class="elsevierStyleSimplePara elsevierViewall">IC50&#58; concentraci&#243;n del f&#225;rmaco que produce un 50&#37; de inhibici&#243;n&#59; JAK&#58; Janus cinasa&#46;</p><p id="spar0080" class="elsevierStyleSimplePara elsevierViewall">En la tabla se muestran los valores IC50 para la inhibici&#243;n de JAK1&#44; JAK2&#44; JAK3 y TYK2 por los diferentes inhibidores JAK con aplicaciones dermatol&#243;gicas<a class="elsevierStyleCrossRefs" href="#bib0510"><span class="elsevierStyleSup">2&#44;96&#44;97</span></a>&#46; Gusacitinib &#40;ASN002&#41; al ser un inhibidor de SYK&#44; JAK1&#44; JAK2&#44; JAK3 y TYK2 no se representa en la tabla&#59; tiene valores IC50 de 5&#44; 46&#44; 4&#44; 11 y 8<span class="elsevierStyleHsp" style=""></span>nM&#44; respectivamente<a class="elsevierStyleCrossRefs" href="#bib0990"><span class="elsevierStyleSup">98&#44;99</span></a>&#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="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&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">JAK1&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">JAK2&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">JAK3&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">TYK2&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-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">Tofacitinib &#40;Xeljanz&#174;&#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">5&#44;9<span class="elsevierStyleHsp" style=""></span>nM&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">20<span class="elsevierStyleHsp" style=""></span>nM&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1<span class="elsevierStyleHsp" style=""></span>nM&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">34<span class="elsevierStyleHsp" style=""></span>nM&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">Ruxolitinib &#40;Jakavi&#174;&#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">3&#44;3<span class="elsevierStyleHsp" style=""></span>nM&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">2&#44;8<span class="elsevierStyleHsp" style=""></span>nM&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">390<span class="elsevierStyleHsp" style=""></span>nM&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">18<span class="elsevierStyleHsp" style=""></span>nM&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">Baricitinib &#40;Olumiant&#174;&#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
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                  \t\t\t\t">5&#44;9<span class="elsevierStyleHsp" style=""></span>nM&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">5&#44;7<span class="elsevierStyleHsp" style=""></span>nM&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">420<span class="elsevierStyleHsp" style=""></span>nM&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">53<span class="elsevierStyleHsp" style=""></span>nM&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">Peficitinib &#40;Smyraf&#174;&#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
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                  \t\t\t\t">3&#44;9<span class="elsevierStyleHsp" style=""></span>nM&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">5<span class="elsevierStyleHsp" style=""></span>nM&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#44;7<span class="elsevierStyleHsp" style=""></span>nM&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">4&#44;8<span class="elsevierStyleHsp" style=""></span>nM&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">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
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                  \t\t\t\t">29<span class="elsevierStyleHsp" style=""></span>nM&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">803<span class="elsevierStyleHsp" style=""></span>nM&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">&#62;<span class="elsevierStyleHsp" style=""></span>10&#46;000<span class="elsevierStyleHsp" style=""></span>nM&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">1253<span class="elsevierStyleHsp" style=""></span>nM&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;Rinvoq&#174;&#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">43<span class="elsevierStyleHsp" style=""></span>nM&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">200<span class="elsevierStyleHsp" style=""></span>nM&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">2300<span class="elsevierStyleHsp" style=""></span>nM&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">4700<span class="elsevierStyleHsp" style=""></span>nM&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">Delgocitinib &#40;Corectim&#174;&#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
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                  \t\t\t\t">2&#44;8<span class="elsevierStyleHsp" style=""></span>nM&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">2&#44;6<span class="elsevierStyleHsp" style=""></span>nM&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">13<span class="elsevierStyleHsp" style=""></span>nM&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">58<span class="elsevierStyleHsp" style=""></span>nM&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">Brepocitinib &#40;PF-06700841&#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
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                  \t\t\t\t">17<span class="elsevierStyleHsp" style=""></span>nM&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">77<span class="elsevierStyleHsp" style=""></span>nM&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">6490<span class="elsevierStyleHsp" style=""></span>nM&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">23<span class="elsevierStyleHsp" style=""></span>nM&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
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                  \t\t\t\t">ATI50002&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">2<span class="elsevierStyleHsp" style=""></span>nM&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">-&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">36<span class="elsevierStyleHsp" style=""></span>nM&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \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">Ritlecitinib &#40;PF-06651600&#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
