{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T15:48:12Z","timestamp":1792597692179,"version":"4.5.0"},"reference-count":34,"publisher":"American Medical Association (AMA)","issue":"10","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Dermatol"],"published-print":{"date-parts":[[2026,10,1]]},"abstract":"\n Importance<\/jats:title>\n Alopecia areata (AA) is a chronic, systemic immune-mediated disease characterized by nonscarring hair loss. Many patients do not experience improvements with available treatment options and only ritlecitinib is approved for adolescent patients; therefore, there remains a clear unmet need for additional and improved systemic therapies.<\/jats:p>\n <\/jats:sec>\n \n Objective<\/jats:title>\n To evaluate the efficacy and safety of upadacitinib\u2014an oral selective Janus kinase inhibitor\u2014in adult and adolescent patients with severe AA.<\/jats:p>\n <\/jats:sec>\n \n Design, Setting, and Participants<\/jats:title>\n This global clinical program included 2 parallel phase 3 replicate randomized clinical trials (UP-AA1 and UP-AA2) conducted from October 2023 to July 2025, to evaluate upadacitinib in adolescent and adult patients (age 12 to &amp;lt;64 years old) with severe AA, defined as a Severity of Alopecia Tool (SALT) score of 50 or greater. Both trials included a 24-week placebo-controlled, double-blinded treatment period (period A) and a 28-week blinded extension treatment period (period B). Data were analyzed from July 2025 to October 2025.<\/jats:p>\n <\/jats:sec>\n \n Interventions<\/jats:title>\n Eligible patients were randomized 2:2:1 to once daily 15- or 30-mg upadacitinib or matching placebo.<\/jats:p>\n <\/jats:sec>\n \n Main Outcomes and Measures<\/jats:title>\n Achievement of (multiplicity controlled) SALT score of 20 or less at week 24. Multiplicity-controlled secondary efficacy end points included achievement of improvements in clinician-reported outcomes for eyebrows and eyelashes; achievement of SALT scores of 20 or less at weeks 4, 8, and 12; achievement of SALT score of 10 or less; SALT score 0 at week 24; patients\u2019 global impression of change of AA score of much better or moderately better at weeks 4 and 24; and other AA-specific health-related quality of life measures at week 24.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n A total of 1399 patients were randomized (mean [range] age, 36 [12-64] years; 826 female [59.0%]), 676 patients from the UP-AA1 and 723 patients from the UP-AA2, to either 15-mg upadacitinib (270 and 289 patients, respectively), 30-mg upadacitinib (271 and 289), or placebo (135 and 145). Their mean (SD) SALT score was 83.9 (18.9) at baseline. The proportion of patients who achieved SALT score of 20 or less at week 24 was significantly higher for the 15-mg upadacitinib (122 [45.2%] and 129 [44.6%]) and the 30-mg upadacitinib (149 [55.0%] and 157 [54.3%]) groups, respectively, than for the placebo (2 [1.5%] and 5 [3.4%]) group. The safety profile of both doses was similar in adults and adolescents and consistent with approved indications; no new safety findings were identified. Treatment-emergent adverse events reported by more than 5% of patients in any treatment group were upper respiratory tract infection, acne, elevated blood creatine phosphokinase, and nasopharyngitis. Across both studies, treatment-emergent serious adverse events occurred in 9 (1.6%), 13 (2.3%), and 1 (0.4%) of patients receiving 15-mg upadacitinib , 30-mg upadacitinib, or placebo, respectively.<\/jats:p>\n <\/jats:sec>\n \n Conclusions and Relevance<\/jats:title>\n In these 2 parallel phase 3 replicate randomized clinical trials, upadacitinib demonstrated a positive benefit-risk profile in adults and adolescents with severe AA. Upadacitinib may be a potentially effective treatment option for this patient population.