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          "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Kaplan-Meier curve showing the survival of CsA in the management of AD&#44; and psoriasis&#46;</p>"
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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Atopic dermatitis &#40;AD&#41; is a chronic immune-mediated disease believed to affect 20&#37; and 8&#37; of the pediatric and adult populations&#44; respectively&#46;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">1</span></a> Moderate and severe forms of the disease can be detrimental to the quality of life of the patients and their surroundings&#46;2 Itching&#44; sleep disturbances&#44; and changes to social interaction behaviors are among the factors that negatively impact these patients&#8217; quality of life&#44; which can lead to a higher risk of psychiatric comorbidity&#44; specifically a higher prevalence of anxiety&#44; depression&#44; and suicidal ideation&#46;<a class="elsevierStyleCrossRefs" href="#bib0110"><span class="elsevierStyleSup">2&#44;3</span></a> Additionally&#44; the economic burden of this disease on the patients and their families is significant&#46;<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">4</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">The management of moderate-to-severe AD is complex and continues to be challenging for clinicians&#46; Due to the emergence of new therapeutic alternatives to treat AD in recent years&#44; including biologic drugs &#40;dupilumab and tralokinumab&#41; and Janus kinase inhibitors &#40;upadacitinib&#44; baricitinib&#44; and abrocitinib&#41;&#44; we decided to study the current survival of cyclosporine &#40;CsA&#41; in the management of this condition&#46; Specifically&#44; we hypothesized that the fact that CsA treatment is a mandatory step for the Spanish National Health System to be authorized to use other systemic treatments for AD <a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">5</span></a> may be associated with a lower survival rate compared to other diseases&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">The objective of this study is to describe the survival of CsA in the management of AD&#44; with the hypothesis that CsA&#8212;prescribed as a necessary step requested by the Spanish National Health System prior to the use of innovative treatments&#8212;may be administered temporarily&#44; resulting in lower survival&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Method</span><p id="par0020" class="elsevierStylePara elsevierViewall">This was a multicenter&#44; observational&#44; and prospective cohort study of the patients enrolled in the Spanish Registry of Atopic Dermatitis &#40;BIOBADATOP&#41; who would have started CsA therapy from March 2020 &#40;the registry starting date&#41; through January 2023&#46;<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">6</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">The aim of the study was to determine the survival time of CsA in moderate-to-severe AD&#46; Survival time was defined as the time between the initiation of the drug and its discontinuation for any reason&#46; Demographic variables&#44; those associated with the disease and the drug&#44; and the reason for its discontinuation were collected&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">As a comparison cohort&#44; data from the Spanish Registry of Systemic Treatments in Psoriasis &#40;BIOBADADERM&#41; were used&#46;<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">7</span></a> The reason for using the BIOBADADERM registry as a comparator was that CsA is also indicated to treat psoriasis&#44; and in this condition&#44; it is not necessary to prescribe it as a step prior to biologic treatments&#44; so its survival should not be impacted by this factor&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">Statistical analysis was performed to obtain the median survival&#44; as well as the 25<span class="elsevierStyleSup">th</span> and 75<span class="elsevierStyleSup">th</span> percentiles of survival&#46; Similarly&#44; Kaplan-Meier survival curves were used to show the survival of both drugs&#46; The log-rank test was used for the comparative analysis of drug survival&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">Statistical analysis was conducted using the Stata 17 statistical software package &#40;StataCorp&#46; 2021&#41;&#46; <span class="elsevierStyleItalic">P</span> values &#60;<span class="elsevierStyleHsp" style=""></span>&#46;05 were statistically significant&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">Both studies were approved by a research ethics committee &#40;BIOBADATOP&#58; CEIC Aragon no&#46; 22&#47;2018&#44; BIOBADADERM&#58; CEIC Hospital Universitario Doce de Octubre no&#46; 216&#47;07&#41;&#44; and all patients gave their prior written informed consent to participate in the study&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Results</span><p id="par0050" class="elsevierStylePara elsevierViewall">A total of 130 patients diagnosed with AD treated with CsA were included &#40;50&#37; men&#59; mean age&#44; 29&#46;3 years&#41;&#46; The baseline EASI &#40;Eczema Area and Severity Index&#41; of those who started CsA treatment was 19&#46;9&#44; and the mean course of the disease when treatment started&#44; 17&#46;9 years&#46; A total of 63&#46;8&#37; of the patients on CsA had previously received treatment with some kind of systemic drug &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46; The CsA median survival in AD was 1 year &#40;95&#37;CI&#44; 0&#46;80-1&#46;28&#41; &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41;&#46; The most frequent reasons for discontinuing CsA were lack of drug efficacy &#40;27&#46;6&#37;&#41;&#44; and the presence of adverse events &#40;27&#46;6&#37;&#41; &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><p id="par0055" class="elsevierStylePara elsevierViewall">In the group of the patients with psoriasis used as a comparator&#44; a total of 150 patients treated with CsA were included &#40;54&#37; men&#59; mean age&#44; 38&#46;3 years&#41;&#46; The baseline PASI &#40;Psoriasis Area and Severity Index&#41; was 12&#46;5&#44; and the mean course of the disease when treatment started&#44; 10&#46;9 years &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46; The median survival of CsA in this group of patients was 0&#46;37 years &#40;4 months&#41; &#40;95&#37;CI&#44; 0&#46;33-0&#46;44&#41; &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41;&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall">In the Kaplan-Meier curve shown in <a class="elsevierStyleCrossRef" href="#fig0005">figure 1</a>&#44; the survival of CsA in AD and psoriasis can be observed&#44; being the survival of CsA significantly higher in the AD than in the psoriasis group &#40;log-rank test&#59; <span class="elsevierStyleItalic">P</span> &#60;<span class="elsevierStyleHsp" style=""></span>&#46;001&#41;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Discussion</span><p id="par0065" class="elsevierStylePara elsevierViewall">AD is one of those diseases that has experienced a significant growth in the development of therapeutic alternatives in recent years&#44; which has led to a therapeutic paradigm shift&#46; Currently&#44; the Spanish National Health System has established criteria for the funding of advanced systemic therapies based on a severity level measured by the EASI score<span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleUnderline">&#62;</span> 21&#44; and previous use of CsA&#44; except for cases contraindicated&#46;<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">5</span></a> These access conditions could be impacting the prescription patterns&#44; potentially resulting in lower CsA survival compared to other diseases&#46; Based on this hypothesis&#44; we studied the survival of CsA in the Spanish registry of systemic treatments of AD from the Spanish Academy of Dermatology and Venereology &#40;AEDV&#41;&#44; and then compared it with that of psoriasis&#46;<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">8</span></a> Contrary to the hypothesis&#44; we saw a higher CsA survival rate in the AD group&#46;</p><p id="par0070" class="elsevierStylePara elsevierViewall">Survival studies show therapeutic management in the real-world routine clinical practice for diseases in which efficacy&#44; safety&#44; and physician preferences are beyond the ideal clinical trial conditions&#46;<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">9</span></a> In recent years&#44; several trials have been published on the survival of classic systemic drugs and biologics to treat AD&#46;<a class="elsevierStyleCrossRefs" href="#bib0105"><span class="elsevierStyleSup">1&#44;10&#8211;17</span></a></p><p id="par0075" class="elsevierStylePara elsevierViewall">The CsA survival data we found after 1 year of treatment are slightly better than those described in the current scientific medical literature available&#46; For example&#44; Van der Schaft et al&#46; reported a 1-year CsA survival rate of 34&#37; &#40;compared to 48&#46;6&#37; from our study&#41;&#44; while Law Ping Man et al&#46; reported a median CsA survival of 8 months &#40;compared to 1 year in our study&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0150"><span class="elsevierStyleSup">10&#44;17</span></a> In a retrospective Italian series of 95 patients with AD on CsA&#44; only 21&#46;02&#37; of the patients were still on this drug on week 72&#46;<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">11</span></a></p><p id="par0080" class="elsevierStylePara elsevierViewall">Recently&#44; the survival of CsA has been compared to dupilumab&#44; with the latter showing higher survival rates&#46;<a class="elsevierStyleCrossRefs" href="#bib0105"><span class="elsevierStyleSup">1&#44;11&#44;13&#44;14&#44;16</span></a> Organ toxicity&#44; drug interactions&#44; the need for monitoring&#44; and the availability of other