Upadacitinib in Adolescents With Moderate to Severe Atopic Dermatitis: Analysis of 3 Phase 3 Randomized Clinical Trials Through 76 Weeks.

Autor:	Paller AS; Department of Dermatology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois.; Department of Pediatrics, Feinberg School of Medicine, Northwestern University, Chicago, Illinois., Mendes-Bastos P; Dermatology Center, Hospital CUF Descobertas, Lisboa, Portugal., Siegfried E; Department of Pediatrics, St Louis University School of Medicine, St Louis, Missouri., Eichenfield LF; Division of Pediatric and Adolescent Dermatology, Rady Children's Hospital, San Diego, California.; Department of Dermatology, UC San Diego School of Medicine, University of California, San Diego.; Department of Pediatrics, UC San Diego School of Medicine, University of California, San Diego., Soong W; AllerVie Health-Alabama Allergy & Asthma Center and Clinical Research Center of Alabama, Birmingham., Prajapati VH; Division of Dermatology, Department of Medicine, University of Calgary, Calgary, Alberta, Canada.; Section of Community Pediatrics, Department of Pediatrics, University of Calgary, Calgary, Alberta, Canada.; Section of Pediatric Rheumatology, Department of Pediatrics, University of Calgary, Calgary, Alberta, Canada.; Skin Health & Wellness Centre, Calgary, Alberta, Canada.; Dermatology Research Institute, Calgary, Alberta, Canada.; Probity Medical Research, Calgary, Alberta, Canada., Lio P; Medical Dermatology Associates of Chicago, Chicago, Illinois., Simpson EL; Department of Dermatology, Oregon Health & Science University, Portland., Raymundo EM; AbbVie Inc, North Chicago, Illinois., Suravaram S; AbbVie Inc, North Chicago, Illinois., Hu X; AbbVie Inc, North Chicago, Illinois., Yang Y; AbbVie Inc, North Chicago, Illinois., Huang X; AbbVie Inc, North Chicago, Illinois., Calimlim BM; AbbVie Inc, North Chicago, Illinois., Platt AM; AbbVie Inc, North Chicago, Illinois., Su JC; Department of Dermatology, Monash University, Melbourne, Australia.; Eastern Health and MCRI, University of Melbourne, Melbourne, Australia., Zheng M; Department of Dermatology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China., Yamamoto-Hanada K; Allergy Center, National Center for Child Health and Development, Tokyo, Japan., Teixeira HD; AbbVie Inc, North Chicago, Illinois., Irvine AD; Clinical Medicine, Trinity College Dublin, Dublin, Ireland.
Jazyk:	angličtina
Zdroj:	JAMA dermatology [JAMA Dermatol] 2024 Oct 23. Date of Electronic Publication: 2024 Oct 23.
DOI:	10.1001/jamadermatol.2024.3696
Abstrakt:	Importance: The Measure Up 1, Measure Up 2, and AD Up studies demonstrated the efficacy and adverse events of upadacitinib through 52 weeks in adults and adolescents with atopic dermatitis (AD); however, longer-term outcomes (longer than 1 year) in adolescents have not previously been available. Objective: To evaluate the efficacy and adverse events of upadacitinib in adolescent patients with moderate to severe AD through 76 weeks. Design, Setting, and Participants: The Measure Up 1, Measure Up 2, and AD Up trials are ongoing double-blind, placebo-controlled phase 3 randomized clinical trials including adolescents (aged 12 to 17 years) with moderate to severe AD. Data were collected from August 2018 to April 2022, and data were analyzed from June 2022 to September 2023. Interventions: Adolescents were randomized 1:1:1 to receive once-daily oral upadacitinib, 15 mg; upadacitinib, 30 mg; or placebo, either alone (Measure Up 1 and Measure Up 2 trials) or with topical corticosteroids (AD Up). At week 16, placebo-treated patients were rerandomized to receive upadacitinib, 15 mg, or upadacitinib, 30 mg, daily. Main Outcomes and Measures: Coprimary end points assessing efficacy included achievement of 75% reduction or more in the Eczema Area and Severity Index Score (EASI-75) from baseline, Validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD) score of clear (0) or almost clear (1) with 2 grades or more of improvement, and Worst Pruritus Numerical Rating Scale (WP-NRS) improvement of 4 points or greater through week 76 for participants with a WP-NRS score of 4 points or higher at baseline. Results: From all studies, 542 adolescents were included; of these, 284 (52.4%) were female. At week 76, among patients in the Measure Up 1, Measure Up 2, and AD Up trials, EASI-75 was achieved by 89.1%, 84.4%, and 87.8% of adolescents taking upadacitinib, 15 mg, respectively, and by 96.1%, 93.6%, and 82.7% of adolescents taking upadacitinib, 30 mg, indicating maintenance or improvement of EASI-75 across 76 weeks with upadacitinib. Efficacy measured by achievement of vIGA-AD score of 0 or 1 and WP-NRS improvement of 4 points or more from baseline was similarly maintained or improved through week 76 for adolescents taking upadacitinib, 15 mg or 30 mg. Long-term outcomes in Measure Up 1, Measure Up 2, and AD Up participants were consistent with the known adverse event profile of upadacitinib (herpetic infection: 4.0, 1.9, and 1.1 events per 100 patient-years, respectively; creatine kinase elevation: 11.6, 11.0, and 7.1 events per 100 patient-years); no new signals were observed with either dose. Conclusions and Relevance: In this study assessing 3 randomized clinical trials, long-term treatment of adolescents with moderate to severe AD with upadacitinib demonstrated a favorable benefit-risk profile, with sustained efficacy responses through 76 weeks. Trial Registrations: Measure Up 1 trial: ClinicalTrials.gov Identifier: NCT03569293; Measure Up 2 trial: NCT03607422; AD Up trial: NCT03568318.
Databáze:	MEDLINE
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