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Las formas moderadas-graves pueden representar entre 41 y 69&#37; de los pacientes con DA en Espa&#241;a&#44; sobre la base de diferentes criterios de gravedad<a class="elsevierStyleCrossRefs" href="#bib0190"><span class="elsevierStyleSup">5&#44;6</span></a>&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">La DA moderada-grave tiene un impacto econ&#243;mico importante&#44; que afecta a la calidad de vida y a la esfera psicosocial de los pacientes y sus familiares&#44; principalmente a causa del prurito&#44; que puede desencadenar cuestiones relacionadas con el sue&#241;o y trastornos psiqui&#225;tricos &#40;p&#46; ej&#46;&#44; ansiedad&#44; depresi&#243;n&#41;<a class="elsevierStyleCrossRefs" href="#bib0185"><span class="elsevierStyleSup">4&#8211;7</span></a>&#46; En los pacientes adultos&#44; la DA puede afectar tambi&#233;n a la productividad laboral<a class="elsevierStyleCrossRefs" href="#bib0170"><span class="elsevierStyleSup">1&#44;6</span></a>&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">El objetivo del tratamiento es reducir los s&#237;ntomas y el n&#250;mero de recidivas&#44; y controlar al mismo tiempo la enfermedad a largo plazo<a class="elsevierStyleCrossRefs" href="#bib0205"><span class="elsevierStyleSup">8&#8211;10</span></a>&#46; En el momento de realizar el estudio&#44; los tratamientos recomendados en las gu&#237;as para las formas moderadas-graves inclu&#237;an corticosteroides t&#243;picos e inhibidores de la calcineurina&#44; fototerapia&#44; corticosteroides orales a corto plazo&#44; inmunosupresores convencionales &#40;ciclosporina&#44; micofenolato de mofetilo&#44; azatioprina y metotrexato&#44; no estando indicados los tres &#250;ltimos para DA&#41;&#44; y el anticuerpo monoclonal dupilumab<a class="elsevierStyleCrossRefs" href="#bib0170"><span class="elsevierStyleSup">1&#44;11&#44;12</span></a>&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">Aunque diversos estudios recientes han descrito la carga de la enfermedad en Espa&#241;a<a class="elsevierStyleCrossRefs" href="#bib0230"><span class="elsevierStyleSup">13&#44;14</span></a>&#44; existe evidencia limitada sobre el uso de los tratamientos a lo largo del tiempo y el impacto econ&#243;mico de la enfermedad en condiciones de pr&#225;ctica cl&#237;nica habitual&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">Este estudio describi&#243; las caracter&#237;sticas sociodemogr&#225;ficas y cl&#237;nicas&#44; los patrones terap&#233;uticos&#44; el URS y los costes en adultos con DA que iniciaron tratamiento con f&#225;rmacos sist&#233;micos o fototerapia en el &#225;mbito del mundo real en Espa&#241;a&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Pacientes y m&#233;todos</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Dise&#241;o del estudio</span><p id="par0030" class="elsevierStylePara elsevierViewall">Estudio longitudinal&#44; retrospectivo y no intervencionista basado en las historias cl&#237;nicas electr&#243;nicas incluidas en la base de datos Big-Pac en Espa&#241;a&#44; que fue realizado para describir las caracter&#237;sticas sociodemogr&#225;ficas&#47;cl&#237;nicas&#44; patrones de tratamiento&#44; URS y costes asociados&#46; Se incluy&#243; en el mismo a los pacientes adultos con DA que hab&#237;an iniciado recientemente un tratamiento con f&#225;rmacos sist&#233;micos &#40;inmunosupresores orales&#44; corticosteroides sist&#233;micos&#44; o f&#225;rmacos biol&#243;gicos&#41; o fototerapia entre el 01&#47;01&#47;2012 y el 31&#47;12&#47;2016 &#40;es decir&#44; periodo de inclusi&#243;n&#59; <a class="elsevierStyleCrossRef" href="#fig0005">fig&#46; 1</a>&#41;&#46; Se realiz&#243; seguimiento a los pacientes durante tres a&#241;os&#44; desde la fecha de inicio del primer tratamiento sist&#233;mico o fototerapia &#40;es decir&#44; fecha &#237;ndice&#41;&#44; hasta el 31&#47;12&#47;2019&#46; Se utiliz&#243; un periodo pre-&#237;ndice de dos a&#241;os para verificar que no se hab&#237;an documentado previamente registros de f&#225;rmacos sist&#233;micos o fototerapia&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0155" class="elsevierStylePara elsevierViewall">Se respet&#243; la confidencialidad de los datos &#40;an&#243;nimos y disociados&#41; en cumplimiento de la Ley Org&#225;nica 3&#47;2018&#44; de 5 de diciembre sobre Protecci&#243;n de datos personales y garant&#237;a de derechos &#40;<a href="https://www.boe.es/eli/es/lo/2018/12/05/3">https&#58;&#47;&#47;www&#46;boe&#46;es&#47;eli&#47;es&#47;lo&#47;2018&#47;12&#47;05&#47;3</a>&#41;&#46; El estudio fue aprobado por el Comit&#233; de &#201;tica del Consorci Sanitari de Terrassa &#40;Barcelona&#44; Espa&#241;a&#41;&#44; y fue realizado conforme a los principios &#233;ticos de la Declaraci&#243;n de Helsinki y la legislaci&#243;n aplicable en Espa&#241;a&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Fuente de los datos</span><p id="par0035" class="elsevierStylePara elsevierViewall">Los datos se obtuvieron de la base de datos Big-Pac &#40;<span class="elsevierStyleItalic">Atrys Health-Real Life Data</span>&#44; Madrid&#44; Espa&#241;a&#41;&#44; que recopila historias cl&#237;nicas electr&#243;nicas anonimizadas de atenci&#243;n primaria y secundaria&#44; registros de dispensaci&#243;n de f&#225;rmacos y otras bases de datos complementarias de siete regiones espa&#241;olas&#46; La poblaci&#243;n asignada a los centros de salud de los que se extrajeron los datos inclu&#237;a a 1&#46;867&#46;108 habitantes en el momento de la extracci&#243;n&#44; pudiendo considerarse representativos de la poblaci&#243;n espa&#241;ola<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">15</span></a>&#46; La base de datos est&#225; registrada en <span class="elsevierStyleItalic">European