alternatives with better efficacy and safety profiles are factors that significantly limit the survival of classic immunosuppressors compared to biologic drugs&#46;<a class="elsevierStyleCrossRefs" href="#bib0155"><span class="elsevierStyleSup">11&#44;12&#44;14&#44;16&#44;18</span></a></p><p id="par0085" class="elsevierStylePara elsevierViewall">To interpret drug survival results&#44; it is essential to consider the reasons for their discontinuation&#46; Regarding CsA in the management of AD&#44; the presence of adverse events accounts for 20&#37; to 50&#37; of all discontinuations&#44;<a class="elsevierStyleCrossRefs" href="#bib0165"><span class="elsevierStyleSup">13&#44;15&#8211;17</span></a> which are similar rates to the findings made in our study where we reported a 27&#46;6&#37; discontinuation rate due to adverse events&#46;</p><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Comparison of CsA survival in the management of atopic dermatitis and psoriasis</span><p id="par0090" class="elsevierStylePara elsevierViewall">Regarding the comparison between the two diseases&#44; we should mention that CsA had higher survival in the management of AD compared to psoriasis&#46; We found twice as many patients still on this drug after 1 year of treatment in the AD group &#40;48&#46;6&#37;&#41; vs the psoriasis group &#40;17&#46;2&#37;&#41;&#46; Several factors may contribute to this difference&#44; being the main one the lower number of approved therapeutic alternatives to treat AD&#46; For example&#44; from 2017 through 2021&#44; dupilumab&#44; CsA&#44; and corticosteroids were the only systemic treatments approved by the European Medicines Agency to treat severe AD&#46; Also&#44; we should mention that patients with AD and EASI scores &#60;<span class="elsevierStyleHsp" style=""></span>21 included in the BIOBADATOP registry currently do not have access to funded therapeutic alternatives such as biologic drugs or JAK inhibitors&#44; which irrevocably leads to prolonged CsA courses of treatment&#46;<a class="elsevierStyleCrossRefs" href="#bib0125"><span class="elsevierStyleSup">5&#44;19</span></a> Another factor that may contribute to these findings is the different CsA prescription practices seen in these two conditions&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Limitations and advantages</span><p id="par0095" class="elsevierStylePara elsevierViewall">As limitations of our study&#44; we should acknowledge the small sample size and potential differences in the characteristics of the patients with AD and psoriasis&#46; Other significant and inevitable limitations have to do with the use of drug survival as an indirect measurement of efficacy&#44; safety&#44; or both&#44; which is impacted by multiple external factors such as the availability of other drugs or dosing intervals&#46;<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">20</span></a> However&#44; we should mention the value of this prospective study based on data from numerous centers&#44; since most survival studies published to date are retrospective trials&#46; Also&#44; this study reflects the use of CsA in the management of AD in the real-world routine clinical practice&#44; at a time when the treatment of this condition is at a turning point&#46;</p></span></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Conclusions</span><p id="par0100" class="elsevierStylePara elsevierViewall">In conclusion&#44; we observed a median survival of CsA to treat AD of 1 year&#44; which was higher compared to that of patients with psoriasis&#46; The requirement by the Spanish National Health System for prior CsA use in patients with moderate-to-severe AD to access innovative therapies does not seem to negatively impact survival&#46; Access requirements to advanced systemic therapies could change in the future&#44; likely modifying CsA survival in the management of AD&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Funding</span><p id="par0105" class="elsevierStylePara elsevierViewall">The BIOBADATOP project has been promoted by the Piel Sana Foundation of the Spanish Academy of Dermatology and Venereology &#40;AEDV&#41;&#44; and received financial support from pharmaceutical companies such as Sanofi&#44; Abbvie&#44; Pfizer&#44; and Leo-Pharma&#46; We should mention that the collaborating pharmaceutical companies were not involved in the study design or execution&#59; data curation&#44; management&#44; analysis or interpretation&#59; manuscript preparation&#44; review or approval&#59; or in the decision to submit the manuscript for publication&#46;</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Conflicts of interest</span><p id="par0110" class="elsevierStylePara elsevierViewall">C&#46; Couselo-Rodr&#237;guez has participated as a sub-investigator or speaker in projects sponsored by Abbvie&#44; Sanofi&#44; Leo-Pharma&#44; Lilly&#44; UCB&#44; Novartis&#44; Pierre Fabre&#44; and Janssen&#46; A&#46; Batalla has been involved in training activities and attended courses and conferences sponsored by Abbvie&#44; Celgene&#44; Faes Pharma&#44; Isdin&#44; Janssen&#44; Leo-Pharma&#44; Lethipharma&#44; Lilly&#44; Mylan&#44; Novartis&#44; Pierre Fabre&#44; and Sanofi&#46; Also&#44; she has been a sub-investigator in clinical trials sponsored by Abbvie&#44; Celgene&#44; Leo-Pharma&#44; Lilly&#44; Novartis&#44; Pfizer&#44; and Sanofi&#46; She has also engaged in consulting activities for Abbvie and Sanofi&#46; J&#46;M&#46; Carrascosa has participated as a principal investigator&#47;sub-investigator and&#47;or received honoraria as a speaker and&#47;or member of expert&#44; or steering committees for Abbvie&#44; Novartis&#44; Janssen&#44; Lilly&#44; Sandoz&#44; Amgen&#44; Almirall&#44; BMS&#44; Boehringer Ingelheim&#44; Biogen&#44; and UCB&#46; P&#46; Chicharro has participated in consultations&#44; colloquia&#44; and clinical trials organized by the Janssen Pharmaceuticals&#44; Almirall&#44; Sanofi Genzyme&#44; Lilly&#44; Abbvie&#44; Novartis&#44; Leo-Pharma&#44; and Pfizer-Wyeth&#46; A&#46; Gonz&#225;lez Quesada has participated as a consultant&#44; speaker&#44; and been involved in clinical trials for Abbvie&#44; Pfizer&#44; Novartis&#44; Sanofi&#44; Boehringer&#44; Bristol-Meyer&#44; Leo-Pharma&#44; Janssen&#46; P&#46; de la Cueva has participated as an advisor&#44; and&#47;or investigator&#44; and&#47;or speaker with Abbvie&#44; Almirall&#44; BMS&#44; Boehringer&#44; Celgene&#44; Janssen&#44; Leo-Pharma&#44; Lilly&#44; MSD&#44; Novartis&#44; Novo Nordisk&#44; Pfizer&#44; Roche&#44; Sanofi&#44; and UCB&#46; A&#46;M&#46; Gim&#233;nez-Arnau has served as a medical advisor for Uriach Pharma &#47; Neucor&#44; Genentech&#44; Novartis&#44; FAES&#44; GSK&#44; Sanofi-Regeneron&#44; Amgen&#44; Thermo Fisher Scientific&#44; Almirall&#44; Celldex&#44; and Leo-Pharma&#46; Also&#44; she has participated as a researcher in projects sponsored by Uriach Pharma&#44; Novartis&#44; Instituto Carlos III-FEDER&#44; and been engaged in training activities sponsored by Uriach Pharma&#44; Novartis&#44; Genentech&#44; Menarini&#44; Leopharma&#44; GSK&#44; MSD&#44; Almirall&#44; Sanofi&#44; and Avene&#46; Y&#46; Gilaberte has served as an advisor for Isdin&#44; Roche Posay&#44; and Galderma&#59; given lectures for Almirall&#44; Sanofi&#44; Avene&#44; Rilastil&#44; Lilly&#44; Uriage&#44; Novartis&#44; Cantabria Labs&#59; and participated in research projects for Almirall&#44; Sanofi&#44; Pfizer&#44; Abbvie&#44; and Leo-Pharma&#46; M&#46; Rodr&#237;guez-Serna has participated as a speaker and consultant for Novartis&#44; Sanofi&#44; Abbvie&#44; Pfizer&#44; Lilly&#44; and Leo-Pharma&#59; she has been the principal investigator in clinical trials sponsored by Novartis&#44; Abbvie&#44; and Leo-Pharma&#46; T&#46; Montero-Vilchez has participated as a consultant&#44; in colloquia&#44; and in clinical trials for Abbvie&#44; Almirall&#44; Incyte&#44; Leo-Pharma&#44; Lilly&#44; Novartis&#44; Sanofi&#44; Pfizer-Wyeth&#44; and UCB Pharma and Instituto de Salud Carlos III&#46; M&#46; Elosua-Gonz&#225;lez has been a researcher and&#47;or speaker for Abbvie&#44; Lilly&#44; Galderma&#44; Leo-Pharma&#44; Pfizer&#44; UCB Pharma&#44; and Sanofi Genzyme&#46; J&#46;F&#46; Silvestre-Salvador declared no conflicts of interest regarding this article&#46; M&#46; Munera-Campos has received fees for scientific advisory&#44; presentations&#44; or other related activities from Abbvie&#44; Leo-Pharma&#44; Janssen&#44; Sanofi&#44; and Galderma&#46; She has also served as a principal investigator and sub-investigator in clinical trials sponsored by Lilly&#44; Leo-Pharma&#44; Novartis&#44; Janssen&#44; Sanofi&#44; Pfizer&#44; Abbvie&#44; Almirall&#44; UCB&#44; and Galderma&#46; J&#46; S&#225;nchez-P&#233;rez declared no conflicts of interest regarding this article&#46; G&#46; Carretero declared no conflicts of interest regarding this article either&#46; C&#46; Maule&#243;n-Fern&#225;ndez has participated in clinical trials on atopic dermatitis sponsored by Sanofi and Leo-Pharma&#46; L&#46; Curto-Barredo received speaker fees and advisory fees from Novartis&#44; Sanofi&#44; Abbvie&#44; Lilly&#44; Leo-Pharma&#44; and Menarini&#46; A&#46; Ballano-Ruiz declared no conflicts of interest regarding this article&#46; R&#46; Botella-Estrada participated as a consultant&#44; speaker&#44; or investigator in clinical trials sponsored by Pfizer&#44; Abbvie&#44; Almirall&#44; Novartis&#44; Janssen&#44; Leo-Pharma&#44; Lilly&#44; Celgene&#44; Roche&#44; and SunPharma&#46; S&#46; Arias-Santiago declared no conflicts of interest regarding this article&#46; F&#46;J&#46; Navarro-Trivi&#241;o declared no conflicts of interest regarding this article&#46; G&#46; Roust&#225;n-Gull&#243;n received fees for scientific advisory and courses from Sanofi&#44; Abbvie&#44; Lilly&#44; Pfizer&#44; and Leo-Pharma&#46; I&#46; Betlloch declared no conflicts of interest regarding this article&#46; E&#46; del Alc&#225;zar participated as a speaker and investigator in clinical trials sponsored by Amgen&#44; Almirall&#44; Janssen&#44; Lilly&#44; Leo-Pharma&#44; Novartis&#44; UCB&#44; and Abbvie&#46; M&#46;T&#46; Abalde-Pintos declared no conflicts of interest regarding this article&#46; I&#46; Garc&#237;a-Doval received travel expenses and training at scientific congresses sponsored by Abbvie&#44; MSD&#44; Pfizer&#44; and Sanofi&#46; M&#46;&#193;&#46; Descalzo declared no conflicts of interest regarding this article&#46; &#193;&#46; Fl&#243;rez conducted clinical trials and acted as a speaker and consultant for Abbvie&#44; Almirall&#44; Amgen&#44; Janssen&#44; Leo-Pharma&#44; Lilly&#44; Novartis&#44; Pfizer&#44; Sanofi&#44; and UCB Pharma&#46;</p></span></span>"
