Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Randomized Controlled Trial
. 2023 May 1;159(5):526-535.
doi: 10.1001/jamadermatol.2023.0391.

Efficacy and Safety of Upadacitinib Treatment in Adolescents With Moderate-to-Severe Atopic Dermatitis: Analysis of the Measure Up 1, Measure Up 2, and AD Up Randomized Clinical Trials

Amy S Paller  1 , Barry Ladizinski  2 , Pedro Mendes-Bastos  3 , Elaine Siegfried  4 , Weily Soong  5 , Vimal H Prajapati  6   7 , Peter Lio  8 , Jacob P Thyssen  9 , Eric L Simpson  10 , Andrew M Platt  2 , Eliza M Raymundo  2 , Jianzhong Liu  2 , Brian M Calimlim  2 , Xiaohong Huang  2 , Yihua Gu  2 , Xiaofei Hu  2 , Yang Yang  2 , John C Su  11 , Min Zheng  12 , Kiwako Yamamoto-Hanada  13 , Henrique D Teixeira  2 , Alan D Irvine  14
Affiliations
Randomized Controlled Trial

Efficacy and Safety of Upadacitinib Treatment in Adolescents With Moderate-to-Severe Atopic Dermatitis: Analysis of the Measure Up 1, Measure Up 2, and AD Up Randomized Clinical Trials

Amy S Paller et al. JAMA Dermatol. .

Erratum in

Abstract

Importance: Atopic dermatitis onset usually occurs in childhood. Persistence of disease into adolescence and adulthood is common. It is important to evaluate new treatment options in adolescents because of the high unmet need in this population.

Objective: To assess the efficacy and safety of upadacitinib to treat moderate-to-severe atopic dermatitis in adolescents.

Design, setting, and participants: Prespecified analysis of adolescents enrolled in 3 randomized, double-blind, placebo-controlled phase 3 clinical trials in more than 20 countries across Europe, North and South America, Oceania, the Middle East, and the Asia-Pacific region from July 2018 through December 2020. Participants were adolescents aged 12 to 17 years with moderate-to-severe atopic dermatitis. Data analysis was performed from April to August 2021.

Interventions: Patients were randomized (1:1:1) to once-daily oral upadacitinib 15 mg, upadacitinib 30 mg, or placebo alone (Measure Up 1 and Measure Up 2) or with topical corticosteroids (AD Up).

Main outcomes and measures: Safety and efficacy, including at least a 75% improvement in the Eczema Area and Severity Index from baseline and validated Investigator Global Assessment for Atopic Dermatitis score of 0 (clear) or 1 (almost clear) at week 16 (coprimary end points).

Results: A total of 552 adolescents (290 female; 262 male) were randomized. Mean (SD) age was 15.4 (1.8), 15.5 (1.7), and 15.3 (1.8) years for adolescents in Measure Up 1, Measure Up 2, and AD Up, respectively. In Measure Up 1, Measure Up 2, and AD Up, respectively, a greater proportion of adolescents (% [95% CI]) achieved at least 75% improvement in the Eczema Area and Severity Index at week 16 with upadacitinib 15 mg (73% [63%-84%], 69% [57%-81%], 63% [51%-76%]), and upadacitinib 30 mg (78% [68%-88%], 73% [62%-85%], 84% [75%-94%]), than with placebo (12% [4%-20%], 13% [5%-22%], 30% [19%-42%]; nominal P < .001 for all comparisons vs placebo). Similarly, a greater proportion of adolescents treated with upadacitinib achieved a validated Investigator Global Assessment for Atopic Dermatitis score of 0 or 1 at week 16 and improvements in quality of life with upadacitinib than with placebo. Upadacitinib was generally well tolerated in adolescents. Acne was the most common adverse event, and all acne events were mild or moderate.

Conclusions and relevance: In this analysis of 3 randomized clinical trials, upadacitinib was an effective treatment for adolescents with moderate-to-severe atopic dermatitis, with an acceptable safety profile.

Trial registration: ClinicalTrials.gov Identifiers: NCT03569293 (Measure Up 1), NCT03607422 (Measure Up 2), and NCT03568318 (AD Up).

