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

Alan D Irvine¹, Vimal H Prajapati^{2

3

4

5

6

7}, Emma Guttman-Yassky⁸, Eric L Simpson⁹, Kim A Papp^{10

11}, Andrew Blauvelt¹², Chia-Yu Chu¹³, H Chih-Ho Hong^{14

15}, Linda F Stein Gold¹⁶, Marjolein de Bruin-Weller¹⁷, Thomas Bieber^{18

19}, Kenji Kabashima²⁰, David Rosmarin²¹, Cristina Sancho²², Brian M Calimlim²², Ayman Grada²², Yang Yang²², Xiaoqiang Wu²², Gweneth Levy²², Eliza M Raymundo²², Henrique D Teixeira²², Jonathan I Silverberg²³

Affiliations

¹ Clinical Medicine, Trinity College Dublin, Dermatology, Children's Health Ireland at Crumlin, Dublin 12, Ireland. irvinea@tcd.ie.
² Division of Dermatology, Department of Medicine, University of Calgary, Calgary, AB, Canada.
³ Section of Community Pediatrics, Department of Pediatrics, University of Calgary, Calgary, AB, Canada.
⁴ Section of Pediatric Rheumatology, Department of Pediatrics, University of Calgary, Calgary, AB, Canada.
⁵ Dermatology Research Institute, Calgary, AB, Canada.
⁶ Skin Health & Wellness Centre, Calgary, AB, Canada.
⁷ Probity Medical Research, Calgary, AB, Canada.
⁸ 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.
⁹ Department of Dermatology, Oregon Health and Science University, Portland, OR, USA.
¹⁰ Probity Medical Research and Alliance Clinical Trials, Waterloo, ON, Canada.
¹¹ Division of Dermatology, Temerty Faculty of Medicine, University of Toronto, Toronto, ON, Canada.
¹² Blauvelt Consulting, LLC, Annapolis, MD, USA.
¹³ Department of Dermatology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.
¹⁴ Department of Dermatology and Skin Science, University of British Columbia, Vancouver, BC, Canada.
¹⁵ Probity Medical Research, Surrey, BC, Canada.
¹⁶ Dermatology Clinical Research, Henry Ford Health System, Detroit, MI, USA.
¹⁷ National Expertise Center of Atopic Dermatitis, Department of Dermatology and Allergology, University Medical Center Utrecht, Utrecht, The Netherlands.
¹⁸ Christine Kühne-Center for Allergy Research and Education, Medicine Campus, Davos, Switzerland.
¹⁹ Department of Dermatology, University Hospital, Zurich, Switzerland.
²⁰ Department of Dermatology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
²¹ Department of Dermatology, Indiana University School of Medicine, Indianapolis, IN, USA.
²² AbbVie Inc., North Chicago, IL, USA.
²³ Department of Dermatology, The George Washington University School of Medicine and Health Sciences, Washington, DC, USA.

PMID: 40900410
DOI: 10.1007/s40257-025-00975-3

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

Alan D Irvine et al. Am J Clin Dermatol. 2025.

. 2025 Sep 3.

doi: 10.1007/s40257-025-00975-3. Online ahead of print.

Authors

Affiliations

¹ Clinical Medicine, Trinity College Dublin, Dermatology, Children's Health Ireland at Crumlin, Dublin 12, Ireland. irvinea@tcd.ie.
² Division of Dermatology, Department of Medicine, University of Calgary, Calgary, AB, Canada.
³ Section of Community Pediatrics, Department of Pediatrics, University of Calgary, Calgary, AB, Canada.
⁴ Section of Pediatric Rheumatology, Department of Pediatrics, University of Calgary, Calgary, AB, Canada.
⁵ Dermatology Research Institute, Calgary, AB, Canada.
⁶ Skin Health & Wellness Centre, Calgary, AB, Canada.
⁷ Probity Medical Research, Calgary, AB, Canada.
⁸ 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.
⁹ Department of Dermatology, Oregon Health and Science University, Portland, OR, USA.
¹⁰ Probity Medical Research and Alliance Clinical Trials, Waterloo, ON, Canada.
¹¹ Division of Dermatology, Temerty Faculty of Medicine, University of Toronto, Toronto, ON, Canada.
¹² Blauvelt Consulting, LLC, Annapolis, MD, USA.
¹³ Department of Dermatology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.
¹⁴ Department of Dermatology and Skin Science, University of British Columbia, Vancouver, BC, Canada.
¹⁵ Probity Medical Research, Surrey, BC, Canada.
¹⁶ Dermatology Clinical Research, Henry Ford Health System, Detroit, MI, USA.
¹⁷ National Expertise Center of Atopic Dermatitis, Department of Dermatology and Allergology, University Medical Center Utrecht, Utrecht, The Netherlands.
¹⁸ Christine Kühne-Center for Allergy Research and Education, Medicine Campus, Davos, Switzerland.
¹⁹ Department of Dermatology, University Hospital, Zurich, Switzerland.
²⁰ Department of Dermatology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
²¹ Department of Dermatology, Indiana University School of Medicine, Indianapolis, IN, USA.
²² AbbVie Inc., North Chicago, IL, USA.
²³ Department of Dermatology, The George Washington University School of Medicine and Health Sciences, Washington, DC, USA.