Network of Centers for Pharmacoepidemiology and Pharmacovigilance</span> &#40;ENCePP&#174;&#41; &#40;<a href="http://www.encepp.eu/encepp/viewResource.htm?id=29236">http&#58;&#47;&#47;www&#46;encepp&#46;eu&#47;encepp&#47;viewResource&#46;htm&#63;id&#61;29236&#35;</a>&#41;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Poblaci&#243;n de estudio</span><p id="par0040" class="elsevierStylePara elsevierViewall">Se incluy&#243; a los pacientes que cumplieron los criterios de inclusi&#243;n siguientes en la fecha &#237;ndice&#58; a&#41; con registro de diagn&#243;stico de DA previo a la fecha &#237;ndice&#44; de acuerdo con los c&#243;digos <span class="elsevierStyleItalic">International Classification of Diseases&#44; Ninth Revision&#44; Clinical Modification</span> &#40;ICD-9-CM&#41; &#40;691&#46;8 &#8211; otras DA y estados relacionados&#44; o 692&#46;9 &#8211; dermatitis de contacto y otros eccemas&#44; causa inespec&#237;fica&#44; incluyendo &#171;al&#233;rgico&#187; o &#171;at&#243;pico&#187; en el campo de diagn&#243;stico &#171;descripci&#243;n&#187; de la base de datos&#41;&#44; b&#41; iniciaron tratamiento con fototerapia o f&#225;rmacos sist&#233;micos entre el 01&#47;01&#47;2012 y el 31&#47;12&#47;2016&#44; c&#41; edad de al menos 18 a&#241;os&#44; d&#41; paciente incluido en el programa de prescripciones para la obtenci&#243;n de las recetas m&#233;dicas &#40;con registro constatado de la dosis diaria&#44; el intervalo de tiempo y la duraci&#243;n de cada tratamiento administrado&#59; dos o m&#225;s recetas durante el periodo de seguimiento&#41;&#59; e&#41; con dos o m&#225;s registros sanitarios&#44; f&#41; continuamente registrados en la base de datos durante al menos tres a&#241;os desde la fecha &#237;ndice&#46; Se excluy&#243; a los pacientes cuando&#58; a&#41; hab&#237;an sido derivados a otros centros&#44; estaban desplazados o fuera del &#225;rea&#44; b&#41; estaban permanentemente institucionalizados&#44; c&#41; ten&#237;an una enfermedad terminal o d&#41; ten&#237;an antecedentes de fototerapia o medicaci&#243;n sist&#233;mica en el periodo de dos a&#241;os previo a la fecha &#237;ndice&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">Solo se incluy&#243; en el an&#225;lisis a los pacientes con c&#243;digo ICD-9-CM relacionado con DA documentado durante al menos una prescripci&#243;n de tratamiento sist&#233;mico durante el periodo de inclusi&#243;n&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Criterios de valoraci&#243;n y variables del estudio</span><p id="par0050" class="elsevierStylePara elsevierViewall">Se obtuvieron los datos sociodemogr&#225;ficos y cl&#237;nicos en la fecha &#237;ndice&#44; o previamente a la misma&#44; incluyendo edad&#44; sexo&#44; IMC&#44; tiempo desde el diagn&#243;stico de DA&#44; edad al iniciarse la DA&#46; Se describieron las comorbilidades cl&#237;nicamente relevantes m&#225;s frecuentes &#40;frecuencia<span class="elsevierStyleHsp" style=""></span>&#8805;<span class="elsevierStyleHsp" style=""></span>5&#37;&#41; sobre la base de los c&#243;digos ICD-9-CM &#40;<a class="elsevierStyleCrossRef" href="#sec0085">Material Suplementario Tabla 1</a>&#41;&#46; Se calcularon el n&#250;mero medio &#40;DE&#41; de comorbilidades por paciente&#46; Se extrajeron los tratamientos t&#243;picos para DA en los seis meses previos a la fecha &#237;ndice&#44; as&#237; como los tratamientos concomitantes seleccionados &#40;<a class="elsevierStyleCrossRef" href="#sec0085">Material Suplementario Tabla 2</a>&#59; c&#243;digos ATC<a class="elsevierStyleCrossRef" href="#bib0245"><span class="elsevierStyleSup">16</span></a>&#41;&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">Se obtuvieron los tratamientos sist&#233;micos y la fototerapia en la fecha &#237;ndice y a lo largo del periodo de seguimiento&#46; Se construyeron l&#237;neas de tratamiento &#40;L&#237;nea 1&#44; L&#237;nea 2&#44; L&#237;nea 3 o L&#237;nea &#62; 3&#41;&#46; Se registraron el&#40;los&#41; primer&#40;os&#41; tratamiento&#40;s&#41; o fototerapia&#40;s&#41; iniciado&#40;s&#41; dentro del periodo de inclusi&#243;n &#40;tratamiento &#237;ndice o terapia de primera l&#237;nea&#41; prescritos en monoterapia o combinaci&#243;n &#40;cuando se prescrib&#237;a m&#225;s de un f&#225;rmaco el mismo d&#237;a&#41;&#46; Para las l&#237;neas de tratamiento subsiguientes se defini&#243; la combinaci&#243;n como el uso concomitante de dos o m&#225;s f&#225;rmacos sist&#233;micos o fototerapia&#46; Los cambios del tratamiento &#237;ndice o las l&#237;neas de tratamiento subsiguientes incluyen&#58; a&#41; discontinuaci&#243;n&#58; fin del tratamiento sist&#233;mico o fototerapia con la existencia de un intervalo entre dispensaciones sucesivas<span class="elsevierStyleHsp" style=""></span>&#8805;<span class="elsevierStyleHsp" style=""></span>60 d&#237;as de duraci&#243;n&#44; b&#41; cambio&#58; fin del tratamiento sist&#233;mico o fototerapia con inicio de un nuevo tratamiento sist&#233;mico dentro del periodo de 60 d&#237;as siguiente al fin del tratamiento previo o c&#41; adici&#243;n&#58; inicio de un nuevo tratamiento sist&#233;mico o fototerapia mientras se sigue prescribiendo el tratamiento previo&#46; La duraci&#243;n del tratamiento para un f&#225;rmaco espec&#237;fico se determin&#243; como el tiempo &#40;d&#237;as&#41; desde el inicio de dicho f&#225;rmaco a la fecha de discontinuaci&#243;n o cambio&#46; El tratamiento sist&#233;mico continuo durante el seguimiento de tres a&#241;os se defini&#243; como la falta de discontinuaci&#243;n del tratamiento sist&#233;mico &#40;excluyendo corticosteroides orales&#41; dentro de dicho periodo de tiempo<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">17</span></a>&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall">El URS se