Department of Dermatology, Bispebjerg Hospital, University of Copenhagen, Copenhagen, Denmark.
Institute and Comprehensive Center Inflammation Medicine, University of Lübeck, Lübeck, Germany.
J Eur Acad Dermatol Venereol. 2023 Sep;37(9):1871-1880. doi: 10.1111/jdv.19232. Epub 2023 Jun 21.
Atopic dermatitis (AD) is a heterogeneous inflammatory skin disease with different clinical phenotypes based on factors such as age, race, comorbidities, and clinical signs and symptoms. The effect of these factors on therapeutic responses in AD has only been scarcely studied and not for upadacitinib. Currently, there is no biomarker predicting response to upadacitinib.
Evaluate the efficacy of the oral Janus kinase inhibitor upadacitinib across patient subgroups (baseline demographics, disease characteristics and prior treatment) in patients with moderate-to-severe AD.
Data from phase 3 studies (Measure Up 1, Measure Up 2 and AD Up) were utilized for this post hoc analysis. Adults and adolescents with moderate-to-severe AD were randomized to receive once daily oral upadacitinib 15 mg, upadacitinib 30 mg or placebo; patients enrolled in the AD Up study received concomitant topical corticosteroids. Data from the Measure Up 1 and Measure Up 2 studies were integrated.
A total of 2584 patients were randomized. A consistently greater proportion of patients achieved at least 75% improvement in the Eczema Area and Severity Index, a 0 or 1 on the validated Investigator Global Assessment for Atopic Dermatitis, and improvement in itch (including an achievement of a reduction of ≥4; and score of 0/1 in Worst Pruritus Numerical Rating Scale) with upadacitinib compared with placebo at Week 16, regardless of age, sex, race, body mass index, AD severity, body surface area involvement, history of atopic comorbidities or asthma, or previous exposure to systemic therapy or cyclosporin.
Upadacitinib had consistently high skin clearance rates and itch efficacy across subgroups of patients with moderate-to-severe AD through Week 16. These results support upadacitinib as a suitable treatment option in a variety of patients.
ClinicalTrials.gov Identifiers: NCT03569293 (Measure Up 1), NCT03607422 (Measure Up 2) and NCT03568318 (AD Up).
特应性皮炎（AD）是一种异质性炎症性皮肤疾病，其临床表现型基于年龄、种族、合并症和临床体征及症状等因素而有所不同。这些因素对 AD 治疗反应的影响仅得到了少量研究，而针对乌帕替尼的研究则更少。目前，尚无预测乌帕替尼治疗反应的生物标志物。
评估口服 JAK 抑制剂乌帕替尼在特应性皮炎患者亚组（基线人口统计学、疾病特征和既往治疗）中的疗效。
本事后分析使用了 3 项 III 期研究（Measure Up 1、Measure Up 2 和 AD Up）的数据。中重度 AD 成年和青少年患者被随机分配接受每日一次口服乌帕替尼 15 mg、乌帕替尼 30 mg 或安慰剂治疗；AD Up 研究中的患者同时接受外用皮质类固醇治疗。Measure Up 1 和 Measure Up 2 研究的数据进行了整合。
共纳入 2584 例患者。与安慰剂相比，乌帕替尼治疗组在第 16 周时达到 Eczema Area and Severity Index 至少改善 75%、研究者整体评估（Atopic Dermatitis）得分为 0 或 1、瘙痒改善（包括瘙痒减轻≥4 分，以及最严重瘙痒数字评分量表得分为 0/1）的患者比例始终更高，无论年龄、性别、种族、体重指数、AD 严重程度、体表面积受累、特应性合并症或哮喘病史、或既往接受系统治疗或环孢素治疗。
乌帕替尼在第 16 周时对中重度 AD 患者的亚组始终具有较高的皮肤清除率和止痒疗效。这些结果支持乌帕替尼作为各种患者的一种合适治疗选择。
ClinicalTrials.gov 标识符：NCT03569293（Measure Up 1）、NCT03607422（Measure Up 2）和 NCT03568318（AD Up）。