<\/jats:p>\n <\/jats:sec>\n \n Trial Registration<\/jats:title>\n \n ClinicalTrials.gov Identifier:\n NCT06012240<\/jats:ext-link>\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1001\/jamadermatol.2026.2853","type":"journal-article","created":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T15:00:23Z","timestamp":1786546823000},"page":"1006","source":"Crossref","is-referenced-by-count":1,"title":["Upadacitinib for Severe Alopecia Areata in Adults and Adolescents"],"prefix":"10.1001","volume":"162","author":[{"given":"Arash","family":"Mostaghimi","sequence":"first","affiliation":[{"name":"Department of Dermatology, Brigham and Women\u2019s Hospital, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melinda J.","family":"Gooderham","sequence":"additional","affiliation":[{"name":"SKiN Centre for Dermatology, Peterborough, Ontario, Canada"},{"name":"Probity Medical Research, Peterborough, Ontario, Canada"},{"name":"Department of Medicine, Queen\u2019s University, Kingston, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles","family":"Lynde","sequence":"additional","affiliation":[{"name":"Lynde Institute for Dermatology & Lynderm Research, Markham, Ontario, Canada"},{"name":"Division of Dermatology, Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada"},{"name":"Probity Medical Research, Markham, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rodney","family":"Sinclair","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Melbourne, Melbourne, Victoria, Australia"},{"name":"Sinclair Dermatology, Melbourne, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brett","family":"King","sequence":"additional","affiliation":[{"name":"Dermatology Physicians of Connecticut, Fairfield"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Hordinsky","sequence":"additional","affiliation":[{"name":"Department of Dermatology, University of Minnesota Medical School, Minneapolis"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lidia","family":"Rudnicka","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Medical University of Warsaw, Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emma","family":"Guttman-Yassky","sequence":"additional","affiliation":[{"name":"Department of Dermatology and the Laboratory for Inflammatory Skin Diseases, Icahn School of Medicine at Mount Sinai, New York, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rocco","family":"Serrao","sequence":"additional","affiliation":[{"name":"Dermatologists of Southwest Ohio, Mason"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manabu","family":"Ohyama","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Kyorin University School of Medicine, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingqi","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Dermatology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nina","family":"Magnolo","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Venereology, University Hospital M\u00fcnster, M\u00fcnster, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ohsang","family":"Kwon","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Seoul National University College of Medicine, Seoul, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Oddi","sequence":"additional","affiliation":[{"name":"AbbVie Italy, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebastian","family":"Meerwein","sequence":"additional","affiliation":[{"name":"AbbVie Deutschland GmbH & Co. KG, Ludwigshafen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed M.","family":"Soliman","sequence":"additional","affiliation":[{"name":"AbbVie Inc, North Chicago, Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xianwei","family":"Bu","sequence":"additional","affiliation":[{"name":"AbbVie Inc, North Chicago, Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenyang","family":"Duan","sequence":"additional","affiliation":[{"name":"AbbVie Inc, North Chicago, Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianshuang","family":"Wu","sequence":"additional","affiliation":[{"name":"AbbVie Inc, North Chicago, Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henrique D.","family":"Teixeira","sequence":"additional","affiliation":[{"name":"AbbVie Inc, North Chicago, Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Lazar","sequence":"additional","affiliation":[{"name":"AbbVie