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              "titulo" => "Comparison of CsA survival in the management of atopic dermatitis and psoriasis"
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              "titulo" => "Limitations and advantages"
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    "fechaRecibido" => "2023-05-02"
    "fechaAceptado" => "2023-07-03"
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        0 => array:4 [
          "clase" => "keyword"
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            0 => "Atopic dermatitis"
            1 => "Cyclosporine"
            2 => "Survival analysis"
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        0 => array:4 [
          "clase" => "keyword"
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          "palabras" => array:3 [
            0 => "Dermatitis at&#243;pica"
            1 => "Ciclosporina"
            2 => "An&#225;lisis de supervivencia"
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    "resumen" => array:2 [
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        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Background</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">The past 5 years have seen a proliferation of new treatments for atopic dermatitis &#40;AD&#41;&#46; We analyzed recent drug survival data for cyclosporine in this setting&#46; Because the Spanish National Healthcare system requires patients with AD to be treated with cyclosporine before they can be prescribed other systemic treatments&#44; drug survival for cyclosporine may be shorter than in other diseases&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Material and method</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Multicenter&#44; observational&#44; prospective cohort study using data from the Spanish Atopic Dermatitis Registry &#40;BIOBADATOP&#41;&#46; Data from the Spanish Registry of Systemic Treatments in Psoriasis &#40;BIOBADADERM&#41; were used to create a comparison cohort&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">We analyzed data for 130 patients with AD treated with cyclosporine &#40;median drug survival&#44; 1 year&#41;&#46; Median cyclosporine survival in the psoriasis comparison group &#40;150 patients&#41; was 0&#46;37 years&#46; Drug survival was significantly longer in AD than in psoriasis &#40;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>&#46;001&#41;&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusion</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Drug survival of cyclosporine in the BIOBADATOP registry is similar to that described in other series of patients with AD and longer than that observed in the BIOBADADERM psoriasis registry&#46;</p></span>"
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            "titulo" => "Background"
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          1 => array:2 [
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            "titulo" => "Material and method"
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        "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Antecedentes</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Debido a la eclosi&#243;n en el &#250;ltimo quinquenio de nuevas alternativas terap&#233;uticas para la dermatitis at&#243;pica &#40;DA&#41;&#44; nos planteamos estudiar la supervivencia actual de la ciclosporina &#40;CsA&#41; en esta patolog&#237;a&#46; La CsA&#44; como paso necesario solicitado por el Sistema Nacional de Salud de Espa&#241;a para la autorizaci&#243;n de otros tratamientos sist&#233;micos&#44; podr&#237;a presentar una supervivencia menor que en otras enfermedades&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Material y m&#233;todo</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Estudio multic&#233;ntrico&#44; observacional&#44; de cohortes prospectivo para el que se recogieron pacientes incluidos en el Registro Espa&#241;ol de Dermatitis At&#243;pica &#40;BIOBADATOP&#41;&#46; Como cohorte de comparaci&#243;n se emplearon los datos del Registro Espa&#241;ol de tratamientos sist&#233;micos en Psoriasis &#40;BIOBADADERM&#41;&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Se incluyeron 130 pacientes diagnosticados de DA que hab&#237;an recibido CsA &#40;mediana de supervivencia de CsA&#58; 1 a&#241;o&#41;&#46; En el grupo comparador se incluyeron 150 pacientes psori&#225;sicos que hab&#237;an recibido CsA &#40;mediana de supervivencia&#58; 0&#44;37 a&#241;os&#41;&#46; Observamos una mayor supervivencia de la CsA en los pacientes con DA en comparaci&#243;n con los pacientes psori&#225;sicos &#40;p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#41;&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusi&#243;n</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">La supervivencia de la CsA en BIOBADATOP es similar a la descrita en otras series de pacientes con DA&#44; y superior a la observada en los pacientes con psoriasis en el registro BIOBADADERM&#46;</p></span>"
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          "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Kaplan-Meier curve showing the survival of CsA in the management of AD&#44; and psoriasis&#46;</p>"
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          "leyenda" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">AD&#44; atopic dermatitis&#59; CsA&#44; cyclosporine&#59; MTX&#44; methotrexate&#59; NA&#44; not applicable&#59; SD&#44; standard deviation&#46;</p>"
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">AD treated with CsA N &#40;&#37;&#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
                  \t\t\t\t\ttop\n
                  \t\t\t\t">No&#46; of patients&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">130 &#40;100&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">150 &#40;100&#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">Man&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">65 &#40;50&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">81 &#40;54&#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">Previous systemic treatment&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">83 &#40;63&#46;8&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">63 &#40;42&#46;0&#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">Previous treatment with CsA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">31 &#40;23&#46;8&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">16 &#40;10&#46;7&#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">Previous treatment with MTX&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\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 &#40;11&#46;5&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">42 &#40;28&#46;0&#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">Any comorbidity&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">41 &#40;31&#46;5&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">37 &#40;24&#46;7&#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">Age when treatment started &#40;years&#41;&#44; mean &#40;SD&#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">29&#46;3 &#40;13&#46;4&#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">38&#46;3 &#40;14&#46;0&#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">Course of the disease when treatment started &#40;years&#41;&#44; mean &#40;SD&#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">17&#46;9 &#40;11&#46;9&#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">10&#46;9 &#40;10&#46;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">EASI overall score &#40;0-72&#41;&#44; mean &#40;SD&#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">19&#46;9 &#40;11&#46;0&#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">NA&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">PASI overall score &#40;0-72&#41;&#44; mean &#40;SD&#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">NA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\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&#46;5 &#40;7&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
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                0 => "xTab3591266.png"
              ]
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        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Baseline characteristics of patients diagnosed with AD and psoriasis on CsA&#46;</p>"
        ]
      ]
      2 => array:8 [
        "identificador" => "tbl0010"
        "etiqueta" => "Table 2"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
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        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at2"
            "detalle" => "Table "
            "rol" => "short"
          ]
        ]
        "tabla" => array:2 [
