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

IF 11.5 1区医学 Q1 DERMATOLOGY

JAMA dermatology Pub Date : 2025-04-30 DOI:10.1001/jamadermatol.2025.0982

Yan Zhao, Melinda Gooderham, Bin Yang, Jiyuan Wu, Liming Wu, Wei Jing Loo, Darryl Toth, Maxwell Sauder, Jingyi Li, Aijun Chen, Xiaohua Tao, Jianyun Lu, Zhiqiang Song, Jiande Han, Hongyi Li, Yijing Li, Lihong Xu, Jianzhong Zhang

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引用次数: 0

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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伊瓦马替尼治疗成人和青少年中至重度特应性皮炎：一项3期随机临床试验

重要性：选择性口服Janus激酶1 （JAK1）抑制剂伊瓦马替尼（Ivarmacitinib）在一项2期试验中显示出治疗中度至重度特应性皮炎（AD）的有效性。目的：评价伊瓦马替尼治疗青少年和成人中重度AD的疗效和不良事件。设计、环境和参与者：这项多中心、双盲、安慰剂对照的3期随机临床试验包括12至75岁的中度至重度AD患者。2021年4月至2022年4月，患者从加拿大和中国的53个地点入组。数据分析时间为2023年7月11日至9月27日。干预措施：患者随机（1:1:1）接受每日一次4或8毫克伊瓦马替尼或安慰剂，为期16周。主要结局和措施：共同主要终点是在第16周达到研究者总体评估（IGA）评分0（明确）或1（几乎明确）且较基线改善至少2级和湿疹面积和严重程度指数评分改善75% （EASI-75）的患者比例。结果：336例随机患者(平均[SD]年龄31.1[15.4]岁；213名（63.4%）男性；286人（85.1%），113人接受4mg伊瓦马替尼治疗，112人接受8mg伊瓦马替尼治疗，111人接受安慰剂治疗。在第16周，4mg伊瓦马替尼组的患者明显更多(113例中有41例[36.3%]；95% ci, 27.5%-45.9%；结论和相关性：这项3期随机临床试验确定，每日一次的伊瓦马替尼在治疗成人和青少年中重度阿尔茨海默病方面表现出显著的疗效和良好的风险-收益特征。这些结果支持伊瓦马替尼作为一种新的治疗选择的潜力。试验注册：ClinicalTrials.gov标识符：NCT04875169。

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来源期刊

JAMA dermatology DERMATOLOGY-

CiteScore

14.10

自引率

5.50%

发文量

300

期刊介绍： JAMA Dermatology is an international peer-reviewed journal that has been in continuous publication since 1882. It began publication by the American Medical Association in 1920 as Archives of Dermatology and Syphilology. The journal publishes material that helps in the development and testing of the effectiveness of diagnosis and treatment in medical and surgical dermatology, pediatric and geriatric dermatology, and oncologic and aesthetic dermatologic surgery. JAMA Dermatology is a member of the JAMA Network, a consortium of peer-reviewed, general medical and specialty publications. It is published online weekly, every Wednesday, and in 12 print/online issues a year. The mission of the journal is to elevate the art and science of health and diseases of skin, hair, nails, and mucous membranes, and their treatment, with the aim of enabling dermatologists to deliver evidence-based, high-value medical and surgical dermatologic care. The journal publishes a broad range of innovative studies and trials that shift research and clinical practice paradigms, expand the understanding of the burden of dermatologic diseases and key outcomes, improve the practice of dermatology, and ensure equitable care to all patients. It also features research and opinion examining ethical, moral, socioeconomic, educational, and political issues relevant to dermatologists, aiming to enable ongoing improvement to the workforce, scope of practice, and the training of future dermatologists. JAMA Dermatology aims to be a leader in developing initiatives to improve diversity, equity, and inclusion within the specialty and within dermatology medical publishing.