PubMed Disclaimer

Conflict of interest statement

Conflict of Interest Disclosures: Dr Paller reported personal fees and grants from AbbVie during the conduct of the study; grants from AnaptysBio, Dermavant, Incyte, Janssen, and Regeneron and personal fees from 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 Ladizinski reported being an employee of AbbVie. Dr Mendes-Bastos reported nonfinancial support (medical writing) from AbbVie during the conduct of the study; and personal fees from AbbVie, Janssen, Novartis, LEO Pharma, Almirall, Sanofi, Viatris, Cantabria Labs, L’Oréal, Eli Lilly, Pfizer, Pierre Fabre, and Organon and nonfinancial support from Novartis outside the submitted work. Dr Siegfried reported other (consulting contract, no fees paid) from AbbVie outside the submitted work; and AI Therapeutics (contracted research), ASLAN Pharmaceuticals (consultant fees), Boehringer Ingelheim (consulting fees), Incyte (consulting fees), Regeneron (consulting fees, honoraria; fees to SSM/SLU related to sponsoring clinical trials), Sanofi Genzyme (consulting fees, honoraria), UCB (data safety monitoring board [DSMB], consulting fees), Verrica (consulting fees, honoraria; fees to SSM/SLU related to sponsoring a clinical trial), LEO Pharma (consulting fees, DSMB), Novan (consulting fees; DSMB), Novartis (consulting fees), Pfizer (consulting fee; DSMB; grant funding to support 2020-2022 Peds Derm Fellow), Pierre Fabre (consulting fee; fees to SSM/SLU related to sponsoring a clinical trial), Janssen (PI, fees to SSM/SLU related to sponsoring a clinical trial), and Eli Lilly (fees to SSM/SLU related to sponsoring a clinical trial). Dr Soong reported grants, personal fees, and nonfinancial support from AbbVie during the conduct of the study; grants and personal fees from Regeneron, Sanofi, LEO Pharma, Pfizer, Eli Lilly, Amgen, Genentech, and Novartis and grants from Incyte and ASLAN outside the submitted work. Dr Prajapati reported grants and personal fees from AbbVie, Bausch Health, Celgene, LEO Pharma, Novartis, and Sanofi Genzyme; grants from Janssen; and personal fees from Amgen, Arcutis, Arena, Asana, Boehringer Ingelheim, Bristol Myers Squibb, Concert, Dermavant, Dermira, Eli Lilly, Galderma, GlaxoSmithKline, Homeocan, Incyte, Janssen, L’Oréal, Medexus, Nimbus Lakshmi, Pediapharm, Pfizer, Regeneron, Reistone, Sun Pharma, UCB, and Corrona/CorEvitas outside the submitted work. Dr Lio reported personal fees from AbbVie, Pfizer, Regeneron/Sanofi, Eli Lilly, LEO Pharma, Incyte, AOBiome, Galderma, L’Oréal, Bristol Myers Squibb, Almirall, ASLAN Pharma, and Dermavant outside the submitted work; in addition, Dr Lio had a patent for Theraplex AIM pending. Dr Thyssen reported grants from Sanofi Genzyme, Regeneron, and Pfizer and personal fees from LEO Pharma, Eli Lilly, Aslan Pharmaceuticals, Arena Pharmaceuticals, OM, Almirall, and AbbVie during the conduct of the study; and personal fees from Coloplast outside the submitted work. Dr Simpson reported grants and personal fees from AbbVie during the conduct of the study; grants from AbbVie, Amgen, Arcutis, Aslan, Castle Biosciences, CorEvitas, Dermavant, Dermira, Eli Lilly, Incyte, Kymab, Kyowa Kirin, National Jewish Health, LEO Pharma, Pfizer, Regeneron, Sanofi, and Target RWE and personal fees from Advances in Cosmetic Medical Derm Hawaii LLC, AbbVie, Amgen, AOBiome LLC, Arcutis Biotherapeutics, Arena Pharmaceuticals, Aslan Pharma, Boehringer Ingelheim USA, Boston Consulting Group, Bristol Myers Squibb, Collective Acumen, LLC, CorEvitas, Dermira, Eli Lilly, Evelo Biosciences, Evidera, Excerpta Medica, FIDE, Galderma, Gesellschaft Z, GlaxoSmithKline, Incyte, Janssen, Johnson & Johnson, LEO Pharma, Medscape LLC, Merck, Maui Derm, MLG Operating, MJH Holding, Pfizer, Physicians World LLC, PRImE, Regeneron, Revolutionizing Atopic Dermatitis, Roivant, Sanofi Genzyme, Trevi Therapeutics, Valeant, Vindico Medical Education, and WebMD outside the submitted work. Dr Platt reported personal fees from AbbVie (employment and stock) during the conduct of the study and outside the submitted work. Dr Raymundo reported employment and stock from AbbVie during the conduct of the study. Dr Liu reported employment from AbbVie during the conduct of the study and outside the submitted work. Dr Calimlim reported employment from AbbVie and may hold AbbVie stock or stock options during the conduct of the study. Dr Huang reported employment from AbbVie during the conduct of the study. Dr Gu reported employment from AbbVie and may hold stocks during the conduct of the study. Dr Yang reported employment from AbbVie during the conduct of the study and outside the submitted work. Dr Su reported other from AbbVie as investigator during the conduct of the study; other from Bristol Myers Squibb as investigator, grants from Bioderma, grants from Ego Pharmaceuticals, other from Eli Lilly as investigator, grants from Janssen, other from Mayne as investigator, grants from Novartis, grants from Pfizer as investigator, grants from Pierre Fabre, and other from Sanofi as investigator outside the submitted work. Dr Yamamoto-Hanada reports personal fees from AbbVie during the conduct of the study; grants from Takano Medical and Natural Science and personal fees from AbbVie, Pfizer, Otsuka, Maruho, Torii, Kao, and BCASE outside the submitted work. Dr Teixeira reported employment from AbbVie and holding AbbVie stock during the conduct of the study. Dr Irvine reported personal fees from AbbVie during the conduct of the study; personal fees from Pfizer, LEO Pharma, Sanofi/RGN, Almirall, and Eli Lilly outside the submitted work. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Proportion of Adolescents Achieving EASI 75 Response Over the Double-blind Period
A, Measure Up 1. B, Measure Up 2. C, AD Up. Nominal P values are calculated using Cochran-Mantel-Haenszel test with the adjustment of baseline vIGA-AD categories (3; 4). Based on nonresponder imputation incorporating multiple imputation to handle missing data due to COVID-19 or nonresponder imputation only if there were no missing data due to COVID-19. EASI 75 indicates at least a 75% reduction in Eczema Area and Severity Index; TCS, topical corticosteroids; UPA, upadacitinib; vIGA-AD, validated Investigator Global Assessment for Atopic Dermatitis. aP = .03. bP = .006. cP < .001. dP = .001. eP = .002.
Figure 2.
Figure 2.. Proportion of Adolescents Achieving vIGA-AD Response 0/1 Over the Double-blind Period
A, Measure Up 1. B, Measure Up 2. C, AD Up. Nominal P values are calculated using Cochran-Mantel-Haenszel test with the adjustment of baseline vIGA-AD categories (3; 4). Based on nonresponder imputation incorporating multiple imputation to handle missing data due to COVID-19 or nonresponder imputation only if there were no missing data due to COVID-19. TCS indicates topical corticosteroids; UPA, upadacitinib; vIGA-AD, validated Investigator Global Assessment for Atopic Dermatitis. aP = .001. bP < .001. cP = .004. dP = .007.
See this image and copyright information in PMC