          "leyenda" => "<p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">AD&#44; atopic dermatitis&#59; CsA&#44; cyclosporine&#59; NA&#44; data unavailable due to insufficient follow-up&#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">&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  " colspan="2" align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">AD</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " colspan="2" align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Psoriasis</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">No&#46; of patients&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">Value &#40;in years&#41; &#40;95&#37;CI&#41;&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">No&#46; of patients&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">Value &#40;in years&#41; &#40;95&#37;CI&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="5" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Median &#40;p50&#41; drug survival</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>CsA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">130&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\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&#46;00 &#40;0&#46;80-1&#46;28&#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">150&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;37 &#40;0&#46;33-0&#46;44&#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="5" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">25</span><span class="elsevierStyleSup"><span class="elsevierStyleItalic">th</span></span><span class="elsevierStyleItalic">percentile drug survival</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>CsA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">130&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;44 &#40;0&#46;34-0&#46;66&#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">150&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;22 &#40;0&#46;17-1&#46;27&#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="5" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">75</span><span class="elsevierStyleSup"><span class="elsevierStyleItalic">th</span></span><span class="elsevierStyleItalic">percentile drug survival</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>CsA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">130&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\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&#46;56 &#40;1&#46;78-NA&#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">150&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;70 &#40;0&#46;55-0&#46;92&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
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                0 => "xTab3591267.png"
              ]
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        "descripcion" => array:1 [
          "en" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Survival of CsA in AD and psoriasis&#46;</p>"
        ]
      ]
      3 => array:8 [
        "identificador" => "tbl0015"
        "etiqueta" => "Table 3"
        "tipo" => "MULTIMEDIATABLA"
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        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at3"
            "detalle" => "Table "
            "rol" => "short"
          ]
        ]
        "tabla" => array:2 [
          "leyenda" => "<p id="spar0075" class="elsevierStyleSimplePara elsevierViewall">AD&#44; atopic dermatitis&#59; CsA&#44; cyclosporine&#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">CsA&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">No efficacy&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">21 &#40;27&#44;6&#37;&#41;&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">21 &#40;27&#44;6&#37;&#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</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
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Original article
Drug Survival in Cyclosporine Treatment for Moderate to Severe Atopic Dermatitis: Analysis of the Spanish Atopic Dermatitis Registry (BIOBADATOP)
Supervivencia de la ciclosporina en el tratamiento de la dermatitis atópica moderada-grave: Registro Español de Dermatitis Atópica (BIOBADATOP)
C. Couselo-Rodrígueza,b,
Autor para correspondencia
carmen.couselo.rodriguez@sergas.es

Autor para correspondencia.
, A. Batallaa,b, J.M. Carrascosac, P. Chicharrod, A. González-Quesadae, P. de la Cuevaf, A.M. Giménez-Arnaug, Y. Gilaberteh, M. Rodríguez-Sernai, T. Montero-Vilchezj, R. Ruiz-Villaverdek, M. Elosua-Gonzálezl, J.F. Silvestre-Salvadorm, M. Munera-Camposc, J. Sánchez-Pérezd, G. Carreteroe, C. Mauleón-Fernándezf, L. Curto-Barredog, A. Ballano-Ruizh, R. Botella-Estradai..., S. Arias-Santiagoj, F.J. Navarro-Triviñok, G. Roustan-Gullónl, I. Betllochm, E. del Alcázarc, M.T. Abalde-Pintosa,b, J. Suárez-Perezn, I. García-Dovalo,p, M.Á. Descalzoo, Á. Flóreza,bVer más
a Servicio de Dermatología, Complejo Hospitalario Universitario de Pontevedra, Pontevedra, Spain
b Grupo de Investigación DIPO, Instituto de Investigación Sanitaria Galicia Sur (IIS Galicia Sur), SERGAS-UVIGO, Spain
c Servicio de Dermatología, Hospital Universitari Germans Trias i Pujol. Germans Trias I Pujol Research Institute (IGTP), Universitat Autònoma de Barcelona, Badalona, Barcelona, Spain
d Servicio de Dermatología, Hospital Universitario de la Princesa, Madrid, Spain
e Servicio de Dermatología, Hospital Universitario de Gran Canaria Doctor Negrín, Las Palmas de Gran Canaria, Spain
f Servicio de Dermatología, Hospital Universitario Infanta Leonor, Madrid, Spain
g Servicio de Dermatología, Hospital del Mar, IMIM, Universitat Pompeu Fabra, Barcelona, Spain
h Servicio de Dermatología, Hospital Universitario Miguel Servet, Zaragoza, Spain
i Servicio de Dermatología, Hospital Universitario y Politécnico la Fe, Valencia, Spain
j Servicio de Dermatología, Hospital Universitario Virgen de las Nieves, Granada. Instituto de Investigación IBS, Granada, Spain
k Servicio de Dermatología, Hospital Universitario San Cecilio, Granada, Spain
l Servicio de Dermatología, Hospital Universitario Puerta del Hierro, Madrid, Spain
m Servicio de Dermatología, Hospital General Universitario Dr. Balmis, Alicante. ISABIAL, Alicante, Spain
n Servicio de Dermatología, Hospital Clínico de Málaga, Málaga, Spain
o Unidad de Investigación, Fundación Piel Sana AEDV, Spain
p Servicio de Dermatología, Complexo Hospitalario Universitario de Vigo, Vigo, Spain
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        "titulo" => "Supervivencia de la ciclosporina en el tratamiento de la dermatitis at&#243;pica moderada-grave&#58; Registro Espa&#241;ol de Dermatitis At&#243;pica &#40;BIOBADATOP&#41;"
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          "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Kaplan-Meier curve showing the survival of CsA in the management of AD&#44; and psoriasis&#46;</p>"
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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Atopic dermatitis &#40;AD&#41; is a chronic immune-mediated disease believed to affect 20&#37; and 8&#37; of the pediatric and adult populations&#44; respectively&#46;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">1</span></a> Moderate and severe forms of the disease can be detrimental to the quality of life of the patients and their surroundings&#46;2 Itching&#44; sleep disturbances&#44; and changes to social interaction behaviors are among the factors that negatively impact these patients&#8217; quality of life&#44; which can lead to a higher risk of psychiatric comorbidity&#44; specifically a higher prevalence of anxiety&#44; depression&#44; and suicidal ideation&#46;<a class="elsevierStyleCrossRefs" href="#bib0110"><span class="elsevierStyleSup">2&#44;3</span></a> Additionally&#44; the economic burden of this disease on the patients and their families is significant&#46;<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">4</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">The management of moderate-to-severe AD is complex and continues to be challenging for clinicians&#46; Due to the emergence of new therapeutic alternatives to treat AD in recent years&#44; including biologic drugs &#40;dupilumab and tralokinumab&#41; and Janus kinase inhibitors &#40;upadacitinib&#44; baricitinib&#44; and abrocitinib&#41;&#44; we decided to study the current survival of cyclosporine &#40;CsA&#41; in the management of this condition&#46; Specifically&#44; we hypothesized that the fact that CsA treatment is a mandatory step for the Spanish National Health System to be authorized to use other systemic treatments for AD <a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">5</span></a> may be associated with a lower survival rate compared to other diseases&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">The objective of this study is to describe the survival of CsA in the management of AD&#44; with the hypothesis that CsA&#8212;prescribed as a necessary step requested by the Spanish National Health System prior to the use of innovative treatments&#8212;may be administered temporarily&#44; resulting in lower survival&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Method</span><p id="par0020" class="elsevierStylePara elsevierViewall">This was a multicenter&#44; observational&#44; and prospective cohort study of the patients enrolled in the Spanish Registry of Atopic Dermatitis &#40;BIOBADATOP&#41; who would have started CsA therapy from March 2020 &#40;the registry starting date&#41; through January 2023&#46;<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">6</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">The aim of the study was to determine the survival time of CsA in moderate-to-severe AD&#46; Survival time was defined as the time between the initiation of the drug and its discontinuation for any reason&#46; Demographic variables&#44; those associated with the disease and the drug&#44; and the reason for its discontinuation were collected&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">As a comparison cohort&#44; data from the Spanish Registry of Systemic Treatments in Psoriasis &#40;BIOBADADERM&#41; were used&#46;<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">7</span></a> The reason for using the BIOBADADERM registry as a comparator was that CsA is also indicated to treat psoriasis&#44; and in this condition&#44; it is not necessary to prescribe it as a step prior to biologic treatments&#44; so its survival should not be impacted by this