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                  \t\t\t\t">&#62;<span class="elsevierStyleHsp" style=""></span>10&#46;000<span class="elsevierStyleHsp" style=""></span>nM&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">&#62;<span class="elsevierStyleHsp" style=""></span>10&#46;000<span class="elsevierStyleHsp" style=""></span>nM&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">33&#44;1<span class="elsevierStyleHsp" style=""></span>nM&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">&#62;<span class="elsevierStyleHsp" style=""></span>10&#46;000<span class="elsevierStyleHsp" style=""></span>nM&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">Itacitinib &#40;INCB-039110&#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
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                  \t\t\t\t">2<span class="elsevierStyleHsp" style=""></span>nM&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">63<span class="elsevierStyleHsp" style=""></span>nM&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">&#62;<span class="elsevierStyleHsp" style=""></span>2000<span class="elsevierStyleHsp" style=""></span>nM&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">795<span class="elsevierStyleHsp" style=""></span>nM&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">Solcitinib &#40;GSK-2586184&#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
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                  \t\t\t\t">108<span class="elsevierStyleHsp" style=""></span>nM&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">539<span class="elsevierStyleHsp" style=""></span>nM&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">225<span class="elsevierStyleHsp" style=""></span>nM&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Filgotinib&#40;G-146034&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">10<span class="elsevierStyleHsp" style=""></span>nM&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">810<span class="elsevierStyleHsp" style=""></span>nM&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">SHR0302&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">INCB054707&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">463<span class="elsevierStyleHsp" style=""></span>nM&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \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
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                  \t\t\t\t">-&nbsp;\t\t\t\t\t\t\n
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                  \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">Deucravacitinib &#40;BMS-986165&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">-&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="\n
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                  \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
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#44;02<span class="elsevierStyleHsp" style=""></span>nM&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
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">PF-06826647&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">383<span class="elsevierStyleHsp" style=""></span>nM&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">74<span class="elsevierStyleHsp" style=""></span>nM&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">&#62;<span class="elsevierStyleHsp" style=""></span>10&#46;000<span class="elsevierStyleHsp" style=""></span>nM&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">14&#44;9<span class="elsevierStyleHsp" style=""></span>nM&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
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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">Nombre&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">F&#243;rmula&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">Aprobaci&#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">Aplicaciones en dermatolog&#237;a&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-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">TofacitinibCP-690550&#40;Xeljanz&#174;&#44; Pfizer&#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">JAK1JAK3JAK2<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>TYK2<span class="elsevierStyleSup">a&#42;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">C16H20N6O&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Oral&#47;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">Artritis reumatoide &#40;FDA 2012&#44; EMA 2017&#41;&#58; 5<span class="elsevierStyleHsp" style=""></span>mg 2 veces al d&#237;aArtritis psori&#225;sica &#40;FDA 2017 y EMA 2018&#41;&#58; 5<span class="elsevierStyleHsp" style=""></span>mg 2 veces al d&#237;aArtritis idiop&#225;tica juvenil poliarticular &#40;FDA&#44; 2020&#41;&#58; dosis seg&#250;n pesoColitis ulcerosa &#40;FDA y EMA 2018&#41;&#58; 10<span class="elsevierStyleHsp" style=""></span>mg 2 veces al d&#237;a 8 semanas seguido de 5<span class="elsevierStyleHsp" style=""></span>mg 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">Psoriasis &#40;oral&#44; t&#243;pico&#41;Alopecia areata &#40;oral&#44; t&#243;pico&#41;Dermatitis at&#243;pica &#40;oral&#44; t&#243;pico&#41;Vit&#237;ligo &#40;oral&#44; t&#243;pico&#41;Hidradenitis supurativa &#40;oral&#41;Liquen plano &#40;oral&#41;Dermatomiositis &#40;oral&#41;Sarcoidosis cut&#225;nea &#40;oral&#41;Granuloma anular generalizado &#40;oral&#41;Pioderma gangrenoso &#40;oral&#41;&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">RuxolitinibINCB-018424&#40;Jakavi&#174;&#44; Incyte&#47;Novartis&#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">JAK1JAK2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">C17H18N6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Oral&#47;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">Mielofibrosis &#40;FDA 2011&#44; EMA 2012&#41;&#58; 15 o 20<span class="elsevierStyleHsp" style=""></span>mg 2 veces al d&#237;aPolicitemia vera &#40;FDA&#44; 2014&#44; EMA 2015&#41;&#58; 10<span class="elsevierStyleHsp" style=""></span>mg 2 veces al d&#237;aEnfermedad injerto contra hu&#233;sped &#40;FDA 2019&#41;&#58; 5<span class="elsevierStyleHsp" style=""></span>mg 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">Psoriasis &#40;t&#243;pico&#41;Vit&#237;ligo &#40;oral&#44; t&#243;pico&#41;Alopecia areata &#40;oral&#44; t&#243;pico&#41;Dermatitis at&#243;pica &#40;t&#243;pico&#41;Dermatomiositis &#40;oral&#41;Lupus cut&#225;neo &#40;oral&#41;Enfermedad injerto contra hu&#233;sped &#40;oral&#41;Pioderma gangrenoso &#40;oral&#41;&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">BaricitinibINCB-28050&#40;Olumiant&#174;&#44; Eli Lilly and Company&#47;Incyte&#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">JAK1JAK2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">C16H17N7O2S&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Oral&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Artritis