{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T16:00:06Z","timestamp":1792425606128,"version":"4.5.0"},"reference-count":26,"publisher":"American Medical Association (AMA)","issue":"8","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Dermatol"],"published-print":{"date-parts":[[2024,8,1]]},"abstract":"Importance<\/jats:title>Moderate to severe atopic dermatitis (AD) is a chronic inflammatory skin disease that often requires continuous long-term systemic management. Long-term safety and efficacy data for treatment options are critically important.<\/jats:p><\/jats:sec>Objective<\/jats:title>To assess the safety and efficacy of dupilumab treatment for up to 5 years in adults with moderate to severe AD.<\/jats:p><\/jats:sec>Design, Setting, and Participants<\/jats:title>The 5-year LIBERTY AD open-label extension study was conducted from September 2013 to June 2022 at 550 sites in 28 countries. The study enrolled adult patients with moderate to severe AD who had participated in previous dupilumab clinical trials. Data were analyzed from August 2022 to February 2023.<\/jats:p><\/jats:sec>Exposures<\/jats:title>At enrollment, patients initiated a regimen of subcutaneous dupilumab, 200 mg, weekly (400-mg loading dose). The regimen was amended in June 2014 to dupilumab, 300 mg, weekly (600-mg loading dose) based on a dose-ranging study and again in November 2019 to dupilumab, 300 mg, every 2 weeks to align with the regulatory regimen approvals.<\/jats:p><\/jats:sec>Main Outcomes and Measures<\/jats:title>The primary end points were the incidence and rate of treatment-emergent adverse events (TEAEs). Key secondary end points included incidence and rate of serious TEAEs and adverse events of special interest, proportion of patients achieving an Investigator\u2019s Global Assessment (IGA) score of 0 or 1 (clear or almost clear), and proportion of patients with 75% or more improvement in the Eczema Area and Severity Index (EASI) from the parent study baseline.<\/jats:p><\/jats:sec>Results<\/jats:title>A total of 2677 patients were enrolled and treated in the open-label extension study; 1611 (60.2%) were male, and the mean (SD) age was 39.2 (13.4) years. A total of 334 patients (12.5%) completed treatment up to week 260. The most common reasons for withdrawal were due to regulatory approval of dupilumab in compliance with the study protocol (810 of 1380 [58.7%]), patient withdrawal (248 of 1380 [18.0%]), and adverse events (116 of 1380 [8.4%]). Exposure-adjusted rates of TEAEs were generally stable or declined throughout the study. Common TEAEs (incidence of 5% or greater) included nasopharyngitis, worsening AD, upper respiratory tract infection, conjunctivitis, conjunctivitis allergic, headache, oral herpes, and injection-site reaction. At week 260, 220 of 326 patients (67.5%) achieved an IGA score of 0 or 1 and 288 of 324 (88.9%) achieved 75% or greater improvement in the EASI. The mean (SD) EASI score was 16.39 (14.60) at baseline and 2.75 (5.62) at end of study.<\/jats:p><\/jats:sec>Conclusions and Relevance<\/jats:title>In this study, there was sustained safety and efficacy of continuous long-term dupilumab treatment for adults with moderate to severe AD.<\/jats:p><\/jats:sec>","DOI":"10.1001\/jamadermatol.2024.1536","type":"journal-article","created":{"date-parts":[[2024,7,10]],"date-time":"2024-07-10T15:05:01Z","timestamp":1720623901000},"page":"805","source":"Crossref","is-referenced-by-count":75,"title":["Dupilumab in Adults With Moderate to Severe Atopic Dermatitis"],"prefix":"10.1001","volume":"160","author":[{"given":"Lisa A.","family":"Beck","sequence":"first","affiliation":[{"name":"Department of Dermatology, University of Rochester Medical Center, Rochester, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Bissonnette","sequence":"additional","affiliation":[{"name":"Innovaderm Research, Montreal, Quebec, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mette","family":"Deleuran","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Aarhus University Hospital, Aarhus, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takeshi","family":"Nakahara","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine, Kyushu University, Fukuoka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryszard","family":"Galus","sequence":"additional","affiliation":[{"name":"Department of Histology and Embryology, Medical University of Warsaw, Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Coleman","sequence":"additional","affiliation":[{"name":"Regeneron Pharmaceuticals Inc, Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guy","family":"Gherardi","sequence":"additional","affiliation":[{"name":"Sanofi, Reading, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Xiao","sequence":"additional","affiliation":[{"name":"Regeneron Pharmaceuticals Inc, Tarrytown, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Dingman","sequence":"additional","affiliation":[{"name":"Regeneron Pharmaceuticals