factor&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">Statistical analysis was performed to obtain the median survival&#44; as well as the 25<span class="elsevierStyleSup">th</span> and 75<span class="elsevierStyleSup">th</span> percentiles of survival&#46; Similarly&#44; Kaplan-Meier survival curves were used to show the survival of both drugs&#46; The log-rank test was used for the comparative analysis of drug survival&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">Statistical analysis was conducted using the Stata 17 statistical software package &#40;StataCorp&#46; 2021&#41;&#46; <span class="elsevierStyleItalic">P</span> values &#60;<span class="elsevierStyleHsp" style=""></span>&#46;05 were statistically significant&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">Both studies were approved by a research ethics committee &#40;BIOBADATOP&#58; CEIC Aragon no&#46; 22&#47;2018&#44; BIOBADADERM&#58; CEIC Hospital Universitario Doce de Octubre no&#46; 216&#47;07&#41;&#44; and all patients gave their prior written informed consent to participate in the study&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Results</span><p id="par0050" class="elsevierStylePara elsevierViewall">A total of 130 patients diagnosed with AD treated with CsA were included &#40;50&#37; men&#59; mean age&#44; 29&#46;3 years&#41;&#46; The baseline EASI &#40;Eczema Area and Severity Index&#41; of those who started CsA treatment was 19&#46;9&#44; and the mean course of the disease when treatment started&#44; 17&#46;9 years&#46; A total of 63&#46;8&#37; of the patients on CsA had previously received treatment with some kind of systemic drug &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46; The CsA median survival in AD was 1 year &#40;95&#37;CI&#44; 0&#46;80-1&#46;28&#41; &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41;&#46; The most frequent reasons for discontinuing CsA were lack of drug efficacy &#40;27&#46;6&#37;&#41;&#44; and the presence of adverse events &#40;27&#46;6&#37;&#41; &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><p id="par0055" class="elsevierStylePara elsevierViewall">In the group of the patients with psoriasis used as a comparator&#44; a total of 150 patients treated with CsA were included &#40;54&#37; men&#59; mean age&#44; 38&#46;3 years&#41;&#46; The baseline PASI &#40;Psoriasis Area and Severity Index&#41; was 12&#46;5&#44; and the mean course of the disease when treatment started&#44; 10&#46;9 years &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46; The median survival of CsA in this group of patients was 0&#46;37 years &#40;4 months&#41; &#40;95&#37;CI&#44; 0&#46;33-0&#46;44&#41; &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41;&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall">In the Kaplan-Meier curve shown in <a class="elsevierStyleCrossRef" href="#fig0005">figure 1</a>&#44; the survival of CsA in AD and psoriasis can be observed&#44; being the survival of CsA significantly higher in the AD than in the psoriasis group &#40;log-rank test&#59; <span class="elsevierStyleItalic">P</span> &#60;<span class="elsevierStyleHsp" style=""></span>&#46;001&#41;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Discussion</span><p id="par0065" class="elsevierStylePara elsevierViewall">AD is one of those diseases that has experienced a significant growth in the development of therapeutic alternatives in recent years&#44; which has led to a therapeutic paradigm shift&#46; Currently&#44; the Spanish National Health System has established criteria for the funding of advanced systemic therapies based on a severity level measured by the EASI score<span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleUnderline">&#62;</span> 21&#44; and previous use of CsA&#44; except for cases contraindicated&#46;<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">5</span></a> These access conditions could be impacting the prescription patterns&#44; potentially resulting in lower CsA survival compared to other diseases&#46; Based on this hypothesis&#44; we studied the survival of CsA in the Spanish registry of systemic treatments of AD from the Spanish Academy of Dermatology and Venereology &#40;AEDV&#41;&#44; and then compared it with that of psoriasis&#46;<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">8</span></a> Contrary to the hypothesis&#44; we saw a higher CsA survival rate in the AD group&#46;</p><p id="par0070" class="elsevierStylePara elsevierViewall">Survival studies show therapeutic management in the real-world routine clinical practice for diseases in which efficacy&#44; safety&#44; and physician preferences are beyond the ideal clinical trial conditions&#46;<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">9</span></a> In recent years&#44; several trials have been published on the survival of classic systemic drugs and biologics to treat AD&#46;<a class="elsevierStyleCrossRefs" href="#bib0105"><span class="elsevierStyleSup">1&#44;10&#8211;17</span></a></p><p id="par0075" class="elsevierStylePara elsevierViewall">The CsA survival data we found after 1 year of treatment are slightly better than those described in the current scientific medical literature available&#46; For example&#44; Van der Schaft et al&#46; reported a 1-year CsA survival rate of 34&#37; &#40;compared to 48&#46;6&#37; from our study&#41;&#44; while Law Ping Man et al&#46; reported a median CsA survival of 8 months &#40;compared to 1 year in our study&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0150"><span class="elsevierStyleSup">10&#44;17</span></a> In a retrospective Italian series of 95 patients with AD on CsA&#44; only 21&#46;02&#37; of the patients were still on this drug on week 72&#46;<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">11</span></a></p><p id="par0080" class="elsevierStylePara elsevierViewall">Recently&#44; the survival of CsA has been compared to dupilumab&#44; with the latter showing higher survival rates&#46;<a class="elsevierStyleCrossRefs" href="#bib0105"><span class="elsevierStyleSup">1&#44;11&#44;13&#44;14&#44;16</span></a> Organ toxicity&#44; drug interactions&#44; the need for monitoring&#44; and the availability of other alternatives with better efficacy and safety profiles are factors that significantly limit the survival of classic immunosuppressors compared to biologic drugs&#46;<a class="elsevierStyleCrossRefs" href="#bib0155"><span class="elsevierStyleSup">11&#44;12&#44;14&#44;16&#44;18</span></a></p><p id="par0085" class="elsevierStylePara elsevierViewall">To interpret drug survival results&#44; it is essential to consider the reasons for their discontinuation&#46; Regarding CsA in the management of AD&#44; the presence of adverse events accounts for 20&#37; to 50&#37; of all discontinuations&#44;<a class="elsevierStyleCrossRefs" href="#bib0165"><span class="elsevierStyleSup">13&#44;15&#8211;17</span></a> which are similar rates to the findings made in our study where we reported a 27&#46;6&#37; discontinuation rate due to adverse events&#46;</p><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Comparison of CsA survival in the management of atopic dermatitis and psoriasis</span><p id="par0090" class="elsevierStylePara elsevierViewall">Regarding the comparison between the two diseases&#44; we should mention that CsA had higher survival in the management of AD compared to psoriasis&#46; We found twice as many patients still on this drug after 1 year of treatment in the AD group &#40;48&#46;6&#37;&#41; vs the psoriasis group &#40;17&#46;2&#37;&#41;&#46; Several factors may contribute to this difference&#44; being the main one the lower number of approved therapeutic alternatives to treat AD&#46; For example&#44; from 2017 through 2021&#44; dupilumab&#44; CsA&#44; and corticosteroids were the only systemic treatments approved by the European Medicines Agency to treat severe AD&#46; Also&#44; we should mention that patients with AD and EASI scores &#60;<span class="elsevierStyleHsp" style=""></span>21 included in the BIOBADATOP registry currently do not have access to funded therapeutic alternatives such as biologic drugs or JAK inhibitors&#44; which irrevocably leads to prolonged CsA courses of treatment&#46;<a class="elsevierStyleCrossRefs" href="#bib0125"><span class="elsevierStyleSup">5&#44;19</span></a> Another factor that may contribute to these findings is the different CsA prescription practices seen in these two conditions&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Limitations and advantages</span><p id="par0095" class="elsevierStylePara elsevierViewall">As limitations of our study&#44; we should acknowledge the small sample size and potential differences in the characteristics of the patients with AD and psoriasis&#46; Other significant and inevitable limitations have to do with the use of drug survival as an indirect measurement of efficacy&#44; safety&#44; or both&#44; which is impacted by multiple external factors such as the availability of other drugs or dosing intervals&#46;<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">20</span></a> However&#44; we should mention the value of this prospective study based on data from numerous centers&#44; since most survival studies published to date are retrospective trials&#46; Also&#44; this study reflects the use of CsA in the management of AD in the real-world routine clinical practice&#44; at a time when the treatment of this condition is at a turning point&#46;</p></span></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Conclusions</span><p id="par0100" class="elsevierStylePara elsevierViewall">In conclusion&#44; we observed a median survival of CsA to treat AD of 1 year&#44; which was higher compared to that of patients with psoriasis&#46; The requirement by the Spanish National Health System for prior CsA use in patients with moderate-to-severe AD to access innovative therapies does not seem to negatively impact survival&#46; Access requirements to advanced systemic therapies could change in the future&#44; likely modifying CsA survival in the