describi&#243; sobre la base de los recursos registrados durante el periodo de seguimiento de tres a&#241;os&#44; utiliz&#225;ndose para calcular los costes sanitarios asociados &#40;consultas m&#233;dicas&#44; d&#237;as de hospitalizaci&#243;n&#44; visitas a urgencias&#44; solicitudes de diagn&#243;stico o terapia&#44; prescripci&#243;n de f&#225;rmacos&#41; y los costes no sanitarios &#40;es decir&#44; d&#237;as de baja&#41;&#46; Solo se consider&#243; para el an&#225;lisis el URS asociado a los c&#243;digos ICD-9-CM dermatol&#243;gicos&#44; exceptuando los d&#237;as de baja&#44; ya que no tienen c&#243;digo ICD-9-CM vinculado&#46; Los costes se expresaron como coste medio por paciente &#40;media&#47;unidad&#41; por a&#241;o&#44; as&#237; como el coste total en el periodo de seguimiento de tres a&#241;os&#46; Los costes unitarios se detallan en el <a class="elsevierStyleCrossRef" href="#sec0085">Material Suplementario Tabla 3</a> &#40;a&#241;o 2019&#41;&#46; Las tarifas se obtuvieron de la contabilidad anal&#237;tica&#44; exceptuando lo referente a medicaci&#243;n y d&#237;as de baja&#46; Las prescripciones m&#233;dicas se cuantificaron conforme al precio de venta al p&#250;blico por envase en el momento de la prescripci&#243;n<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">18</span></a>&#46; Los d&#237;as de baja se consideraron en virtud del salario medio interprofesional<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">19</span></a>&#46; Este estudio no consider&#243; los costes directos no sanitarios pagados por el paciente&#47;familiar&#44; ya que no est&#225;n registrados en la base de datos&#46;</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">An&#225;lisis estad&#237;sticos</span><p id="par0065" class="elsevierStylePara elsevierViewall">Los datos fueron analizados descriptivamente&#46; Para las variables categ&#243;ricas se aportaron las frecuencias absolutas y relativas&#46; Las variables continuas fueron reportadas utilizando medias&#44; desviaci&#243;n est&#225;ndar &#40;DE&#41;&#44; mediana&#44; y percentiles 25&#176; y 75&#176; de la distribuci&#243;n &#40;rango intercuart&#237;lico&#41;&#46; Los resultados se presentaron de manera global y por tratamiento &#237;ndice&#46; Cuando faltaron datos&#44; se aport&#243; el n&#250;mero de valores ausentes&#46; Se utiliz&#243; el programa SPSSWIN&#44; versi&#243;n 23 para el an&#225;lisis&#46;</p></span></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Resultados</span><p id="par0070" class="elsevierStylePara elsevierViewall">De los 1&#46;867&#46;108 pacientes incluidos en la base de datos Big-Pac&#44; se incluyeron 1&#46;995 en el an&#225;lisis &#40;<a class="elsevierStyleCrossRef" href="#sec0085">Supl&#46; fig&#46; 1</a>&#41;&#46;</p><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Caracter&#237;sticas sociodemogr&#225;ficas y cl&#237;nicas</span><p id="par0075" class="elsevierStylePara elsevierViewall">La edad media &#40;DE&#41; en la fecha de &#237;ndice fue de 59&#44;8 &#40;17&#44;3&#41; a&#241;os&#44; siendo mujeres 64&#44;4&#37; de los pacientes &#40;n &#61; 1&#46;285&#41;&#46; Entre los pacientes de los que se dispon&#237;a de datos &#40;n &#61; 1&#46;189&#41;&#44; el IMC medio &#40;DE&#41; fue de 29&#44;5 &#40;6&#41; kg&#47;m<span class="elsevierStyleSup">2</span>&#46; El tiempo medio &#40;DE&#41; desde el diagn&#243;stico de DA fue de 23&#44;2 &#40;13&#44;4&#41; a&#241;os&#44; correspondiendo 84&#37; al inicio de la DA en adultos&#46; Las principales comorbilidades fueron ansiedad general &#40;37&#44;9&#37;&#41;&#44; hipertensi&#243;n arterial &#40;35&#44;9&#37;&#41; y dislipidemia &#40;35&#44;3&#37;&#41; &#40;<a class="elsevierStyleCrossRef" href="#fig0010">fig&#46; 2</a>&#41;&#46; Los antibi&#243;ticos&#44; antihistam&#237;nicos y antidepresivos estuvieron presentes en 46&#44;8&#37;&#44; 29&#44;9&#37; y 26&#44;7&#37; de los pacientes en la fecha &#237;ndice&#44; respectivamente &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">tabla 1</a>&#41;&#46;</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><elsevierMultimedia ident="tbl0005"></elsevierMultimedia></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Patrones de tratamiento</span><p id="par0080" class="elsevierStylePara elsevierViewall">Los primeros tratamientos sist&#233;micos o fototerapia que iniciaron los pacientes en la fecha &#237;ndice &#40;es decir&#44; L&#237;nea 1&#41; fueron &#40;<a class="elsevierStyleCrossRef" href="#fig0015">fig&#46; 3</a>&#41;&#58; corticosteroides orales &#40;83&#44;6&#37;&#59; n &#61; 1&#46;668&#41;&#44; inmunosupresores &#40;12&#44;8&#37;&#59; n &#61; 256 principalmente ciclosporina &#91;5&#44;3&#37;&#93; y metotrexato &#91;3&#44;9&#37;&#93;&#41;&#44; f&#225;rmacos biol&#243;gicos &#40;0&#44;8&#37;&#59; n &#61; 15&#41;&#44; otros f&#225;rmacos sist&#233;micos &#40;4&#44;3&#37;&#59; n &#61; 86&#41; y fototerapia &#40;0&#44;2&#37;&#59; n &#61; 3&#41;&#46; La mayor&#237;a de los pacientes recibieron estos primeros tratamientos sist&#233;micos como monoterapia &#40;98&#44;4 vs&#46; 1&#44;7&#37; en combinaci&#243;n&#44; siendo los corticosteroides orales la principal terapia en combinaci&#243;n&#41;&#46; La mediana de la duraci&#243;n &#40;RIC&#41; de las terapias de primera l&#237;nea se presenta en la <a class="elsevierStyleCrossRef" href="#tbl0010">tabla 2</a>&#46;</p><elsevierMultimedia ident="fig0015"></elsevierMultimedia><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0085" class="elsevierStylePara elsevierViewall">Del n&#250;mero total de pacientes incluidos en el estudio &#40;n &#61; 1&#46;995&#41;&#44; 50&#44;7&#37; &#40;n &#61; 1&#46;011&#41;&#44; 11&#44;7&#37; &#40;n &#61; 233&#41; y 3&#44;5&#37; &#40;n &#61; 70&#41; requirieron una segunda&#44; tercera o cuarta l&#237;nea de