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Clinical Trial
. 2024 Dec 1;160(12):1304-1313.
doi: 10.1001/jamadermatol.2024.3696.

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

Amy S Paller  1   2 , Pedro Mendes-Bastos  3 , Elaine Siegfried  4 , Lawrence F Eichenfield  5   6   7 , Weily Soong  8 , Vimal H Prajapati  9   10   11   12   13   14 , Peter Lio  15 , Eric L Simpson  16 , Eliza M Raymundo  17 , Smitha Suravaram  17 , Xiaofei Hu  17 , Yang Yang  17 , Xiaohong Huang  17 , Brian M Calimlim  17 , Andrew M Platt  17 , John C Su  18   19 , Min Zheng  20 , Kiwako Yamamoto-Hanada  21 , Henrique D Teixeira  17 , Alan D Irvine  22
Affiliations
Clinical Trial

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

Amy S Paller et al. JAMA Dermatol. .

Abstract

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.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Paller reported grants from AbbVie during the conduct of the study as well as grants from AnaptysBio, Dermavant, Incyte, Janssen, and Regeneron and personal fees from AbbVie, Almirall, Arena, Asana, Bausch, BiomX, Boehringer Ingelheim, Catawba, Forte Pharma, Galderma, InMed Pharmaceuticals, Leo Pharma, Novartis, Pfizer, RAPT Therapeutics, Sanofi, and Seanergy outside the submitted work. Dr Mendes-Bastos reported personal fees from AbbVie, Novartis, Pfizer, Janssen, Eli Lilly, Sanofi, Regeneron, L’Orea, Pierre Fabre, Viatris, Organon, Evelo Bioscience, and CS Labs as well as consultant fees from AbbVie, Pfizer, Janssen-Cilag, Leo Pharma, Novartis, Eli Lilly, Sanofi, L’Oreal, Pierre Fabre, Viatris, Organon, Evelo Biosciences, and CS Labs outside the submitted work; and is a principal investigator in clinical trials for AbbVie, Amgen, Biogen, Janssen, Pfizer, Novartis, and Sanofi. Dr Siegfried reported personal fees from AI Therapeutcs, Aslan, Cara, Eli Lilly, Esperare, Incyte, Janssen, Leo Pharma, Novan, Novartis, Pfizer, Pierre Fabre, RAPT Therapeutics, UCB, Verrica, and Dermavant outside the submitted work. Dr Eichenfield reported funding from AbbVie to his institution during the conduct of the study; personal fees from AbbVie, Attovia, Apogee, Bristol Meyers Squib, Janssen, Leo Pharma, Regeneron, and UCB as well as funding from Amgen, Arcutis, Bausch, Castle Biosci, Dermavant, Galderma, Incyte, Lilly, Pfizer, and Sanofi paid to his institution; and is on the Board of Directors of and owns options in Forte outside the submitted work. Dr Soong reported grants, personal fees, and nonfinancial support from AbbVie during the conduct of the study; grants and personal fees from Pfizer, Regeneron, Sanofi, Dermavant, Incyte, UCB, Amgen, Leo Pharma, and Eli Lilly; and grants from Allakos, Galderma, and Escent outside the submitted work. Dr Prajapati reported personal fees from AbbVie, Amgen, AnaptysBio, Apogee Therapeutics, Arcutis, Arena, Asana, Bausch Health, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Concert, CorEvitas, Celltrion, Dermavant, Dermira, Eli Lilly, Galderma, Incyte, Janssen/Johnson & Johnson Innovative Medicine, Leo Pharma, Meiji Pharma, Nektar Therapeutics, Nimbus Lakshmi, JAMP Pharma, Novartis, Organon, Pfizer, RAPT Therapeutics, Regeneron, Sanofi Genzyme, Sun Pharma, and UCB outside the submitted work. Dr Lio reported personal fees from AbbVie, Galderma, Sanofi Genzyme/Regeneron, Eli Lilly, Incyte, La Roche-Posay/L'Oreal, Pfizer, Pierre Fabre Dermatologie, and Arcutis during the conduct of the study; personal fees from ASLAN, Bristol Myers Squibb, Castle Biosci, Dermavant, Leo Pharma, Micreos, UCB, Unilever, and Verrica; stock options from Alphyn Biologics and Concerto Biosci outside the submitted work; has a patent for Theraplex AIM pending; and is a board member for the National Eczema Association. Dr Simpson reported grants and personal fees from AbbVie during the conduct of the study; personal fees from AbbVie, Amgen, Arcutis, Areteia Therapeutics, Bristol Myers Squibb, CorEvitas, Corvus, Dermira, Eli Lilly, Evelo Biosciences, FIDE, Forte Bio RX, Galderma, GlaxoSmithKline, Gilead Sciences, Impetus Healthcare, Incyte, Innovaderm Reche, Janssen, Johnson & Johnson, Kyowa Kirin Pharmaceutical Development, Leo Pharma, Merck, MJH, NUMAB Therapeutics AG, Pfizer, Physicians World LLC, PRImE, Recludix Pharma, Regeneron, Roivant, Sanofi-Genzyme, SITRYX Therapeutics, Trevi Therapeutics, and Valeant and grants from AbbVie, Acrotech, Amgen, Arcutis, ASLAN, Castle, CorEvitas, Dermavant, Dermira, Incyte, Lilly, Kymab, Kyowa Kirin, National Jewish Health, Leo Pharma, Pfizer, Regeneron, Sanofi, Target, and VeriSkin outside the submitted work; and his spouse is a subinvestigator for AbbVie, Allakos, Amgen, Arcutis, Aslan, Bristol Myers Squibb, Dermavant, DermBiont, Eli Lilly, Galderma, Hallux, Incyte, Leo Pharma, Moberg, Technoderma, and UCB. Dr Su reported funding from AbbVie paid to his institution during the conduct of the study as well as funding from Amgen, ASLAN, Bristol Myers Squibb, Eli Lilly, Galderma, Janssen, Leo Pharma, Novartis, Pierre Fabre, Pfizer, and Sanofi paid to his institution outside the submitted work. Dr Yamamoto-Hanada reported grants from Kao, Alcare, Natural Science, and Takano as well as personal fees from Torii, Otsuka, Sanofi, Pfizer, AbbVie, Bcase, Pierre Fabre Japan, Takano, Kao, and Maruho outside the submitted work. Dr Irvine reported personal fees from AbbVie during the conduct of the study; personal fees from Pfizer, Eli Lilly, Sanofi/Regeneron, and Almirall outside the submitted work; and has a patent for Regeneron/Sanofi pending. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Proportion of Adolescents Achieving EASI-75, EASI-90, and EASI-100 Across 76 Weeks
Analyses were conducted in the intention-to-treat population using the observed case approach. EASI indicates Eczema Area and Severity Index; TCS, topical corticosteroids. Error bars indicate 95% CIs.
Figure 2.
Figure 2.. Proportion of Adolescents Achieving Validated Investigator Global Assessment for Atopic Dermatitis Score of 0 or 1 Over 76 Weeks
Analyses were conducted in the intention-to-treat population using the observed case approach. NA indicates not applicable; TCS, topical corticosteroids. Error bars indicate 95% CIs.
Figure 3.
Figure 3.. Proportion of Adolescents Achieving Worst Pruritus Numerical Rating Scale Improvement of 4 Points or More Across 76 Weeks
Analyses were conducted in the intention-to-treat population using the observed case approach. NA indicates not applicable; TCS, topical corticosteroids. Error bars indicate 95% CIs.
See this image and copyright information in PMC

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