Deutschland GmbH & Co. KG, Ludwigshafen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thierry","family":"Passeron","sequence":"additional","affiliation":[{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale\u2212U 2065, Centre M\u00e9diterran\u00e9en de M\u00e9decine Mol\u00e9culaire, C\u00f4te d\u2019Azur University, Nice, France"},{"name":"Department of Dermatology, Centre Hospitalier Universitaire de Nice, C\u00f4te d\u2019Azur University, Nice, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"10","reference":[{"key":"doi260034r1","first-page":"397","article-title":"Epidemiology and burden of alopecia areata: a systematic review.","volume":"8","author":"Villasante Fricke","year":"2015","journal-title":"Clin Cosmet Investig Dermatol"},{"issue":"1","key":"doi260034r2","doi-asserted-by":"publisher","first-page":"17011","DOI":"10.1038\/nrdp.2017.11","article-title":"Alopecia areata.","volume":"3","author":"Pratt","year":"2017","journal-title":"Nat Rev Dis Primers"},{"issue":"4","key":"doi260034r3","doi-asserted-by":"publisher","first-page":"411","DOI":"10.1001\/jamadermatol.2023.0002","article-title":"Trends in prevalence and incidence of alopecia areata, alopecia totalis, and alopecia universalis among adults and children in a US employer-sponsored insured population.","volume":"159","author":"Mostaghimi","year":"2023","journal-title":"JAMA Dermatol"},{"issue":"1","key":"doi260034r4","doi-asserted-by":"publisher","first-page":"162","DOI":"10.1016\/j.jaad.2020.06.047","article-title":"Psychosocial and psychiatric comorbidities and health-related quality of life in alopecia areata: a systematic review.","volume":"85","author":"Toussi","year":"2021","journal-title":"J Am Acad Dermatol"},{"issue":"1","key":"doi260034r5","doi-asserted-by":"publisher","first-page":"285","DOI":"10.1007\/s13555-022-00864-1","article-title":"The association of alopecia areata-related emotional symptoms with work productivity and daily activity among patients with alopecia areata.","volume":"13","author":"Gandhi","year":"2023","journal-title":"Dermatol Ther (Heidelb)"},{"issue":"3","key":"doi260034r6","doi-asserted-by":"publisher","first-page":"867","DOI":"10.1007\/s13555-021-00512-0","article-title":"Patient perspectives of the social, emotional and functional impact of alopecia areata: a systematic literature review.","volume":"11","author":"Mostaghimi","year":"2021","journal-title":"Dermatol Ther (Heidelb)"},{"issue":"5","key":"doi260034r7","doi-asserted-by":"publisher","first-page":"1040","DOI":"10.1016\/j.jaad.2019.05.086","article-title":"Association between alopecia areata, anxiety, and depression: a systematic review and meta-analysis.","volume":"88","author":"Okhovat","year":"2023","journal-title":"J Am Acad Dermatol"},{"issue":"11","key":"doi260034r8","doi-asserted-by":"publisher","first-page":"1488","DOI":"10.1001\/archderm.1987.01660350088019","article-title":"Evaluation of oral minoxidil in the treatment of alopecia areata.","volume":"123","author":"Fiedler-Weiss","year":"1987","journal-title":"Arch Dermatol"},{"issue":"4","key":"doi260034r9","doi-asserted-by":"publisher","first-page":"403","DOI":"10.1001\/jamadermatol.2022.6687","article-title":"Efficacy of methotrexate alone vs methotrexate plus low-dose prednisone in patients with alopecia areata totalis or universalis: a 2-step double-blind randomized clinical trial.","volume":"159","author":"Joly","year":"2023","journal-title":"JAMA Dermatol"},{"issue":"11","key":"doi260034r10","doi-asserted-by":"publisher","first-page":"2606","DOI":"10.1111\/jdv.16858","article-title":"Utility of azathioprine, methotrexate and cyclosporine as steroid-sparing agents in chronic alopecia areata: a retrospective study of continuation rates in 138 patients.","volume":"34","author":"Lai","year":"2020","journal-title":"J Eur Acad Dermatol Venereol"},{"issue":"5","key":"doi260034r11","doi-asserted-by":"publisher","first-page":"2623","DOI":"10.4049\/jimmunol.178.5.2623","article-title":"The JAK-STAT signaling pathway: input and output