tratamiento sist&#233;mico&#44; respectivamente &#40;<a class="elsevierStyleCrossRef" href="#fig0020">fig&#46; 4</a>&#41;&#46; El n&#250;mero medio &#40;DE&#41; de l&#237;neas de tratamiento sist&#233;mico o fototerapia fue de 1&#44;7 &#40;0&#44;8&#41;&#46; Como se muestra en la <a class="elsevierStyleCrossRef" href="#tbl0015">tabla 3</a>&#44; el uso de corticosteroides orales fue alto en todas las l&#237;neas de tratamiento &#40;83&#44;6&#37; en la L&#237;nea 1&#44; 86&#44;8&#37; en la L&#237;nea 2&#44; 74&#44;7&#37; en la L&#237;nea 3 y 84&#44;3&#37; en las L&#237;neas &#62; 3&#41;&#44; mientras que los inmunosupresores fueron m&#225;s frecuentemente utilizados en l&#237;neas posteriores &#40;12&#44;8&#37; en la L&#237;nea 1&#44; 14&#44;5&#37; en la L&#237;nea 2&#44; 38&#44;6&#37; en la L&#237;nea 3&#44; y 30&#37; en la L&#237;neas &#62; 3&#41;&#46; Los f&#225;rmacos biol&#243;gicos fueron m&#225;s frecuentemente utilizados en la L&#237;neas 2 &#40;11&#44;4&#37;&#41; y 3 &#40;13&#44;3&#37;&#41;&#46; El porcentaje de pacientes que recibieron fototerapia fue de 11&#44;2&#37;&#46; Durante el periodo de seguimiento de tres a&#241;os&#44; 12&#44;6&#37; &#40;n &#61; 252&#41; de los pacientes recibi&#243; tratamiento sist&#233;mico de manera continua &#40;<a class="elsevierStyleCrossRef" href="#tbl0020">tabla 4</a>&#41;&#46; Las trayectorias terap&#233;uticas fueron heterog&#233;neas &#40;<a class="elsevierStyleCrossRef" href="#fig0025">fig&#46; 5</a>&#41;&#46;</p><elsevierMultimedia ident="fig0020"></elsevierMultimedia><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><elsevierMultimedia ident="tbl0020"></elsevierMultimedia><elsevierMultimedia ident="fig0025"></elsevierMultimedia></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Uso de recursos sanitarios y costes asociados</span><p id="par0090" class="elsevierStylePara elsevierViewall">El coste anual medio &#40;DE&#41; por paciente fue de 1&#46;278&#8364; &#40;2&#46;079&#8364;&#41;&#44; con los componentes de costes siguientes &#40;<a class="elsevierStyleCrossRef" href="#fig0030">fig&#46; 6</a>&#41;&#58; 470&#8364; &#40;36&#44;8&#37;&#41; bajas por enfermedad&#44; 200&#8364; &#40;15&#44;7&#37;&#41; consultas al especialista&#44; 187&#8364; &#40;14&#44;7&#37;&#41; hospitalizaci&#243;n&#44; 167&#8364; &#40;13&#44;1&#37;&#41; medicaci&#243;n&#44; 128&#8364; &#40;10&#37;&#41; consultas de atenci&#243;n primaria&#44; 83&#8364; &#40;6&#44;5&#37;&#41; solicitudes de pruebas diagn&#243;sticas&#44; y 42&#8364; &#40;3&#44;3&#37;&#41; visitas a urgencias&#46;</p><elsevierMultimedia ident="fig0030"></elsevierMultimedia><p id="par0095" class="elsevierStylePara elsevierViewall">El coste total por paciente en los tres a&#241;os de seguimiento fue de 3&#46;835&#8364; &#40;6&#46;238&#8364;&#41; &#40;<a class="elsevierStyleCrossRef" href="#tbl0025">tabla 5</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0025"></elsevierMultimedia></span></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Discusi&#243;n</span><p id="par0100" class="elsevierStylePara elsevierViewall">El estudio Derma-Atopic caracteriz&#243; la carga cl&#237;nica&#44; terap&#233;utica y econ&#243;mica de la DA en una poblaci&#243;n adulta del mundo real tratada con f&#225;rmacos sist&#233;micos en Espa&#241;a&#46; Dicho estudio aporta una perspectiva sobre el patr&#243;n de uso de los tratamientos sist&#233;micos durante un periodo de tres a&#241;os en Espa&#241;a&#46;</p><p id="par0105" class="elsevierStylePara elsevierViewall">Los pacientes con DA incluidos en el estudio fueron predominantemente mujeres&#44; diagnosticados en la en la edad adulta&#44; con una media de 60 a&#241;os en el momento de iniciarse el tratamiento sist&#233;mico&#44; duraci&#243;n de la enfermedad prolongada y alta carga de comorbilidades &#40;ej&#46;&#58; ansiedad&#44; enfermedades cardiovasculares&#41;&#46; Se encontr&#243; que la edad de inicio del tratamiento sist&#233;mico era consistente con otros estudios&#44; basados en bases de datos sanitarias que inclu&#237;an pacientes de atenci&#243;n primaria y secundaria en Espa&#241;a<a class="elsevierStyleCrossRefs" href="#bib0195"><span class="elsevierStyleSup">6&#44;13</span></a>&#44; y fuera de Espa&#241;a<a class="elsevierStyleCrossRef" href="#bib0265"><span class="elsevierStyleSup">20</span></a>&#46; Por el contrario&#44; los pacientes seleccionados para participar en los estudios de recopilaci&#243;n de datos de atenci&#243;n primaria<a class="elsevierStyleCrossRefs" href="#bib0270"><span class="elsevierStyleSup">21&#44;22</span></a>&#44; donde se aplicaron criterios de selecci&#243;n de edad m&#225;s estrictos &#40;p&#46; ej&#46;&#44; adultos de 18 a 65 a&#241;os&#41;&#44; presentaron edades medias m&#225;s bajas&#46; Las comorbilidades coexistentes relacionadas con la DA&#44; tales como asma y rinitis al&#233;rgica &#40;&#8216;marcha at&#243;pica&#8217;&#41;&#44; estuvieron presentes aproximadamente en el 16&#37; de los pacientes del estudio actual&#46; Esta frecuencia fue inferior a la reportada por Bruin Weller et al&#46; <span class="elsevierStyleSup">21</span> en 2020&#44; donde cerca de un tercio de los pacientes con enfermedad moderada&#8211;grave padec&#237;an tambi&#233;n asma&#46; Los tratamientos concomitantes que incluyen antibi&#243;ticos&#44; antihistam&#237;nicos y antidepresivos&#44; estuvieron altamente presentes en la poblaci&#243;n de estudio&#44; lo cual subraya la carga significativa de los s&#237;ntomas de la DA &#40;p&#46; ej&#46;&#44; prurito&#41; y de las comorbilidades&#46;</p><p id="par0110" class="elsevierStylePara elsevierViewall">Los pacientes analizados en el estudio presentaron un uso considerable de tratamientos sist&#233;micos&#44; y m&#225;s del 50&#37; de ellos requiri&#243; al menos dos l&#237;neas de tratamiento