{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T02:43:00Z","timestamp":1789612980611,"version":"build-2803163510"},"reference-count":41,"publisher":"American Medical Association (AMA)","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Dermatol"],"published-print":{"date-parts":[[2025,1,1]]},"abstract":"<jats:sec id=\"ab-doi240044-4\"><jats:title>Importance<\/jats:title><jats:p>Dupilumab, methotrexate (MTX), and cyclosporine A (CsA) are valuable treatment options for pediatric patients with refractory moderate to severe atopic dermatitis (AD). Yet, comparative data on these treatments in pediatric patients are scarce.<\/jats:p><\/jats:sec><jats:sec id=\"ab-doi240044-5\"><jats:title>Objective<\/jats:title><jats:p>To evaluate drug survival of dupilumab, MTX, and CsA, and identify associated predictors in a multicenter daily practice cohort study of pediatric patients with AD.<\/jats:p><\/jats:sec><jats:sec id=\"ab-doi240044-6\"><jats:title>Design, Setting, and Participants<\/jats:title><jats:p>This multicenter daily practice cohort study included patients with AD aged 2 to 17 years treated with dupilumab, MTX, and\/or CsA in 5 tertiary centers in the Netherlands between 2013 and 2023. Data were extracted from the prospective BioDay and TREAT Netherlands registries and electronic medical records.<\/jats:p><\/jats:sec><jats:sec id=\"ab-doi240044-7\"><jats:title>Exposures<\/jats:title><jats:p>Dupilumab, MTX, CsA.<\/jats:p><\/jats:sec><jats:sec id=\"ab-doi240044-8\"><jats:title>Main Outcomes and Measures<\/jats:title><jats:p>Drug survival was analyzed using Cox proportional hazard regression models. Univariable and multivariable Cox regression analyses were conducted to identify variables associated with drug discontinuation.<\/jats:p><\/jats:sec><jats:sec id=\"ab-doi240044-9\"><jats:title>Results<\/jats:title><jats:p>A total of 502 treatment episodes in 362 unique patients were included, comprising 192 dupilumab episodes, 94 MTX episodes, and 216 CsA episodes. Overall, the mean (SD) age at treatment initiation was 12.9 (3.8) years, and 272 treatment episodes (54.2%) in female patients. The 1-year, 2-year, and 3-year overall drug survival rates, respectively, were 84.1%, 72.3%, and 62.0% for dupilumab; 60.7%, 39.3%, and 25.3% for MTX; and 43.9%, 21.5%, and 10.4% for CsA. Ineffectiveness was the most frequent reason for drug discontinuation, accounting for 178 episodes (35.5%), mostly in patients treated with CsA, followed by adverse effects in 94 patients (18.7%). Treatment with MTX and treatment with CsA were independently associated with a higher risk for drug discontinuation due to ineffectiveness (hazard ratio [HR], 4.45 [95% CI, 2.38-8.34] and HR, 10.88 [95% CI, 6.23-19.02], respectively) and adverse effects (HR, 4.39 [95% CI, 2.05-9.39] and HR, 3.83 [95% CI, 1.85-7.92], respectively) compared to treatment with dupilumab. Patients aged 12 to 17 years starting systemic treatment were independently associated with a higher risk for drug discontinuation due to ineffectiveness (HR, 1.55 [95% CI, 1.10-2.20]) and adverse effects (HR, 2.39 [95% CI, 1.33-4.30]).<\/jats:p><\/jats:sec><jats:sec id=\"ab-doi240044-10\"><jats:title>Conclusions and Relevance<\/jats:title><jats:p>This multicenter daily practice cohort study demonstrated a superior 1-year, 2-year, and 3-year overall drug survival for dupilumab, followed by MTX, with the lowest rates observed for CsA in pediatric patients with AD. This study also identified characteristics associated with discontinuation. These results provide insight into drug survival resulting from the effectiveness, safety, and tolerability of these systemic treatments in pediatric patients with AD and contribute to the optimization of patient outcomes.<\/jats:p><\/jats:sec>","DOI":"10.1001\/jamadermatol.2024.3717","type":"journal-article","created":{"date-parts":[[2024,10,16]],"date-time":"2024-10-16T15:03:43Z","timestamp":1729091023000},"page":"12","source":"Crossref","is-referenced-by-count":10,"title":["Drug Survival of Dupilumab, Methotrexate, and Cyclosporine A in Children With Atopic Dermatitis"],"prefix":"10.1001","volume":"161","author":[{"given":"Lisa P.","family":"van der Rijst","sequence":"first","affiliation":[{"name":"Department of Dermatology and Allergology, National Expertise Center for Atopic Dermatitis, University Medical Center Utrecht, Utrecht, the Netherlands"},{"name":"Department of Dermatology and Allergology, University Medical Center Utrecht, Wilhelmina Children\u2019s Hospital, Utrecht, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esm\u00e9","family":"Kamphuis","sequence":"additional","affiliation":[{"name":"Department of Dermatology, University Medical Center Groningen, Groningen, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie L. A.","family":"Schuttelaar","sequence":"additional","affiliation":[{"name":"Department of Dermatology, University Medical Center Groningen, Groningen, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rimoon","family":"Hurmuz","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Allergology, National Expertise Center for Atopic Dermatitis, University Medical Center Utrecht, Utrecht, the Netherlands"},{"name":"Department of Dermatology and Allergology, University Medical Center Utrecht, Wilhelmina Children\u2019s Hospital, Utrecht, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marieke M. B.","family":"Seyger","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Radboud Medical Center, Nijmegen, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anouk G. M.","family":"Caron","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Amsterdam University Medical Center, Amsterdam, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolaas P. A.","family":"Zuithoff","sequence":"additional","affiliation":[{"name":"Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N. Tan","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Centre of Pediatric Dermatology, Erasmus MC University Medical Centre Rotterdam-Sophia Children\u2019s Hospital, Rotterdam, the Netherlands"},{"name":"Department of Dermatology, Erasmus University Medical Center Rotterdam, Rotterdam, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marijke","family":"Kamsteeg","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Radboud Medical Center, Nijmegen, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marjolein S.","family":"de Bruin-Weller","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Allergology, National Expertise Center for Atopic Dermatitis, University Medical Center Utrecht, Utrecht, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suzanne G. M. 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