integration.","volume":"178","author":"Murray","year":"2007","journal-title":"J Immunol"},{"issue":"7","key":"doi260034r12","doi-asserted-by":"publisher","first-page":"961","DOI":"10.1517\/13543784.2012.690029","article-title":"JAK inhibition for the treatment of rheumatoid arthritis: a new era in oral DMARD therapy.","volume":"21","author":"Vaddi","year":"2012","journal-title":"Expert Opin Investig Drugs"},{"issue":"4","key":"doi260034r13","doi-asserted-by":"publisher","first-page":"487","DOI":"10.1007\/s00281-017-0623-3","article-title":"Future therapeutic targets in rheumatoid arthritis?","volume":"39","author":"Cheung","year":"2017","journal-title":"Semin Immunopathol"},{"issue":"10","key":"doi260034r14","doi-asserted-by":"publisher","first-page":"1047","DOI":"10.1080\/1744666X.2016.1189826","article-title":"Progress in understanding the safety and efficacy of Janus kinase inhibitors for treatment of rheumatoid arthritis.","volume":"12","author":"Iwata","year":"2016","journal-title":"Expert Rev Clin Immunol"},{"issue":"5","key":"doi260034r15","doi-asserted-by":"publisher","first-page":"521","DOI":"10.1007\/s40265-017-0701-9","article-title":"JAK-STAT signaling as a target for inflammatory and autoimmune diseases: current and future prospects.","volume":"77","author":"Banerjee","year":"2017","journal-title":"Drugs"},{"issue":"5","key":"doi260034r16","doi-asserted-by":"publisher","first-page":"1783","DOI":"10.1093\/rheumatology\/keab740","article-title":"A review of JAK-STAT signalling in the pathogenesis of spondyloarthritis and the role of JAK inhibition.","volume":"61","author":"McInnes","year":"2022","journal-title":"Rheumatology (Oxford)"},{"issue":"2","key":"doi260034r17","doi-asserted-by":"publisher","first-page":"e61","DOI":"10.1111\/ijd.16342","article-title":"Assessment of alopecia areata universalis successfully treated with upadacitinib.","volume":"62","author":"Gori","year":"2023","journal-title":"Int J Dermatol"},{"issue":"11","key":"doi260034r18","doi-asserted-by":"publisher","first-page":"e416","DOI":"10.1111\/ijd.16316","article-title":"Concurrent chronic alopecia areata and severe atopic dermatitis successfully treated with upadacitinib.","volume":"61","author":"Asfour","year":"2022","journal-title":"Int J Dermatol"},{"key":"doi260034r19","doi-asserted-by":"publisher","DOI":"10.1177\/2050313X221138452","article-title":"Upadacitinib for the treatment of alopecia areata and severe atopic dermatitis in a paediatric patient: A case report.","volume":"10","author":"Bourkas","year":"2022","journal-title":"SAGE Open Med Case Rep"},{"issue":"4","key":"doi260034r20","doi-asserted-by":"publisher","DOI":"10.1111\/dth.15346","article-title":"Upadacitinib improved alopecia areata in a patient with atopic dermatitis: a case report.","volume":"35","author":"Cantelli","year":"2022","journal-title":"Dermatol Ther"},{"issue":"1S","key":"doi260034r21","doi-asserted-by":"publisher","first-page":"e85","DOI":"10.1097\/DER.0000000000000780","article-title":"Dual efficacy of upadacitinib in 2 patients with concomitant severe atopic dermatitis and alopecia areata.","volume":"32","author":"Gambardella","year":"2021","journal-title":"Dermatitis"},{"issue":"10","key":"doi260034r22","doi-asserted-by":"publisher","first-page":"2749","DOI":"10.1007\/s13555-025-01517-9","article-title":"Evaluating current and emergent JAK inhibitors for alopecia areata: a narrative review.","volume":"15","author":"Sanchez","year":"2025","journal-title":"Dermatol Ther (Heidelb)"},{"issue":"12","key":"doi260034r23","doi-asserted-by":"publisher","first-page":"1285","DOI":"10.1001\/jamadermatol.2025.3537","article-title":"Successful treatment of alopecia areata with one JAK Inhibitor after failure of other JAK inhibitors.","volume":"161","author":"Kalil","year":"2025","journal-title":"JAMA Dermatol"},{"key":"doi260034r24","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1186\/s41927-018-0031-x","article-title":"In vitro and in vivo characterization of the JAK1 selectivity of upadacitinib (ABT-494).","volume":"2","author":"Parmentier","year":"2018","journal-title":"BMC