Efficacy and Safety of Upadacitinib in Patients With Moderate-to-Severe Atopic Dermatitis: Phase 3 Randomized Clinical Trial Results Through 140 Weeks

Authors

Alan D. Irvine, Clinical Medicine, Trinity College Dublin, Dermatology, Children's Health Ireland at Crumlin, Dublin 12, Ireland. irvinea@tcd.ie.
Vimal H. Prajapati, Division of Dermatology, Department of Medicine, University of Calgary, Calgary, AB, Canada.
Emma Guttman-Yassky, The Kimberly and Eric J. Waldman Department of Dermatology Director, Center of Excellence in Eczema Director, Laboratory of Inflammatory Skin Diseases, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Eric L. Simpson, Department of Dermatology, Oregon Health and Science University, Portland, OR, USA.
Kim A. Papp, Probity Medical Research and Alliance Clinical Trials, Waterloo, ON, Canada.
Andrew Blauvelt, Blauvelt Consulting, LLC, Annapolis, MD, USA.
Chia-Yu Chu, Department of Dermatology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.
H Chih-Ho Hong, Department of Dermatology and Skin Science, University of British Columbia, Vancouver, BC, Canada.
Linda F. Gold, Dermatology Clinical Research, Henry Ford Health System, Detroit, MI, USA.
Marjolein de Bruin-Weller, National Expertise Center of Atopic Dermatitis, Department of Dermatology and Allergology, University Medical Center Utrecht, Utrecht, The Netherlands.
Thomas Bieber, Christine Kühne-Center for Allergy Research and Education, Medicine Campus, Davos, Switzerland.
Kenji Kabashima, Department of Dermatology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
David Rosmarin, Department of Dermatology, Indiana University School of Medicine, Indianapolis, IN, USA.
Cristina Sancho, AbbVie Inc., North Chicago, IL, USA.
Brian M. Calimlim, AbbVie Inc., North Chicago, IL, USA.
Ayman Grada, AbbVie Inc., North Chicago, IL, USA.
Yang Yang, AbbVie Inc., North Chicago, IL, USA.
Xiaoqiang Wu, AbbVie Inc., North Chicago, IL, USA.
Gweneth Levy, AbbVie Inc., North Chicago, IL, USA.
Eliza M. Raymundo, AbbVie Inc., North Chicago, IL, USA.
Henrique D. Teixeira, AbbVie Inc., North Chicago, IL, USA.
Jonathan I. Silverberg, Department of Dermatology, The George Washington University School of Medicine and Health Sciences, Washington, DC, USA.

Document Type

Journal Article

Publication Date

9-3-2025

Journal

American journal of clinical dermatology

DOI

10.1007/s40257-025-00975-3

Abstract

BACKGROUND: Upadacitinib is an oral selective Janus kinase inhibitor approved to treat moderate-to-severe atopic dermatitis (AD) in adults and adolescents; long-term efficacy and safety data beyond 1 year are needed. OBJECTIVE: The aim was to evaluate the long-term efficacy and safety of upadacitinib treatment through 140 weeks in patients with moderate-to-severe AD. METHODS: Measure Up 1 (MeUp1; NCT03569293), Measure Up 2 (MeUp2; NCT03607422), and AD Up (NCT03568318) are ongoing, phase 3, randomized clinical trials evaluating upadacitinib 15 mg (UPA15) and 30 mg (UPA30) in adults and adolescents with moderate-to-severe AD. This interim analysis evaluated efficacy and safety through week 140. At baseline, patients were randomized 1:1:1 to receive once-daily UPA15, UPA30, or placebo alone (MeUp1/2) or with concomitant topical corticosteroids (AD Up). At week 16, patients initially randomized to placebo were rerandomized 1:1 to UPA15 or UPA30. Skin and itch efficacy assessments included achievement of ≥ 75%/≥ 90%/100% improvement from baseline in Eczema Area and Severity Index (EASI 75/90/100), validated Investigator Global Assessment for AD score of clear/almost clear (vIGA-AD 0/1), and ≥ 4-point improvement from baseline in Worst Pruritus Numerical Rating Scale (∆WP-NRS≥4). Safety assessments included incidence of treatment-emergent adverse events. RESULTS: A total of 2782 patients were randomized in MeUp1/2 or AD Up. Efficacy response rates, including optimal outcomes such as EASI 90 and WP-NRS score of 0/1, were sustained through week 140 in all three studies. At week 140, EASI 75 was achieved by 85.5%/90.5% (UPA15/UPA30; integrated MeUp1/2) and 81.5%/90.0% (UPA15/UPA30; AD Up) of patients, and vIGA-AD 0/1 was achieved by 56.6%/64.4% (UPA15/UPA30; integrated MeUp1/2) and 52.0%/56.8% (UPA15/UPA30; AD Up) of patients. Over 60% of patients across all three studies achieved ∆WP-NRS≥4 at week 140. Pooled safety data across all three studies demonstrated safety profiles consistent with 16-week and 52-week analyses. CONCLUSIONS: UPA15 and UPA30 with and without topical corticosteroids demonstrated robust, durable efficacy and a favorable safety profile through 140 weeks in adults and adolescents with moderate-to-severe AD. TRIAL REGISTRATION: Measure Up 1 (NCT03569293; https://clinicaltrials.gov/study/NCT03569293 ), Measure Up 2 (NCT03607422; https://clinicaltrials.gov/study/NCT03607422 ), and AD Up (NCT03568318; https://clinicaltrials.gov/study/NCT03568318 ).

APA Citation

Irvine, Alan D.; Prajapati, Vimal H.; Guttman-Yassky, Emma; Simpson, Eric L.; Papp, Kim A.; Blauvelt, Andrew; Chu, Chia-Yu; Hong, H Chih-Ho; Gold, Linda F.; de Bruin-Weller, Marjolein; Bieber, Thomas; Kabashima, Kenji; Rosmarin, David; Sancho, Cristina; Calimlim, Brian M.; Grada, Ayman; Yang, Yang; Wu, Xiaoqiang; Levy, Gweneth; Raymundo, Eliza M.; Teixeira, Henrique D.; and Silverberg, Jonathan I., "Efficacy and Safety of Upadacitinib in Patients With Moderate-to-Severe Atopic Dermatitis: Phase 3 Randomized Clinical Trial Results Through 140 Weeks" (2025). GW Authored Works. Paper 8003.
https://hsrc.himmelfarb.gwu.edu/gwhpubs/8003

Department

Dermatology