PMID: 40900410
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 ).

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Conflict of interest statement

Declarations. Funding: This study was funded by AbbVie Inc. (North Chicago, IL, USA). Data availability: AbbVie is committed to responsible data sharing regarding the clinical trials we sponsor. This includes access to anonymized individual and trial-level data (analysis data sets), as well as other information (e.g., protocols, clinical study reports, or analysis plans), as long as the trials are not part of an ongoing or planned regulatory submission. This includes requests for clinical trial data for unlicensed products and indications. These clinical trial data can be requested by any qualified researchers who engage in rigorous, independent scientific research, and will be provided following review and approval of a research proposal, Statistical Analysis Plan, and execution of a Data Sharing Agreement. Data requests can be submitted at any time after approval in the United States and Europe and after acceptance of this manuscript for publication. The data will be accessible for 12 months, with possible extensions considered. For more information on the process or to submit a request, visit the following link: https://vivli.org/ourmember/abbvie/ then select “Home.” Author contributions: Concept and design: Alan D. Irvine, Emma Guttman-Yassky, Eric L. Simpson, Kim A. Papp, Thomas Bieber, Brian M. Calimlim, Henrique D. Teixeira, and Jonathan I. Silverberg. Data acquisition: Alan D. Irvine, Vimal H. Prajapati, Emma Guttman-Yassky, Eric L. Simpson, Kim A. Papp, Andrew Blauvelt, Chia-Yu Chu, H. Chih-ho Hong, Linda F. Stein Gold, Marjolein de Bruin-Weller, Thomas Bieber, Kenji Kabashima, David Rosmarin, and Jonathan I. Silverberg. Statistical analysis: Brian M. Calimlim, Yang Yang, Xiaoqiang Wu, and Henrique D. Teixeira. Data interpretation: Alan D. Irvine, Vimal H. Prajapati, Emma Guttman-Yassky, Eric L. Simpson, Kim A. Papp, Andrew Blauvelt, H. Chih-ho Hong, Marjolein de Bruin-Weller, Thomas Bieber, Kenji Kabashima, Cristina Sancho, Brian M. Calimlim, Ayman Grada, Yang Yang, Xiaoqiang Wu, Gweneth Levy, Eliza M. Raymundo, Henrique D. Teixeira, and Jonathan I. Silverberg. All authors critically reviewed the manuscript and provided their final approval for publication. Competing interests: ADI has served as a speaker and/or consultant for AbbVie, Alexion, Almirall, Apollo, Arena, Dermavant, Galderma, Janssen, LEO Pharma, Lilly, Novartis, Pfizer, Regeneron, Sanofi, Sitryx, and UCB. VHP has served as an advisor, consultant, and/or speaker for AbbVie, Actelion, Amgen, Apogee Therapeutics, Aralez, Arcutis, Aspen, Bausch Health, BioJAMP/JAMP Pharma, BioScript Solutions, Boehringer Ingelheim, Bristol Myers Squibb, Canadian Psoriasis Network, Celgene, Celltrion, Cipher, CorEvitas, Eczema Society of Canada, Galderma, GlaxoSmithKline, Homeocan, Incyte, J&J Innovative Medicine, Janssen, Johnson & Johnson, LEO Pharma, Lilly, Medexus, Novartis, Organon, Pediapharm, Pfizer, Regeneron, Sanofi Genzyme, Sun Pharma, Tribute, and UCB. He has served as an investigator for AbbVie, AnaptysBio, Apogee Therapeutics, Arcutis, Arena, Asana, Bausch Health, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Concert, CorEvitas, Dermavant, Dermira, Galderma, Incyte, Janssen, LEO Pharma, Lilly, Meiji Pharma, Nektar Therapeutics, Nimbus Lakshmi, Novartis, Pfizer, RAPT Therapeutics, Regeneron, Reistone, Sanofi Genzyme, Sun Pharma, Takeda, UCB, and Vyne Therapeutics. He has received grants from AbbVie, Bausch Health, Janssen, LEO Pharma, Novartis, and