en el periodo de tres a&#241;os del estudio&#46; La primera l&#237;nea de tratamiento se bas&#243; principalmente en cursos cortos de corticosteroides orales&#44; los cuales estuvieron consistentemente presentes en todas las l&#237;neas de tratamiento &#40;tanto en monoterapia como en combinaci&#243;n&#41;&#46; El elevado uso de corticosteroides orales&#44; frente a otras alternativas tales como inmunosupresores&#44; podr&#237;a explicarse por la contribuci&#243;n de los pacientes de atenci&#243;n primaria&#44; adem&#225;s de los de atenci&#243;n secundaria&#44; donde se esperar&#237;a un mayor uso de inmunosupresores&#46; Los pacientes que recibieron inmunosupresores o f&#225;rmacos biol&#243;gicos como primera l&#237;nea&#44; siguieron en tratamiento durante periodos m&#225;s prolongados &#40;media de 117 y 331 d&#237;as&#44; respectivamente&#41;&#46; El uso de inmunosupresores &#40;principalmente ciclosporina y metotrexato&#44; este &#250;ltimo utilizado fuera de indicaci&#243;n&#41; aument&#243; a medida que los pacientes avanzaban en el algoritmo de tratamiento&#44; de acuerdo con las recomendaciones de las gu&#237;as de tratamiento actuales<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">1</span></a>&#46; Resulta interesante que&#44; aunque las directrices limitan el uso de inmunoglobulina intravenosa en los ni&#241;os con enfermedad refractaria&#44; cerca de 4&#37; de los pacientes del estudio&#44; y 20 de los 240 pacientes incluidos en el estudio realizado por Pereyra-Rodriguez et al&#46;<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">12</span></a>&#44; reportaron el uso de este tratamiento en adultos&#46; Como este estudio aporta una visi&#243;n general sobre el escenario del tratamiento de la DA entre 2013 y 2019&#44; el uso de dupilumab &#40;financiado en Espa&#241;a desde 2020&#41;<a class="elsevierStyleCrossRef" href="#bib0280"><span class="elsevierStyleSup">23</span></a> y de otros f&#225;rmacos biol&#243;gicos &#40;fuera de indicaci&#243;n&#41; fue escaso&#46; Se espera que la disponibilidad de f&#225;rmacos biol&#243;gicos y de los inhibidores de la quinasa Janus &#40;JAK&#41; d&#233; lugar a un cambio en el paradigma de tratamiento de la DA moderada-grave<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">24</span></a>&#44; lo que requerir&#225; una mayor caracterizaci&#243;n de las v&#237;as terap&#233;uticas en los a&#241;os futuros&#46;</p><p id="par0115" class="elsevierStylePara elsevierViewall">La variabilidad de la pr&#225;ctica cl&#237;nica y las trayectorias terap&#233;uticas observados en el estudio confirma la naturaleza heterog&#233;nea de la enfermedad&#44; que requiere estrategias terap&#233;uticas individualizadas en la pr&#225;ctica rutinaria<a class="elsevierStyleCrossRefs" href="#bib0230"><span class="elsevierStyleSup">13&#44;25&#44;26</span></a>&#46; Cerca de 20&#37; de los pacientes del estudio recibieron tratamientos sist&#233;micos de manera continua a lo largo de un a&#241;o&#44; y un 13&#37; durante el periodo de tres a&#241;os&#46; Estos hallazgos sugieren que&#44; a pesar de que algunos pacientes puedan presentar la enfermedad a causa de un brote agudo que requiera intervenciones farmacol&#243;gicas a corto plazo para el alivio de los s&#237;ntomas&#44; otros desarrollan un curso cr&#243;nico de la enfermedad con lesiones cut&#225;neas persistentes y prurito intenso<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">27</span></a>&#46; Sin embargo&#44; la falta de datos sobre las puntuaciones de gravedad&#44; los resultados reportados por el paciente &#40;PRO&#44; del ingl&#233;s patient reported outcomes&#41; y los s&#237;ntomas&#44; limitaron la interpretaci&#243;n de estos resultados&#46; Adem&#225;s&#44; es necesaria la investigaci&#243;n futura que describa el tipo de facultativos que inician y prescriben tratamientos sist&#233;micos &#40;p&#46; ej&#46;&#44; m&#233;dico general frente a dermat&#243;logo&#41; y los patrones de derivaci&#243;n para los pacientes de DA moderada&#8211;grave en el mundo real&#46;</p><p id="par0120" class="elsevierStylePara elsevierViewall">La DA supone una carga econ&#243;mica significativa para el sistema sanitario&#44; los pacientes y sus familiares&#44; especialmente en sus formas m&#225;s graves<a class="elsevierStyleCrossRefs" href="#bib0170"><span class="elsevierStyleSup">1&#44;2&#44;28</span></a>&#46; El presente estudio estim&#243; un coste de la DA moderada&#8211;grave en adultos de 1&#46;278&#8364; por paciente y a&#241;o &#40;costes sanitarios&#58; 63&#37;&#59; costes indirectos&#58; 37&#37;&#41;&#46; Un estudio reciente realizado en Catalu&#241;a report&#243; un elevado coste unitario&#44; que ascendi&#243; a 3&#46;397&#8364; para los pacientes con enfermedad grave&#44; y 2&#46;111&#8364; para los pacientes con enfermedad moderada&#44; correspondiendo 75&#44;5&#37; a los costes sanitarios&#44; y 24&#44;5&#37; a los costes indirectos<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">6</span></a>&#46; En ambos estudios los costes indirectos basados en p&#233;rdidas de productividad estuvieron altamente representados&#44; hallazgo que coincide con la evidencia existente&#44; que sugiere un impacto significativo de la DA en la productividad laboral<a class="elsevierStyleCrossRef" href="#bib0310"><span class="elsevierStyleSup">29</span></a>&#46;</p><p id="par0125" class="elsevierStylePara elsevierViewall">Este estudio presenta ciertas limitaciones&#46; La posible imprecisi&#243;n de la codificaci&#243;n diagn&#243;stica para la DA y otras comorbilidades&#44; o la falta de informaci&#243;n en la base de datos sobre el nivel socioecon&#243;mico y el estatus cl&#237;nico&#44; las regiones y hospitales participantes &#40;que son confidenciales&#41;&#44; la adherencia terap&#233;utica&#44; los