management of AD&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Funding</span><p id="par0105" class="elsevierStylePara elsevierViewall">The BIOBADATOP project has been promoted by the Piel Sana Foundation of the Spanish Academy of Dermatology and Venereology &#40;AEDV&#41;&#44; and received financial support from pharmaceutical companies such as Sanofi&#44; Abbvie&#44; Pfizer&#44; and Leo-Pharma&#46; We should mention that the collaborating pharmaceutical companies were not involved in the study design or execution&#59; data curation&#44; management&#44; analysis or interpretation&#59; manuscript preparation&#44; review or approval&#59; or in the decision to submit the manuscript for publication&#46;</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Conflicts of interest</span><p id="par0110" class="elsevierStylePara elsevierViewall">C&#46; Couselo-Rodr&#237;guez has participated as a sub-investigator or speaker in projects sponsored by Abbvie&#44; Sanofi&#44; Leo-Pharma&#44; Lilly&#44; UCB&#44; Novartis&#44; Pierre Fabre&#44; and Janssen&#46; A&#46; Batalla has been involved in training activities and attended courses and conferences sponsored by Abbvie&#44; Celgene&#44; Faes Pharma&#44; Isdin&#44; Janssen&#44; Leo-Pharma&#44; Lethipharma&#44; Lilly&#44; Mylan&#44; Novartis&#44; Pierre Fabre&#44; and Sanofi&#46; Also&#44; she has been a sub-investigator in clinical trials sponsored by Abbvie&#44; Celgene&#44; Leo-Pharma&#44; Lilly&#44; Novartis&#44; Pfizer&#44; and Sanofi&#46; She has also engaged in consulting activities for Abbvie and Sanofi&#46; J&#46;M&#46; Carrascosa has participated as a principal investigator&#47;sub-investigator and&#47;or received honoraria as a speaker and&#47;or member of expert&#44; or steering committees for Abbvie&#44; Novartis&#44; Janssen&#44; Lilly&#44; Sandoz&#44; Amgen&#44; Almirall&#44; BMS&#44; Boehringer Ingelheim&#44; Biogen&#44; and UCB&#46; P&#46; Chicharro has participated in consultations&#44; colloquia&#44; and clinical trials organized by the Janssen Pharmaceuticals&#44; Almirall&#44; Sanofi Genzyme&#44; Lilly&#44; Abbvie&#44; Novartis&#44; Leo-Pharma&#44; and Pfizer-Wyeth&#46; A&#46; Gonz&#225;lez Quesada has participated as a consultant&#44; speaker&#44; and been involved in clinical trials for Abbvie&#44; Pfizer&#44; Novartis&#44; Sanofi&#44; Boehringer&#44; Bristol-Meyer&#44; Leo-Pharma&#44; Janssen&#46; P&#46; de la Cueva has participated as an advisor&#44; and&#47;or investigator&#44; and&#47;or speaker with Abbvie&#44; Almirall&#44; BMS&#44; Boehringer&#44; Celgene&#44; Janssen&#44; Leo-Pharma&#44; Lilly&#44; MSD&#44; Novartis&#44; Novo Nordisk&#44; Pfizer&#44; Roche&#44; Sanofi&#44; and UCB&#46; A&#46;M&#46; Gim&#233;nez-Arnau has served as a medical advisor for Uriach Pharma &#47; Neucor&#44; Genentech&#44; Novartis&#44; FAES&#44; GSK&#44; Sanofi-Regeneron&#44; Amgen&#44; Thermo Fisher Scientific&#44; Almirall&#44; Celldex&#44; and Leo-Pharma&#46; Also&#44; she has participated as a researcher in projects sponsored by Uriach Pharma&#44; Novartis&#44; Instituto Carlos III-FEDER&#44; and been engaged in training activities sponsored by Uriach Pharma&#44; Novartis&#44; Genentech&#44; Menarini&#44; Leopharma&#44; GSK&#44; MSD&#44; Almirall&#44; Sanofi&#44; and Avene&#46; Y&#46; Gilaberte has served as an advisor for Isdin&#44; Roche Posay&#44; and Galderma&#59; given lectures for Almirall&#44; Sanofi&#44; Avene&#44; Rilastil&#44; Lilly&#44; Uriage&#44; Novartis&#44; Cantabria Labs&#59; and participated in research projects for Almirall&#44; Sanofi&#44; Pfizer&#44; Abbvie&#44; and Leo-Pharma&#46; M&#46; Rodr&#237;guez-Serna has participated as a speaker and consultant for Novartis&#44; Sanofi&#44; Abbvie&#44; Pfizer&#44; Lilly&#44; and Leo-Pharma&#59; she has been the principal investigator in clinical trials sponsored by Novartis&#44; Abbvie&#44; and Leo-Pharma&#46; T&#46; Montero-Vilchez has participated as a consultant&#44; in colloquia&#44; and in clinical trials for Abbvie&#44; Almirall&#44; Incyte&#44; Leo-Pharma&#44; Lilly&#44; Novartis&#44; Sanofi&#44; Pfizer-Wyeth&#44; and UCB Pharma and Instituto de Salud Carlos III&#46; M&#46; Elosua-Gonz&#225;lez has been a researcher and&#47;or speaker for Abbvie&#44; Lilly&#44; Galderma&#44; Leo-Pharma&#44; Pfizer&#44; UCB Pharma&#44; and Sanofi Genzyme&#46; J&#46;F&#46; Silvestre-Salvador declared no conflicts of interest regarding this article&#46; M&#46; Munera-Campos has received fees for scientific advisory&#44; presentations&#44; or other related activities from Abbvie&#44; Leo-Pharma&#44; Janssen&#44; Sanofi&#44; and Galderma&#46; She has also served as a principal investigator and sub-investigator in clinical trials sponsored by Lilly&#44; Leo-Pharma&#44; Novartis&#44; Janssen&#44; Sanofi&#44; Pfizer&#44; Abbvie&#44; Almirall&#44; UCB&#44; and Galderma&#46; J&#46; S&#225;nchez-P&#233;rez declared no conflicts of interest regarding this article&#46; G&#46; Carretero declared no conflicts of interest regarding this article either&#46; C&#46; Maule&#243;n-Fern&#225;ndez has participated in clinical trials on atopic dermatitis sponsored by Sanofi and Leo-Pharma&#46; L&#46; Curto-Barredo received speaker fees and advisory fees from Novartis&#44; Sanofi&#44; Abbvie&#44; Lilly&#44; Leo-Pharma&#44; and Menarini&#46; A&#46; Ballano-Ruiz declared no conflicts of interest regarding this article&#46; R&#46; Botella-Estrada participated as a consultant&#44; speaker&#44; or investigator in clinical trials sponsored by Pfizer&#44; Abbvie&#44; Almirall&#44; Novartis&#44; Janssen&#44; Leo-Pharma&#44; Lilly&#44; Celgene&#44; Roche&#44; and SunPharma&#46; S&#46; Arias-Santiago declared no conflicts of interest regarding this article&#46; F&#46;J&#46; Navarro-Trivi&#241;o declared no conflicts of interest regarding this article&#46; G&#46; Roust&#225;n-Gull&#243;n received fees for scientific advisory and courses from Sanofi&#44; Abbvie&#44; Lilly&#44; Pfizer&#44; and Leo-Pharma&#46; I&#46; Betlloch declared no conflicts of interest regarding this article&#46; E&#46; del Alc&#225;zar participated as a speaker and investigator in clinical trials sponsored by Amgen&#44; Almirall&#44; Janssen&#44; Lilly&#44; Leo-Pharma&#44; Novartis&#44; UCB&#44; and Abbvie&#46; M&#46;T&#46; Abalde-Pintos declared no conflicts of interest regarding this article&#46; I&#46; Garc&#237;a-Doval received travel expenses and training at scientific congresses sponsored by Abbvie&#44; MSD&#44; Pfizer&#44; and Sanofi&#46; M&#46;&#193;&#46; Descalzo declared no conflicts of interest regarding this article&#46; &#193;&#46; Fl&#243;rez conducted clinical trials and acted as a speaker and consultant for Abbvie&#44; Almirall&#44; Amgen&#44; Janssen&#44; Leo-Pharma&#44; Lilly&#44; Novartis&#44; Pfizer&#44; Sanofi&#44; and UCB Pharma&#46;</p></span></span>"
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          "identificador" => "sec0005"
          "titulo" => "Introduction"
        ]
        5 => array:2 [
          "identificador" => "sec0010"
          "titulo" => "Method"
        ]
        6 => array:2 [
          "identificador" => "sec0015"
          "titulo" => "Results"
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        7 => array:3 [
          "identificador" => "sec0020"
          "titulo" => "Discussion"
          "secciones" => array:2 [
            0 => array:2 [
              "identificador" => "sec0025"
              "titulo" => "Comparison of CsA survival in the management of atopic dermatitis and psoriasis"
            ]
            1 => array:2 [
              "identificador" => "sec0030"
              "titulo" => "Limitations and advantages"
            ]
          ]
        ]
        8 => array:2 [
          "identificador" => "sec0035"
          "titulo" => "Conclusions"
        ]
        9 => array:2 [
          "identificador" => "sec0040"
          "titulo" => "Funding"
        ]
        10 => array:2 [
          "identificador" => "sec0045"
          "titulo" => "Conflicts of interest"
        ]
        11 => array:2 [
          "identificador" => "xack758464"
          "titulo" => "Acknowledgments"
        ]
        12 => array:1 [
          "titulo" => "References"
        ]
      ]
    ]
    "pdfFichero" => "main.pdf"
    "tienePdf" => true
    "fechaRecibido" => "2023-05-02"
    "fechaAceptado" => "2023-07-03"
    "PalabrasClave" => array:2 [
      "en" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Keywords"
          "identificador" => "xpalclavsec1846695"
          "palabras" => array:3 [
            0 => "Atopic dermatitis"
            1 => "Cyclosporine"
            2 => "Survival analysis"
          ]
        ]
      ]
      "es" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Palabras clave"
          "identificador" => "xpalclavsec1846694"
          "palabras" => array:3 [
            0 => "Dermatitis at&#243;pica"
            1 => "Ciclosporina"
            2 => "An&#225;lisis de supervivencia"
          ]
        ]
      ]
    ]
    "tieneResumen" => true
    "resumen" => array:2 [
      "en" => array:3 [
        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Background</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">The past 5 years have seen a proliferation of new treatments for atopic dermatitis &#40;AD&#41;&#46; We analyzed recent drug survival data for cyclosporine in this setting&#46; Because the Spanish National Healthcare system requires patients with AD to be treated with cyclosporine before they can be prescribed other systemic treatments&#44; drug survival for cyclosporine may be shorter than in other diseases&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Material and method</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Multicenter&#44; observational&#44; prospective cohort study using data from the Spanish Atopic Dermatitis Registry &#40;BIOBADATOP&#41;&#46; Data from the Spanish Registry of Systemic Treatments in Psoriasis &#40;BIOBADADERM&#41; were used to create a comparison cohort&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">We analyzed data for 130 patients with AD treated with cyclosporine &#40;median drug survival&#44; 1 year&#41;&#46; Median cyclosporine survival in the psoriasis comparison group &#40;150 patients&#41; was 0&#46;37 years&#46; Drug survival was significantly longer in AD than in psoriasis &#40;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>&#46;001&#41;&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusion</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Drug survival of cyclosporine in the BIOBADATOP registry is similar to that described in other series of patients with AD and longer than that observed in the BIOBADADERM psoriasis registry&#46;</p></span>"