Inc, Tarrytown, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Xu","sequence":"additional","affiliation":[{"name":"Sanofi, Bridgewater, New Jersey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Avetisova","sequence":"additional","affiliation":[{"name":"Regeneron Pharmaceuticals Inc, Tarrytown, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ariane","family":"Dubost-Brama","sequence":"additional","affiliation":[{"name":"Sanofi, Chilly-Mazarin, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arsalan","family":"Shabbir","sequence":"additional","affiliation":[{"name":"Regeneron Pharmaceuticals Inc, Tarrytown, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"10","reference":[{"issue":"1","key":"doi240015r1","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41572-018-0001-z","article-title":"Atopic dermatitis.","volume":"4","author":"Weidinger","year":"2018","journal-title":"Nat Rev Dis Primers"},{"issue":"6","key":"doi240015r2","doi-asserted-by":"publisher","first-page":"1519","DOI":"10.1016\/j.jaip.2017.08.005","article-title":"Expert perspectives on management of moderate-to-severe atopic dermatitis: a multidisciplinary consensus addressing current and emerging therapies.","volume":"5","author":"Boguniewicz","year":"2017","journal-title":"J Allergy Clin Immunol Pract"},{"issue":"4","key":"doi240015r3","doi-asserted-by":"publisher","first-page":"427","DOI":"10.1007\/s40257-022-00701-3","article-title":"JAK in the [black] box: a dermatology perspective on systemic JAK inhibitor safety.","volume":"23","author":"Elmariah","year":"2022","journal-title":"Am J Clin Dermatol"},{"issue":"14","key":"doi240015r4","doi-asserted-by":"publisher","first-page":"5147","DOI":"10.1073\/pnas.1323896111","article-title":"Precise and in situ genetic humanization of 6 Mb of mouse immunoglobulin genes.","volume":"111","author":"Macdonald","year":"2014","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"14","key":"doi240015r5","doi-asserted-by":"publisher","first-page":"5153","DOI":"10.1073\/pnas.1324022111","article-title":"Mice with megabase humanization of their immunoglobulin genes generate antibodies as efficiently as normal mice.","volume":"111","author":"Murphy","year":"2014","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"10086","key":"doi240015r7","doi-asserted-by":"publisher","first-page":"2287","DOI":"10.1016\/S0140-6736(17)31191-1","article-title":"Long-term management of moderate-to-severe atopic dermatitis with dupilumab and concomitant topical corticosteroids (LIBERTY AD CHRONOS): a 1-year, randomised, double-blinded, placebo-controlled, phase 3 trial.","volume":"389","author":"Blauvelt","year":"2017","journal-title":"Lancet"},{"issue":"3","key":"doi240015r8","doi-asserted-by":"publisher","first-page":"393","DOI":"10.1007\/s40257-022-00685-0","article-title":"Dupilumab provides acceptable safety and sustained efficacy for up to 4 years in an open-label study of adults with moderate-to-severe atopic dermatitis.","volume":"23","author":"Beck","year":"2022","journal-title":"Am J Clin Dermatol"},{"issue":"2","key":"doi240015r10","doi-asserted-by":"publisher","first-page":"377","DOI":"10.1016\/j.jaad.2019.07.074","article-title":"Dupilumab shows long-term safety and efficacy in patients with moderate to severe atopic dermatitis enrolled in a phase 3 open-label extension study.","volume":"82","author":"Deleuran","year":"2020","journal-title":"J Am Acad Dermatol"},{"issue":"4","key":"doi240015r11","doi-asserted-by":"publisher","first-page":"567","DOI":"10.1007\/s40257-020-00527-x","article-title":"Dupilumab provides favorable safety and sustained efficacy for up to 3 years in an open-label study of adults with moderate-to-severe atopic dermatitis.","volume":"21","author":"Beck","year":"2020","journal-title":"Am J Clin Dermatol"},{"issue":"24","key":"doi240015r12","doi-asserted-by":"publisher","first-page":"2335","DOI":"10.1056\/NEJMoa1610020","article-title":"Two phase 3 trials of dupilumab versus placebo in atopic dermatitis.","volume":"375","author":"Simpson","year":"2016","journal-title":"N Engl J Med"},{"issue":"10013","key":"doi240015r13","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1016\/S0140-6736(15)00388-8","article-title":"Efficacy and safety of dupilumab in adults with moderate-to-severe atopic dermatitis inadequately controlled by topical treatments: a randomised, placebo-controlled, dose-ranging phase 2b trial.","volume":"387","author":"Tha\u00e7i","year":"2016","journal-title":"Lancet"},{"issue":"5","key":"doi240015r14","doi-asserted-by":"publisher","first-page":"1083","DOI":"10.1111\/bjd.2018.178.issue-5","article-title":"Dupilumab with concomitant topical corticosteroid treatment in adults with atopic dermatitis with an inadequate response or intolerance to ciclosporin A or when this treatment is medically inadvisable: a placebo-controlled, randomized phase III clinical trial (LIBERTY AD CAF\u00c9).","volume":"178","author":"de Bruin-Weller","year":"2018","journal-title":"Br J Dermatol"},{"issue":"2","key":"doi240015r15","doi-asserted-by":"publisher","first-page":"130","DOI":"10.1056\/NEJMoa1314768","article-title":"Dupilumab