fenotipos etc&#46;&#44; pueden ser limitaciones potenciales para el estudio&#46; De igual modo&#44; puede existir una sobrerrepresentaci&#243;n de casos de pacientes de mayor edad con DA&#44; lo cual puede limitar la comparaci&#243;n con los estudios que utilizan diferentes fuentes de datos&#46; La validaci&#243;n y representatividad de la base de datos BIG-PAC ha sido previamente explorada&#44; aunque el an&#225;lisis careci&#243; del nivel socioecon&#243;mico y educativo&#44; y del tipo de poblaci&#243;n cubierta &#40;urbana&#47;rural&#41;<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">15</span></a>&#46; Aunque persiste cierta incertidumbre sobre si los resultados obtenidos en el presente estudio podr&#237;an generalizarse a la poblaci&#243;n general de Espa&#241;a&#44; la evidencia publicada utilizando la base de datos BIG-PAC indica que es adecuada para realizar estudios en el &#225;mbito del mundo real para diversas situaciones&#44; incluyendo la DA en Espa&#241;a<a class="elsevierStyleCrossRefs" href="#bib0230"><span class="elsevierStyleSup">13&#44;30&#8211;33</span></a>&#46; Por otro lado&#44; la base de datos BIG-PAC est&#225; registrada en el inventario ENCePP como fuente de datos elegible para la realizaci&#243;n de estudios sobre farmacoepidemiolog&#237;a y farmacovigilancia en Europa&#46; El tratamiento y los PRO&#44; as&#237; como la incidencia de brotes no fueron registrados&#44; lo cual dificulta la interpretaci&#243;n cl&#237;nica de los resultados&#46; El estudio intent&#243; seleccionar pacientes que iniciaban terapia de f&#225;rmacos sist&#233;micos o fototerapia por primera vez para tratar la DA en la vida adulta&#46; Por este motivo&#44; los pacientes con historia previa de uso de f&#225;rmacos sist&#233;micos o fototerapia en los dos a&#241;os anteriores a la fecha &#237;ndice fueron excluidos&#46; Sin embargo&#44; no se puede descartar el uso previo de f&#225;rmacos sist&#233;micos m&#225;s all&#225; de dichos dos a&#241;os&#46; Adem&#225;s&#44; los costes se basaron en la identificaci&#243;n de recursos asociados a la DA&#44; una aproximaci&#243;n necesaria en ausencia de los c&#243;digos reales vinculados a cada recurso&#46; Por tanto&#44; es posible que se hayan sobreestimado algunos tipos de recursos&#46;</p></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Conclusiones</span><p id="par0130" class="elsevierStylePara elsevierViewall">Este estudio describi&#243; una poblaci&#243;n de adultos del mundo real con DA&#44; tratados con f&#225;rmacos sist&#233;micos en Espa&#241;a&#46; Los resultados sugieren una alta comorbilidad y carga econ&#243;mica para el sistema sanitario&#44; los pacientes y sus familiares&#46; A pesar de observarse variabilidad en los patrones de tratamiento&#44; los cursos cortos de corticosteroides orales siguieron siendo la principal opci&#243;n de tratamiento&#44; seguida de los inmunosupresores&#44; utiliz&#225;ndose algunos de ellos fuera de indicaci&#243;n&#46; Esto subraya la necesidad de nuevos tratamientos sist&#233;micos indicados para la DA&#46;</p></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0130">Financiaci&#243;n</span><p id="par0135" class="elsevierStylePara elsevierViewall">Este estudio fue financiado mediante <span class="elsevierStyleGrantSponsor" id="gs1">Eli Lilly and Company</span>&#46;</p></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0135">Conflicto de intereses</span><p id="par0140" class="elsevierStylePara elsevierViewall">Esther Serra ha recibido honorarios por haber actuado de asesora cient&#237;fica y conferenciante para Eli Lilly and Company&#46; Esther Artime&#44; Silvia D&#237;az y Teresa Huete son empleadas y accionistas minoritarias de Eli Lilly and Company&#46; Ignacio Hern&#225;ndez&#44; Laura Lledo y Antoni Sicras son empleados y accionistas minoritarios de Atrys Health S&#46;A&#46; en Espa&#241;a&#46;</p></span></span>"
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        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Antecedentes</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">La dermatitis at&#243;pica &#40;DA&#41; moderada-grave tiene un impacto significativo en la vida de los pacientes&#44; muchos de los cuales requieren tratamiento sist&#233;mico para controlar los s&#237;ntomas &#40;p&#46; ej&#46;&#44; prurito&#41;&#46; Algunos tratamientos son usados fuera de indicaci&#243;n&#46; Este estudio describi&#243; caracter&#237;sticas sociodemogr&#225;ficas y cl&#237;nicas&#44; patrones de tratamiento&#44; uso de recursos sanitarios &#40;URS&#41; y costes asociados en adultos con DA que iniciaron tratamiento sist&#233;mico o fototerapia en la pr&#225;ctica habitual&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">M&#233;todos</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Este estudio observacional retrospectivo de historias cl&#237;nicas electr&#243;nicas en la base de datos BIG-PAC identific&#243; adultos con diagn&#243;stico previo de DA &#40;CIE-9&#58; 691&#46;8 o 692&#46;9&#41; que comenzaron con corticosteroides orales&#44; inmunosupresores&#44; biol&#243;gicos o fototerapia entre el 01&#47;01&#47;2012 y el 31&#47;12&#47;2016&#46; Se sigui&#243; a los pacientes durante tres a&#241;os desde el inicio del tratamiento&#44; hasta el 31&#47;12&#47;2019&#46; Los datos sobre las caracter&#237;sticas cl&#237;nicas de los pacientes&#44; patrones de tratamiento&#44; URS y costes se analizaron de forma descriptiva&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Resultados</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Los pacientes &#40;n &#61; 1995&#41; ten&#237;an una edad media de 60 a&#241;os&#44; 64&#37; eran mujeres&#44; con una media de 23 a&#241;os desde el diagn&#243;stico &#40;84&#37; ten&#237;an<span