Sanofi Genzyme. EG-Y is an employee of Mount Sinai and has received research grants (paid to the institution) from AbbVie, Aclaris, Amgen, AnaptysBio, Apollo, Arcutis, Bristol Meyers Squibb, Concerto Biosciences, Galderma, GSK, Incyte, Inmagene, LEO, Lilly, Opsidio, Pfizer, Q32 Bio, Regeneron, Sanofi, and Xencor. She is also a consultant for AbbVie, Aclaris, Almirall, Alumis, Amgen, AnaptysBio, Apogee, Apollo, Arcutis, Artax Biopharma, Astria, Boehringer Ingelheim, Bristol Meyers Squibb, Celldex, Centrexion, Connect Biopharm, Coty, DBV, Dualitas, Enveda Biosciences, Escient, Galderma, Gate Bio, GSK Immunology, Incyte, Inmagene, Janssen Biotech, Jasper, Kymera, Kyowa Kirin, LEO Pharma, Lilly, Matchpoint, Merck, Nektar, NUMAB, OTSUKA, Pfizer, Pharmaxis, Proteologix, RAPT, RayThera, Regeneron, Ribon, Sanofi, SATO, Schrödinger, Sitryx, Sun Pharma, Takeda, Teva, TRex Bio, UCB, and VRG. ELS has received personal fees from AbbVie, Amgen, Arcutis, Astria, Castle, CorEvitas, Dermira, FIDE, Impetus Healthcare, Incyte, Innovaderm Reche, Janssen, LEO Pharma, Lilly, Numab, Pfizer, Recludix, Regeneron, Roche, Sanofi-Genzyme, and Sitryx, and has received grants from and/or served as a principal investigator for AbbVie, Acrotech, Amgen, Arcutis, Aslan, Castle, Dermavant, CorEvitas, Dermira, Incyte, Lilly, Pfizer, Regeneron, Sanofi-Genzyme, Target, and VeriSkin. KAP has received honoraria and/or grants from AbbVie, Acelyrin, Akros, Alumis, Amgen, Arcutis, Bausch Health/Valeant, Boehringer Ingelheim, Bristol Myers Squibb, Can-Fite Biopharma, Celltrion, Concert Pharmaceuticals, Dermavant, Dermira, DiCE Pharmaceuticals, DiCE Therapeutics, Evelo Biosciences, Forbion, Galderma, Horizon Therapeutics, Incyte, Janssen, Kymab, Kyowa Hakko Kirin, LEO Pharma, Lilly, Meiji Seika Pharma, Mitsubishi Pharma, Nimbus Therapeutics, Novartis, Pfizer, Reistone, Sanofi-Aventis/Genzyme, Sandoz, Sun Pharma, Takeda, Tarsus Pharmaceuticals, UCB, and Zai Lab. AB has served as a speaker (received honoraria) for Lilly and UCB and has served as a scientific adviser (received honoraria) for AbbVie, Almirall, Alumis, Amgen, Anaptysbio, Apogee, Arcutis, Boehringer Ingelheim, Bristol Myers Squibb, Dermavant, and Company, Galderma, GlaxoSmithKline, Incyte, IQVIA, Janssen, LEO Pharma, Lilly Lipidio, Merck, Novartis, Oruka, Paragon, Pfizer, Regeneron, Sanofi, Spherix Global Insights, Sun Pharma, Takeda, UCB, and Union. He has acted as a clinical study investigator (institution has received clinical study funds) for AbbVie, Acelyrin, Almirall, Alumis, Amgen, Arcutis, Boehringer Ingelheim, Bristol Myers Squibb, Dermavant, Galderma, Incyte, Janssen, LEO Pharma, Lilly, Merck, Novartis, Pfizer, Regeneron, Sanofi, Sun Pharma, Takeda, and UCB, and owns stock in Lipidio and Oruka. C-YC has served as an investigator, consultant, speaker, and/or advisory board member for AbbVie, Amgen, Dermira, Janssen, Lilly, Mylan, Novartis, Oneness Biotech, Pfizer, Regeneron, Roche, Sanofi, and Viatris. HCH has served as a consultant, advisory board member, and/or speaker for AbbVie, Amgen, Bausch Health, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Cutanea, Dermira, Dermavant, DS Biopharma, Galderma, GlaxoSmithKline, Incyte, Janssen, LEO Pharma, Lilly, MedImmune, Merck, Mirimar, Novartis, Pfizer, Regeneron, Roche, Sanofi-Genzyme, Sun Pharma, and UCB. He has received research grants for investigator services from AbbVie, Akros, Amgen, Arcutis, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Cutanea, Dermira, Dermavant, DS Biopharma, Evelo, Galderma, GlaxoSmithKline, Incyte, Janssen, LEO Pharma, Lilly, Medimmune, Novartis, Pfizer, Regeneron/Sanofi, Roche, and