        "secciones" => array:4 [
          0 => array:2 [
            "identificador" => "abst0005"
            "titulo" => "Background"
          ]
          1 => array:2 [
            "identificador" => "abst0010"
            "titulo" => "Material and method"
          ]
          2 => array:2 [
            "identificador" => "abst0015"
            "titulo" => "Results"
          ]
          3 => array:2 [
            "identificador" => "abst0020"
            "titulo" => "Conclusion"
          ]
        ]
      ]
      "es" => array:3 [
        "titulo" => "Resumen"
        "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Antecedentes</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Debido a la eclosi&#243;n en el &#250;ltimo quinquenio de nuevas alternativas terap&#233;uticas para la dermatitis at&#243;pica &#40;DA&#41;&#44; nos planteamos estudiar la supervivencia actual de la ciclosporina &#40;CsA&#41; en esta patolog&#237;a&#46; La CsA&#44; como paso necesario solicitado por el Sistema Nacional de Salud de Espa&#241;a para la autorizaci&#243;n de otros tratamientos sist&#233;micos&#44; podr&#237;a presentar una supervivencia menor que en otras enfermedades&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Material y m&#233;todo</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Estudio multic&#233;ntrico&#44; observacional&#44; de cohortes prospectivo para el que se recogieron pacientes incluidos en el Registro Espa&#241;ol de Dermatitis At&#243;pica &#40;BIOBADATOP&#41;&#46; Como cohorte de comparaci&#243;n se emplearon los datos del Registro Espa&#241;ol de tratamientos sist&#233;micos en Psoriasis &#40;BIOBADADERM&#41;&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Se incluyeron 130 pacientes diagnosticados de DA que hab&#237;an recibido CsA &#40;mediana de supervivencia de CsA&#58; 1 a&#241;o&#41;&#46; En el grupo comparador se incluyeron 150 pacientes psori&#225;sicos que hab&#237;an recibido CsA &#40;mediana de supervivencia&#58; 0&#44;37 a&#241;os&#41;&#46; Observamos una mayor supervivencia de la CsA en los pacientes con DA en comparaci&#243;n con los pacientes psori&#225;sicos &#40;p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#41;&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusi&#243;n</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">La supervivencia de la CsA en BIOBADATOP es similar a la descrita en otras series de pacientes con DA&#44; y superior a la observada en los pacientes con psoriasis en el registro BIOBADADERM&#46;</p></span>"
        "secciones" => array:4 [
          0 => array:2 [
            "identificador" => "abst0025"
            "titulo" => "Antecedentes"
          ]
          1 => array:2 [
            "identificador" => "abst0030"
            "titulo" => "Material y m&#233;todo"
          ]
          2 => array:2 [
            "identificador" => "abst0035"
            "titulo" => "Resultados"
          ]
          3 => array:2 [
            "identificador" => "abst0040"
            "titulo" => "Conclusi&#243;n"
          ]
        ]
      ]
    ]
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        "etiqueta" => "Figure 1"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr1.jpeg"
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        "descripcion" => array:1 [
          "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Kaplan-Meier curve showing the survival of CsA in the management of AD&#44; and psoriasis&#46;</p>"
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      ]
      1 => array:8 [
        "identificador" => "tbl0005"
        "etiqueta" => "Table 1"
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          "leyenda" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">AD&#44; atopic dermatitis&#59; CsA&#44; cyclosporine&#59; MTX&#44; methotrexate&#59; NA&#44; not applicable&#59; SD&#44; standard deviation&#46;</p>"
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                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" 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">AD treated with CsA N &#40;&#37;&#41;&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">Psoriasis treated with CsA N &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-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">No&#46; of patients&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">130 &#40;100&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">150 &#40;100&#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">Man&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">65 &#40;50&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">81 &#40;54&#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">Previous systemic treatment&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">83 &#40;63&#46;8&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">63 &#40;42&#46;0&#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">Previous treatment with CsA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">31 &#40;23&#46;8&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">16 &#40;10&#46;7&#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">Previous treatment with MTX&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\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 &#40;11&#46;5&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">42 &#40;28&#46;0&#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">Any comorbidity&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">41 &#40;31&#46;5&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">37 &#40;24&#46;7&#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">Age when treatment started &#40;years&#41;&#44; mean &#40;SD&#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">29&#46;3 &#40;13&#46;4&#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">38&#46;3 &#40;14&#46;0&#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">Course of the disease when treatment started &#40;years&#41;&#44; mean &#40;SD&#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">17&#46;9 &#40;11&#46;9&#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">10&#46;9 &#40;10&#46;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
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                  \t\t\t\t">EASI overall score &#40;0-72&#41;&#44; mean &#40;SD&#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">19&#46;9 &#40;11&#46;0&#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">NA&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">PASI overall score &#40;0-72&#41;&#44; mean &#40;SD&#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">NA&nbsp;\t\t\t\t\t\t\n
                  \t\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">12&#46;5 &#40;7&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
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        "descripcion" => array:1 [
          "en" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Baseline characteristics of patients diagnosed with AD and psoriasis on CsA&#46;</p>"
        ]
      ]
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        "etiqueta" => "Table 2"
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        "tabla" => array:2 [
          "leyenda" => "<p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">AD&#44; atopic dermatitis&#59; CsA&#44; cyclosporine&#59; NA&#44; data unavailable due to insufficient follow-up&#46;</p>"
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                  <table border="0" frame="\n
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                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t" scope="col">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">AD</th><th class="td" title="\n
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                  \t\t\t\t  " colspan="2" align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Psoriasis</th></tr><tr title="table-row"><th class="td" title="\n
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                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&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" scope="col" style="border-bottom: 2px solid black">No&#46; of patients&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">Value &#40;in years&#41; &#40;95&#37;CI&#41;&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">No&#46; of patients&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">Value &#40;in years&#41; &#40;95&#37;CI&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="5" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Median &#40;p50&#41; drug survival</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>CsA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">130&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\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&#46;00 &#40;0&#46;80-1&#46;28&#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">150&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;37 &#40;0&#46;33-0&#46;44&#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="5" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">25</span><span class="elsevierStyleSup"><span class="elsevierStyleItalic">th</span></span><span class="elsevierStyleItalic">percentile drug survival</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>CsA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">130&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;44 &#40;0&#46;34-0&#46;66&#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">150&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;22 &#40;0&#46;17-1&#46;27&#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="5" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">75</span><span class="elsevierStyleSup"><span class="elsevierStyleItalic">th</span></span><span class="elsevierStyleItalic">percentile drug survival</span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>CsA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">130&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\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&#46;56 &#40;1&#46;78-NA&#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">150&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;70 &#40;0&#46;55-0&#46;92&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