class="elsevierStyleHsp" style=""></span>&#8805;<span class="elsevierStyleHsp" style=""></span>18 a&#241;os al inicio de la DA&#41;&#46; Las principales comorbilidades fueron ansiedad &#40;38&#37;&#41;&#44; hipertensi&#243;n arterial &#40;36&#37;&#41; y dislipidemia &#40;35&#37;&#41;&#46; La mayor&#237;a de los pacientes utilizaron corticosteroides orales como primer tratamiento sist&#233;mico &#40;84&#37;&#59; duraci&#243;n media 29 d&#237;as&#41; e inmunosupresores en 13&#37; de los pacientes &#40;duraci&#243;n media 117 d&#237;as&#44; ciclosporina en 5&#37; y metotrexato en 4&#37;&#41;&#46; La mitad de los pacientes requirieron una segunda l&#237;nea de tratamiento sist&#233;mico y 12&#37; una tercera&#46; El uso de inmunosupresores y biol&#243;gicos aument&#243; simult&#225;neamente con las l&#237;neas de tratamiento&#46; Aproximadamente 13&#37; de los pacientes recibieron tratamientos sist&#233;micos de forma continua durante los tres a&#241;os de seguimiento&#46; El coste medio por paciente a tres a&#241;os fue de 3&#46;835 euros&#44; con un coste medio anual de 1&#46;278 euros&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusiones</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Los resultados sugieren una alta carga econ&#243;mica y de comorbilidad en esta poblaci&#243;n del mundo real de adultos con DA&#44; y la necesidad de nuevos tratamientos sist&#233;micos indicados para DA&#46;</p></span>"
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        "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Background</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Moderate&#8211;severe atopic dermatitis &#40;AD&#41; has a significant impact on patients&#8217; lives&#44; with many requiring systemic treatment to manage symptoms &#40;e&#46;g&#46;&#44; pruritus&#41;&#46; Several drugs are used off-label to treat AD&#46; This study describes sociodemographic&#47;clinical characteristics&#44; treatment patterns&#44; health resource use &#40;HRU&#41; and costs in adults with AD who initiated systemic treatment or phototherapy in routine practice&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Methods</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">This retrospective observational study of electronic medical records in the BIG-PAC database identified adults with prior diagnosis of AD &#40;ICD-9&#58; 691&#46;8 or 692&#46;9&#41; starting oral corticosteroids&#44; immunosuppressants&#44; biologics or phototherapy between 01&#47;01&#47;2012 and 31&#47;12&#47;2016&#46; Patients were followed for 3 years from treatment initiation&#44; up to 31&#47;12&#47;2019&#46; Data on patient characteristics&#44; treatment patterns&#44; HRU and costs were analyzed descriptively&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Results</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Patients &#40;<span class="elsevierStyleItalic">N</span> &#61; 1995&#41; had a mean age of 60 years&#44; 64&#37; were female&#44; with a mean time of 23 years since diagnosis &#40;84&#37; were<span class="elsevierStyleHsp" style=""></span> &#8805;<span class="elsevierStyleHsp" style=""></span>18 years at AD onset&#41;&#46; Main comorbidities were anxiety &#40;38&#37;&#41;&#44; arterial hypertension &#40;36&#37;&#41; and dyslipidemia &#40;35&#37;&#41;&#46; Most patients used oral corticosteroids as first systemic &#40;84&#37;&#59; median duration 29 days&#41; and immunosuppressants in 13&#37; of patients &#40;median duration 117 days&#44; 5&#37; cyclosporine and 4&#37; methotrexate&#41;&#46; Half of patients required a second line systemic and 12&#37; a third line&#46; The use of immunosuppressants and biologics increased with treatment lines&#46; About 13&#37; of patients received systemic treatments continuously over the 3-year follow-up&#46; The average 3-year per patient cost was 3835 euros&#44; with an average annual cost of 1278 euros&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusions</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Results suggest a high comorbidity and economic burden in this real-world adult population with AD&#44; and the need for systemic treatments indicated for use in AD&#46;</p></span>"
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Caracter&#237;sticas&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"><span class="elsevierStyleVsp" style="height:0.5px"></span></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
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                  \t\t\t\t"><span class="elsevierStyleItalic">Sexo&#44; &#37; mujeres</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">1&#46;285 &#40;64&#44;4&#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"><span class="elsevierStyleItalic">Tiempo desde el diagn&#243;stico de la DA &#40;media DE&#41;&#44; a&#241;os</span>&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">23&#44;2 &#40;13&#44;4&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Edad de inicio de la DA&#44; n &#40;&#37;&#41;</span>&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">8&#44;8 &#40;1&#44;3&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>&#60;14 a&#241;os&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>14&#8211;17 a&#241;os&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">177 &#40;8&#44;9&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>18&#8211;60 a&#241;os&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">1&#46;445 &#40;72&#44;4&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>&#62;60 a&#241;os&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">231 &#40;11&#44;6&#41;&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">29&#44;5 &#40;6&#41;<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>&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"><span