Rheumatol"},{"issue":"18","key":"doi260034r25","doi-asserted-by":"publisher","first-page":"1687","DOI":"10.1056\/NEJMoa2110343","article-title":"Two phase 3 trials of baricitinib for alopecia areata.","volume":"386","author":"King","year":"2022","journal-title":"N Engl J Med"},{"issue":"10387","key":"doi260034r26","doi-asserted-by":"publisher","first-page":"1518","DOI":"10.1016\/S0140-6736(23)00222-2","article-title":"Efficacy and safety of ritlecitinib in adults and adolescents with alopecia areata: a randomised, double-blind, multicentre, phase 2b-3 trial.","volume":"401","author":"King","year":"2023","journal-title":"Lancet"},{"issue":"5","key":"doi260034r27","doi-asserted-by":"publisher","first-page":"880","DOI":"10.1016\/j.jaad.2024.06.097","article-title":"Efficacy and safety of deuruxolitinib, an oral selective Janus kinase inhibitor, in adults with alopecia areata: results from the Phase 3 randomized, controlled trial (THRIVE-AA1).","volume":"91","author":"King","year":"2024","journal-title":"J Am Acad Dermatol"},{"issue":"22","key":"doi260034r29","doi-asserted-by":"publisher","first-page":"1998","DOI":"10.1001\/jama.2025.4347","article-title":"CONSORT 2025 statement: updated guideline for reporting randomized trials.","volume":"333","author":"Hopewell","year":"2025","journal-title":"JAMA"},{"issue":"3","key":"doi260034r30","doi-asserted-by":"publisher","first-page":"440","DOI":"10.1016\/j.jaad.2003.09.032","article-title":"Alopecia areata investigational assessment guidelines\u2013Part II.","volume":"51","author":"Olsen","year":"2004","journal-title":"J Am Acad Dermatol"},{"issue":"5","key":"doi260034r31","doi-asserted-by":"publisher","first-page":"725","DOI":"10.1007\/s40257-020-00545-9","article-title":"Development of clinician-reported outcome (ClinRO) and patient-reported outcome (PRO) measures for eyebrow, eyelash and nail assessment in alopecia areata.","volume":"21","author":"Wyrwich","year":"2020","journal-title":"Am J Clin Dermatol"},{"issue":"1","key":"doi260034r32","doi-asserted-by":"publisher","DOI":"10.1080\/09546634.2025.2460577","article-title":"Patient-reported outcome improvements following scalp hair regrowth among patients with alopecia areata: analysis of the ALLEGRO-2b\/3 trial.","volume":"36","author":"Law","year":"2025","journal-title":"J Dermatolog Treat"},{"issue":"4","key":"doi260034r33","doi-asserted-by":"publisher","first-page":"702","DOI":"10.1111\/bjd.18883","article-title":"The Alopecia Areata Investigator Global Assessment scale: a measure for evaluating clinically meaningful success in clinical trials.","volume":"183","author":"Wyrwich","year":"2020","journal-title":"Br J Dermatol"},{"issue":"10","key":"doi260034r34","doi-asserted-by":"publisher","first-page":"5215","DOI":"10.1007\/s12325-025-03328-y","article-title":"Safety profile of upadacitinib: descriptive analysis in over 27,000 patient-years across rheumatoid arthritis, psoriatic arthritis, axial spondyloarthritis, atopic dermatitis, and inflammatory bowel disease.","volume":"42","author":"Burmester","year":"2025","journal-title":"Adv Ther"},{"key":"doi260034r28","unstructured":"AbbVie Inc. Rinvoq (updacitinib) package insert. Accessed on July 10, 2026. https:\/\/www.rxabbvie.com\/pdf\/rinvoq_pi.pdf"}],"container-title":["JAMA Dermatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/jamanetwork.com\/journals\/jamadermatology\/articlepdf\/2852906\/jamadermatology_mostaghimi_2026_oi_260034_1792511072.87353.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T15:00:45Z","timestamp":1792594845000},"score":1,"resource":{"primary":{"URL":"https:\/\/jamanetwork.com\/journals\/jamadermatology\/fullarticle\/2852906"}},"subtitle":["Two Phase 3 UP-AA Randomized Clinical Trials"],"short-title":[],"issued":{"date-parts":[[2026,10,1]]},"references-count":34,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2026,10,1]]}},"URL":"https:\/\/doi.org\/10.1001\/jamadermatol.2026.2853","relation":{},"ISSN":["2168-6068"],"issn-type":[{"value":"2168-6068","type":"print"}],"subject":[],"published":{"date-parts":[[2026,10,1]]}}}