treatment in adults with moderate-to-severe atopic dermatitis.","volume":"371","author":"Beck","year":"2014","journal-title":"N Engl J Med"},{"issue":"1","key":"doi240015r16","doi-asserted-by":"publisher","first-page":"158","DOI":"10.1016\/j.jaad.2018.07.048","article-title":"Dupilumab does not affect correlates of vaccine-induced immunity: a randomized, placebo-controlled trial in adults with moderate-to-severe atopic dermatitis.","volume":"80","author":"Blauvelt","year":"2019","journal-title":"J Am Acad Dermatol"},{"issue":"1","key":"doi240015r17","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1111\/bjd.v182.1","article-title":"Dupilumab in adolescents with uncontrolled moderate-to-severe atopic dermatitis: results from a phase IIa open-label trial and subsequent phase III open-label extension.","volume":"182","author":"Cork","year":"2020","journal-title":"Br J Dermatol"},{"issue":"6","key":"doi240015r18","doi-asserted-by":"publisher","first-page":"1146","DOI":"10.1002\/cpt.2018.104.issue-6","article-title":"Evaluation of potential disease-mediated drug\u2013drug interaction in patients with moderate-to-severe atopic dermatitis receiving dupilumab.","volume":"104","author":"Davis","year":"2018","journal-title":"Clin Pharmacol Ther"},{"issue":"1","key":"doi240015r19","doi-asserted-by":"publisher","first-page":"155","DOI":"10.1016\/j.jaci.2018.08.022","article-title":"Dupilumab progressively improves systemic and cutaneous abnormalities in patients with atopic dermatitis.","volume":"143","author":"Guttman-Yassky","year":"2019","journal-title":"J Allergy Clin Immunol"},{"issue":"6","key":"doi240015r20","doi-asserted-by":"publisher","first-page":"1293","DOI":"10.1016\/j.jaci.2014.10.013","article-title":"Dupilumab improves the molecular signature in skin of patients with moderate-to-severe atopic dermatitis.","volume":"134","author":"Hamilton","year":"2014","journal-title":"J Allergy Clin Immunol"},{"issue":"2","key":"doi240015r21","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1001\/jamadermatol.2019.3617","article-title":"Efficacy and safety of multiple dupilumab dose regimens after initial successful treatment in patients with atopic dermatitis: a randomized clinical trial.","volume":"156","author":"Worm","year":"2020","journal-title":"JAMA Dermatol"},{"issue":"2","key":"doi240015r23","doi-asserted-by":"publisher","first-page":"130","DOI":"10.1056\/NEJMoa1314768","article-title":"Dupilumab treatment in adults with moderate-to-severe atopic dermatitis.","volume":"371","author":"Beck","year":"2014","journal-title":"N Engl J Med"},{"issue":"1","key":"doi240015r24","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1016\/j.jaad.2020.08.051","article-title":"Real-world evidence of dupilumab efficacy and risk of adverse events: a systematic review and meta-analysis.","volume":"84","author":"Halling","year":"2021","journal-title":"J Am Acad Dermatol"},{"issue":"2","key":"doi240015r25","doi-asserted-by":"publisher","first-page":"486","DOI":"10.1016\/j.jaad.2021.09.029","article-title":"Dupilumab-induced ocular surface disease: a systematic review.","volume":"86","author":"Fachler","year":"2022","journal-title":"J Am Acad Dermatol"},{"issue":"3","key":"doi240015r26","doi-asserted-by":"publisher","first-page":"459","DOI":"10.1111\/bjd.v181.3","article-title":"Conjunctivitis in dupilumab clinical trials.","volume":"181","author":"Akinlade","year":"2019","journal-title":"Br J Dermatol"},{"key":"doi240015r6","unstructured":"Regeneron Pharmaceuticals Inc. Dupixent (dupilumab) highlights of prescribing information. Accessed August 3, 2023. https:\/\/www.regeneron.com\/downloads\/dupixent_fpi.pdf"},{"key":"doi240015r9","unstructured":"Open-label study of dupilumab in patients with atopic dermatitis. ClinicalTrials.gov identifier: NCT01949311. Updated October 17, 2023. Accessed May 30, 2024. https:\/\/clinicaltrials.gov\/study\/NCT01949311"},{"key":"doi240015r22","unstructured":"European Medicines Agency. Dupixent (dupilumab) summary of product characteristics. Accessed August 3, 2023. https:\/\/www.ema.europa.eu\/en\/documents\/product-information\/dupixent-epar-product-information_en.pdf"}],"container-title":["JAMA Dermatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/jamanetwork.com\/journals\/jamadermatology\/articlepdf\/2820911\/jamadermatology_beck_2024_oi_240015_1723648291.50768.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,8,21]],"date-time":"2024-08-21T22:44:25Z","timestamp":1724280265000},"score":1,"resource":{"primary":{"URL":"https:\/\/jamanetwork.com\/journals\/jamadermatology\/fullarticle\/2820911"}},"subtitle":["A 5-Year Open-Label Extension Study"],"short-title":[],"issued":{"date-parts":[[2024,8,1]]},"references-count":26,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2024,8,1]]}},"URL":"https:\/\/doi.org\/10.1001\/jamadermatol.2024.1536","relation":{},"ISSN":["2168-6068"],"issn-type":[{"value":"2168-6068","type":"print"}],"subject":[],"published":{"date-parts":[[2024,8,1]]}}}