UCB. LFSG has served as an investigator, speaker, and/or advisor for AbbVie, Amgen, AnaptysBio, Arcutis, Arena, ASLAN, Bausch Health, Boehringer Ingelheim, BMS, Celgene, Coherus, Dermira, Dermavant, Galderma, Incyte, Janssen, LEO Pharma, Lilly, Novartis, Pfizer, Regeneron, Sanofi-Genzyme, Sun Pharma, and UCB. MdeB-W has served as a consultant, advisory board member, and/or speaker for AbbVie, Almirall, Amgen, Aslan, Galderma, LEO Pharma, Lilly, Pfizer, Regeneron, Sanofi, and Takeda. TB has served as a speaker, consultant, and/or investigator for AbbVie, Affibody, Almirall, Amagma, AnaptysBio, Anergis, AOBiom, Apogee, Arena, Aristea, Artax, Asana Biosciences, ASLAN, Astria, Attovia, BambusTx, Bayer Health, Biofilm control, BioVerSys, Boehringer Ingelheim, Bristol Myers Squibb, BYOME Labs, Connect Pharma, Daiichi Sankyo, Dermavant, DICE, Domain, DS Pharma, EQRx, Galderma, Galapagos, Glenmark, GlaxoSmithKline, Incyte, Innovaderm, Janssen, Kirin, Kymab, LEO Pharma, LG Chem, Lilly, L´Oréal, MSD, Medac, Micreos, Nektar, Nextech, Novartis, Numab, OM-Pharma, Ornavi, Overtone, Pfizer, Pierre Fabre, Q32bio, RAPT, Samsung Bioepis, Sanofi/Regeneron, TIRmed, UCB, Union, UPStream Bio, and Yuhan. He is founder and chairman of the board of the nonprofit biotech Davos Biosciences AG within the international Kühne-Foundation and founder of the consulting firm Bieber Dermatology Consulting. KK has received consulting fees, honoraria, grant support, and/or lecturing fees from AbbVie, Amgen, Chugai Pharmaceutical, Kyorin Pharmaceutical, Kyowa Hakko Kirin, Japan Tobacco, LEO Pharma, Lilly Japan, Maruho, Mitsubishi Tanabe, Ono Pharmaceutical, Pola Pharma, Procter & Gamble, Sanofi, Taiho, Tanabe Mitsubishi, and Torii Pharmaceutical. DR has consulted, spoken for, or conducted trials for AbbVie, Abcuro, Almirall, AltruBio, Amgen, Arena, Astria, Boehringer Ingelheim, Bristol Meyers Squibb, Celgene, Concert, CSL Behring, Dermavant, Dermira, Dualitas, EMD Serono, Galderma, Incyte, Janssen, Kymera, Kyowa Kirin, Lilly, Merck, Nektar, Novartis, Pfizer, RAPT, Regeneron, Recludix, Revolo Biotherapeutics, Sanofi, Sun Pharma, UCB, VielaBio, and Zura Bio. CS, BMC, AG, YY, XW, GL, and HDT are full-time employees of AbbVie, and may hold AbbVie stock, stock options, and/or patents. EMR is a former employee of AbbVie, and may hold AbbVie stock, stock options, and/or patents. JIS has received consulting fees from and/or served as an investigator for AbbVie, Anacor, Celgene, GlaxoSmithKline, Lilly, MedImmune, P&G, Pfizer, Regeneron, and Roche. Ethics approval: The study was conducted in accordance with the protocol, International Council for Harmonisation guidelines, and applicable regulations, guidelines, and ethical principles originating from the Declaration of Helsinki. The study protocol was reviewed and approved by a central institutional review board (Advarra, Inc.; registered with the Office for Human Research Protections and the United States Food and Drug Administration under IRB#00000971). The Advarra approval numbers for each study are as follows: Measure Up 1, Pro00034417; Measure Up 2, Pro00034418; AD UP, Pro00034416. Consent to participate: All patients provided written informed consent before screening or undergoing study-specific procedures. Consent to publish: Not applicable. Code availability: Not applicable.

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

Affiliations

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

Authors

Affiliations

Abstract

Conflict of interest statement

References

Associated data

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