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                0 => "xTab3591267.png"
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          "en" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Survival of CsA in AD and psoriasis&#46;</p>"
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          "leyenda" => "<p id="spar0075" class="elsevierStyleSimplePara elsevierViewall">AD&#44; atopic dermatitis&#59; CsA&#44; cyclosporine&#46;</p>"
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            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
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                  \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">CsA&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">No efficacy&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">21 &#40;27&#44;6&#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\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">21 &#40;27&#44;6&#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">Doctor&#39;s orders&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">14 &#40;18&#44;4&#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">Patient&#39;s preference&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\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 &#40;11&#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">Remission of the disease&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6 &#40;7&#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
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Other&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\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 &#40;6&#44;6&#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">Total&nbsp;\t\t\t\t\t\t\n
                  \t\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">76 &#40;100&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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          "en" => "<p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">Reason for suspending CsA in AD&#46;</p>"
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      "titulo" => "References"
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        0 => array:2 [
          "identificador" => "bibs0015"
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            0 => array:3 [
              "identificador" => "bib0105"
              "etiqueta" => "1"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Drug survival of dupilumab compared to cyclosporin in moderate-to-severe atopic dermatitis patients"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "G&#46; Dal Bello"
                            1 => "M&#46; Maurelli"
                            2 => "D&#46; Schena"
                            3 => "G&#46; Girolomoni"
                            4 => "P&#46; Gisondi"
                          ]
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                    0 => array:2 [
                      "doi" => "10.1111/dth.13979"
                      "Revista" => array:5 [
                        "tituloSerie" => "Dermatol Ther"
                        "fecha" => "2020"
                        "volumen" => "33"
                        "paginaInicial" => "e13979"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/32633446"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
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              "identificador" => "bib0110"
              "etiqueta" => "2"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Counting the Burden&#58; Atopic Dermatitis and Health-related Quality of Life"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "F&#46; Ali"
                            1 => "J&#46; Vyas"
                            2 => "A&#46;Y&#46; Finlay"
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                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.2340/00015555-3511"
                      "Revista" => array:6 [
                        "tituloSerie" => "Acta Derm Venereol"
                        "fecha" => "2020"
                        "volumen" => "100"
                        "paginaInicial" => "adv00161"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/32412644"
                            "web" => "Medline"
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                          "pii" => "S0167527314013205"
                          "estado" => "S300"
                          "issn" => "01675273"
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            2 => array:3 [
              "identificador" => "bib0115"
              "etiqueta" => "3"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Atopic dermatitis and psychosocial comorbidities"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "P&#46; Kage"
                            1 => "J&#46;C&#46; Simon"
                            2 => "R&#46; Treudler"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1111/ddg.14029_g"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Dtsch Dermatol Ges"
                        "fecha" => "2020"
                        "volumen" => "18"
                        "paginaInicial" => "93"
                        "paginaFinal" => "102"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/32026651"
                            "web" => "Medline"
                          ]
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            3 => array:3 [
              "identificador" => "bib0120"
              "etiqueta" => "4"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Clinical and Economic Burden of Mild-to-Moderate Atopic Dermatitis in the UK&#58; A Propensity-Score-Matched Case-Control Study"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "F&#46; Toron"
                            1 => "M&#46; Neary"
                            2 => "T&#46;W&#46; Smith"
                            3 => "D&#46; Gruben"
                            4 => "W&#46; Romero"
                            5 => "A&#46; Cha"
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                        ]
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                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1007/s13555-021-00519-7"
                      "Revista" => array:6 [
                        "tituloSerie" => "Dermatol Ther &#40;Heidelb&#41;"
                        "fecha" => "2021"
                        "volumen" => "11"
                        "paginaInicial" => "907"
                        "paginaFinal" => "928"
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                            "web" => "Medline"
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            4 => array:3 [
              "identificador" => "bib0125"
              "etiqueta" => "5"
              "referencia" => array:1 [
                0 => array:1 [
                  "referenciaCompleta" => "BIFIMED&#58; Buscador de la Informaci&#243;n sobre la situaci&#243;n de financiaci&#243;n de los medicamentos&#46; &#91;consulted on April 29&#44; 2023&#93;&#46; Available from <a target="_blank" href="https://www.sanidad.gob.es/gl/profesionales/medicamentos.do">https&#58;&#47;&#47;www&#46;sanidad&#46;gob&#46;es&#47;gl&#47;profesionales&#47;medicamentos&#46;do</a>"
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            ]
            5 => array:3 [
              "identificador" => "bib0130"
              "etiqueta" => "6"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "BIOBADATOP Spanish Atopic Dermatitis Registry&#58; Description and Early Findings"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
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                            1 => "P&#46; Chicharro"
                            2 => "A&#46; Gonz&#225;lez Quesada"
                            3 => "&#193;&#46; Fl&#243;rez Men&#233;ndez"
                            4 => "P&#46; de la Cueva Dovao"
                            5 => "A&#46;M&#46; Gim&#233;nez Arnau"
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                    0 => array:2 [
                      "doi" => "10.1016/j.ad.2023.03.001"
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                        "tituloSerie" => "Actas Dermosifiliogr"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Survival of classic and biological systemic drugs in psoriasis&#58; results of the BIOBADADERM registry and critical analysis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "P&#46; D&#225;vila-Seijo"
                            1 => "E&#46; Daud&#233;n"
                            2 => "G&#46; Carretero"
                            3 => "C&#46; Ferr&#225;ndiz"
                            4 => "F&#46; Vanaclocha"
                            5 => "F&#46;J&#46; G&#243;mez-Garc&#237;a"
                          ]
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                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1111/jdv.13682"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Eur Acad Dermatol Venereol"
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