class="elsevierStyleItalic">N&#250;mero de comorbilidades cr&#243;nicas por paciente&#44; media &#40;DE&#41;</span>&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">2&#44;5 &#40;1&#44;4&#41;&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  " align="" 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  " colspan="2" align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Tratamientos</span><span class="elsevierStyleItalic">no sist&#233;micos en los seis meses previos a la fecha &#237;ndice&#44;</span><span class="elsevierStyleItalic">n &#40;&#37;&#41;</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Corticosteroides t&#243;picos&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">629 &#40;31&#44;5&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Inmunomoduladores t&#243;picos&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">38 &#40;1&#44;9&#37;&#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"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
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                  \t\t\t\t  " colspan="2" align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Tratamientos concomitantes en la fecha &#237;ndice&#44; n &#40;&#37;&#41;</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Antihistam&#237;nicos&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">596 &#40;29&#44;9&#37;&#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
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Antibi&#243;ticos&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">933 &#40;46&#44;8&#37;&#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"><span class="elsevierStyleHsp" style=""></span>Antidepresivos&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">528 &#40;26&#44;7&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t" scope="col">Variable&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">N</span>&#61;1&#46;995</th></tr><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Mediana &#40;RIC&#41;&#44; d&#237;as&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Corticosteroides orales</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">1&#46;668&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">29 &#40;8&#44;8&#8211;53&#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"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Inmunosupresores</span>&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">256&nbsp;\t\t\t\t\t\t\n
                  \t\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">116&#44;5 &#40;49&#8211;286&#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
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Ciclosporina&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">106&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">86 &#40;33&#8211;236&#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
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Azatioprina&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">39&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">91 &#40;43&#8211;330&#44;5&#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"><span class="elsevierStyleHsp" style=""></span>Micofenolato de mofetilo&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">33&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">242 &#40;50&#8211;784&#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"><span class="elsevierStyleHsp" style=""></span>Metotrexato&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">78&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">133 &#40;83&#8211;387&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="3" align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">F&#225;rmacos biol&#243;gicos</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">15&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">331 &#40;277&#44;5&#8211;430&#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"><span class="elsevierStyleHsp" style=""></span>Dupilumab&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">327&#44;5 &#40;310&#44;8&#8211;344&#44;3&#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"><span class="elsevierStyleHsp" style=""></span>Omalizumab&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">368 &#40;299&#44;5&#8211;495&#44;5&#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"><span class="elsevierStyleHsp" style=""></span>Rituximab&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">331 &#40;201&#8211;431&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="3" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Otros f&#225;rmacos sist&#233;micos</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">86&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">30 &#40;30&#8211;30&#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"><span class="elsevierStyleHsp" style=""></span>Inmunoglobulinas&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">72&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">30 &#40;30&#8211;30&#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"><span class="elsevierStyleHsp" style=""></span>Interfer&#243;n gamma&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">12&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">165&#44;5 &#40;30&#8211;310&#44;5&#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"><span class="elsevierStyleHsp" style=""></span>Hidroxicloroquina&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">100 &#40;87&#8211;113&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Dupilumab&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">35 &#40;3&#44;5&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">Coste total por paciente&#44; media &#40;DE&#41;&nbsp;\t\t\t\t\t\t\n
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