reumatoide &#40;FDA 2018&#44; EMA 2017&#41;&#58; 4<span class="elsevierStyleHsp" style=""></span>mg una vez al d&#237;aDermatitis at&#243;pica moderada-grave &#40;EMA 2020&#41;&#58; 4<span class="elsevierStyleHsp" style=""></span>mg una vez 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">PsoriasisAlopecia areataDermatitis at&#243;picaLupus eritematoso sist&#233;mico&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">PeficitinibASP-015K&#40;Smyraf&#174;&#44; Astellas Pharma Inc&#46;&#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 &#40;selectividad para 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">C18H22N4O2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Oral&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Artritis reumatoide &#40;Jap&#243;n&#44; 2019&#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">Psoriasis&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">AbrocitinibPF-04965842&#40;Pfizer&#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">C14H21N5O2S&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Oral&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Ninguna&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">PsoriasisDermatitis at&#243;pica&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">UpadacitinibABT-494&#40;Rinvoq&#174;&#44; AbbVie&#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">C17H19F3N6O&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Oral&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Artritis reumatoide &#40;FDA y EMA 2019&#41;&#58; 15<span class="elsevierStyleHsp" style=""></span>mg una vez 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">Dermatitis at&#243;picaPsoriasis&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">DelgocitinibJTE-052&#40;Corectim&#174;&#44; Japan Tobacco&#47;LEO Pharma&#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">JAK1JAK2JAK3TYK2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">C16H18N6O&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">T&#243;pico&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Ninguna&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Dermatitis at&#243;picaAlopecia areata&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">BrepocitinibPF-06700841&#40;Pfizer&#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">TYK2JAK1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">C18H21F2N7O&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Oral&#47;t&#243;pico&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Ninguna&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Psoriasis &#40;oral&#44; t&#243;pico&#41;Alopecia areata &#40;oral&#41;Dermatitis at&#243;pica &#40;t&#243;pico&#41;Vit&#237;ligo &#40;oral&#41;&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">ATI-50002&#40;Aclaris Therapeutics&#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">JAK1JAK3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\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">T&#243;pico&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Ninguna&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Vit&#237;ligoAlopecia areataDermatitis at&#243;pica&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">RitlecitinibPF-06651600&#40;Pfizer&#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">JAK3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">C15H19N5O&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Oral&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Ninguna&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Vit&#237;ligoAlopecia areata&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">GusacitinibASN002&#40;Asana BioSciences&#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">JAK &#40;JAK1&#44; JAK2&#44; JAK3&#44; TYK2&#41;&#47;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">C24H28N802&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Oral&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Ninguna&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Dermatitis at&#243;pica&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">ItacitinibINCB-039110&#40;Incyte Corporation&#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">C26H23F4N9O&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Oral&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Ninguna&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">PsoriasisEnfermedad injerto contra hu&#233;sped&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">SolcitinibGSK-2586184&#40;GlaxoSmithKline&#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">C22H23N5O2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Oral&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Ninguna&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Psoriasis&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">FilgotinibG-146034&#40;Galapagos&#47;Gilead Sciences&#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">C21H23N5O3S&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Oral&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Ninguna&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Psoriasis&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">SHR0302&#40;Jiangsu Hengrui Medicine Co&#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">-&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Oral&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Ninguna&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Dermatitis at&#243;picaAlopecia areata&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">INCB054707&#40;Incyte Corporation&#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">-&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Oral&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Ninguna&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Hidradenitis supurativa&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">DeucravacitinibBMS-986165 &#40;Bristol-Myers Squibb&#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">TYK2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\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">Oral&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Ninguna&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Psoriasis&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">PF-06826647 &#40;Pfizer&#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">TYK2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\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">Oral&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
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