Comment in

References

    1. Langan SM, Irvine AD, Weidinger S. Atopic dermatitis. Lancet. 2020;396(10247):345-360. doi:10.1016/S0140-6736(20)31286-1 - DOI - PubMed
    1. Weidinger S, Beck LA, Bieber T, Kabashima K, Irvine AD. Atopic dermatitis. Nat Rev Dis Primers. 2018;4(1):1. doi:10.1038/s41572-018-0001-z - DOI - PubMed
    1. Bylund S, Kobyletzki LB, Svalstedt M, Svensson Å. Prevalence and incidence of atopic dermatitis: a systematic review. Acta Derm Venereol. 2020;100(12):adv00160. doi:10.2340/00015555-3510 - DOI - PMC - PubMed
    1. Silverberg JI, Barbarot S, Gadkari A, et al. . Atopic dermatitis in the pediatric population: a cross-sectional, international epidemiologic study. Ann Allergy Asthma Immunol. 2021;126(4):417-428.e2. doi:10.1016/j.anai.2020.12.020 - DOI - PubMed
    1. Drucker AM. Atopic dermatitis: burden of illness, quality of life, and associated complications. Allergy Asthma Proc. 2017;38(1):3-8. doi:10.2500/aap.2017.38.4005 - DOI - PubMed

Publication types

Associated data