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Clinical Trial
. 2025 Jul 1;161(7):688-697.
doi: 10.1001/jamadermatol.2025.0982.

Ivarmacitinib for Moderate to Severe Atopic Dermatitis in Adults and Adolescents: A Phase 3 Randomized Clinical Trial

Yan Zhao  1 , Melinda Gooderham  2 , Bin Yang  3 , Jiyuan Wu  4 , Liming Wu  5 , Wei Jing Loo  6 , Darryl Toth  7 , Maxwell Sauder  8 , Jingyi Li  9 , Aijun Chen  10 , Xiaohua Tao  11 , Jianyun Lu  12 , Zhiqiang Song  13 , Jiande Han  14 , Hongyi Li  15 , Yijing Li  16 , Lihong Xu  17 , Jianzhong Zhang  1
Affiliations
Clinical Trial

Ivarmacitinib for Moderate to Severe Atopic Dermatitis in Adults and Adolescents: A Phase 3 Randomized Clinical Trial

Yan Zhao et al. JAMA Dermatol. .

Abstract

Importance: Ivarmacitinib, a selective oral Janus kinase 1 (JAK1) inhibitor, has demonstrated efficacy for treating adults with moderate to severe atopic dermatitis (AD) in a phase 2 trial.

Objective: To evaluate the efficacy and adverse events of ivarmacitinib in adolescents and adults with moderate to severe AD.

Design, setting, and participants: This multicenter, double-blind, placebo-controlled phase 3 randomized clinical trial included patients aged 12 to 75 years with moderate to severe AD. Patients were enrolled from 53 sites in Canada and China from April 2021 to April 2022. Data were analyzed from July 11 to September 27, 2023.

Interventions: Patients were randomized (1:1:1) to receive once-daily 4- or 8-mg ivarmacitinib or placebo for 16 weeks.

Main outcomes and measures: Co-primary end points were the proportions of patients achieving an Investigator Global Assessment (IGA) score of 0 (clear) or 1 (almost clear) with at least a 2-grade improvement from baseline and an Eczema Area and Severity Index score improvement of 75% (EASI-75) at week 16.

Results: Of 336 randomized patients (mean [SD] age, 31.1 [15.4] years; 213 [63.4%] male; 286 [85.1%] Asian), 113 received 4-mg ivarmacitinib, 112 received 8-mg ivarmacitinib, and 111 received placebo. At week 16, significantly more patients in the 4-mg ivarmacitinib group (41 of 113 [36.3%]; 95% CI, 27.5%-45.9%; P < .001) and the 8-mg ivarmacitinib group (47 of 112 [42.0%]; 95% CI, 32.7%-51.7%; P < .001) achieved an IGA score of 0 or 1 with at least a 2-grade improvement compared to the placebo group (10 of 111 [9.0%]; 95% CI, 4.4%-15.9%). EASI-75 responses were also significantly higher in the ivarmacitinib groups: 61 patients (54.0%; 95% CI, 44.4%-63.4%; P < .001) in the 4-mg group, and 74 (66.1%; 95% CI, 56.5%-74.8%; P < .001) in 8-mg group compared to 24 patients (21.6%; 95% CI, 14.4%-30.4%) in the placebo group. Treatment-emergent adverse events were reported by 78 patients (69.0%) in the 4-mg group, 74 (66.1%) in the 8-mg group, and 72 (64.9%) in the placebo group. Serious treatment-emergent adverse events occurred in 3 patients (2.7%) in the 4-mg group, 2 (1.8%) in the 8-mg group, and 3 (2.7%) in the placebo group.

Conclusions and relevance: This phase 3 randomized clinical trial determined that once-daily ivarmacitinib demonstrated significant efficacy and a favorable risk-benefit profile for treating moderate to severe AD in adults and adolescents. These results support the potential of ivarmacitinib as a new therapeutic option.

Trial registration: ClinicalTrials.gov Identifier: NCT04875169.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Gooderham reported nonfinancial support from Reistone during the conduct of the study; speaking, advisory, and/or research fees from AbbVie, Amgen, Incyte, Apogee, Dermira, Eli Lilly, Galderma, Pfizer, Aslan, Union, Arcutis, Dermavant, Nektar, Regeneron, Sanofi, all outside the submitted work. Dr Toth reported research support and advisory fees from AbbVie, Amgen, Arcutis, Avillion, Bausch Health Care, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Dermavant, Dow Pharmaceuticals, Galderma, Incyte, Janssen, Leo Pharma, Lilly, Merck, Novartis, Pfizer, Regeneron/Sanofi, Sun Pharma, Takeda, and UCB, all outside the submitted work. Dr Sauder reported research funding/personal fees from Amgen, AbbVie, Arcutis, Bausch Health, Bristol Myers Squibb, Eli Lilly, Galderma, Incyte Pharma, Janssen, L’Oreal Canada, LEO Pharma, Merck, Novartis, Pfizer, Regeneron, Sanofi, Sun Pharmaceuticals, UCB Canada, Probity, Alumis, Amgen, AbbVie, Bristol Myers Squibb, Galderma, Incyte, Janssen, Nektar, Pfizer, Sanofi, and Takeda; equity in Johnson & Johnson and Merck; serving as a treasurer for the Canadian Dermatology Association, Ontario secretary for the Dermatology Association, and medical adviser to the Canadian Association of Psoriasis Patients; and support/consulting fees from the Academy for Continued Advancement in Health Education, Canadian Collaborative Research Network, Master Clinical Alliance, Oncology Education, PeerVoice, Polaris Health, Bicom, Catalytic Health, Master Clinical Alliance, MedPlan Communications, RBC Consultants, Fusion MD, and University of Toronto, all outside the submitted work. No other disclosures were reported.

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References

    1. Narla S, Silverberg JI. Association between atopic dermatitis and autoimmune disorders in US adults and children: a cross-sectional study. J Am Acad Dermatol. 2019;80(2):382-389. doi: 10.1016/j.jaad.2018.09.025 - DOI - PubMed
    1. Silverberg JI. Comorbidities and the impact of atopic dermatitis. Ann Allergy Asthma Immunol. 2019;123(2):144-151. doi: 10.1016/j.anai.2019.04.020 - 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. Faye O, Flohr C, Kabashima K, et al. Atopic dermatitis: A global health perspective. J Eur Acad Dermatol Venereol. 2024;38(5):801-811. - PubMed
    1. Chiesa Fuxench ZC, Block JK, Boguniewicz M, et al. Atopic Dermatitis in America Study: a cross-sectional study examining the prevalence and disease burden of atopic dermatitis in the US adult population. J Invest Dermatol. 2019;139(3):583-590. doi: 10.1016/j.jid.2018.08.028 - DOI - PubMed

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