Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, NY.
Institute and Comprehensive Center Inflammation Medicine, University of Lübeck, Lübeck, Germany.
J Allergy Clin Immunol. 2020 Mar;145(3):877-884. doi: 10.1016/j.jaci.2019.11.025. Epub 2019 Nov 29.
Atopic dermatitis is a chronic inflammatory skin disease characterized by pruritic skin lesions.
We sought to evaluate the safety and efficacy of multiple doses of the selective Janus kinase 1 inhibitor upadacitinib in patients with moderate to severe atopic dermatitis.
In the 16-week, double-blind, placebo-controlled, parallel-group, dose-ranging portion of this 88-week trial in 8 countries (ClinicalTrials.gov, NCT02925117; ongoing, not recruiting), adults with moderate to severe disease and inadequate control by topical treatment were randomized 1:1:1:1, using an interactive response system and stratified geographically, to once-daily upadacitinib oral monotherapy 7.5, 15, or 30 mg or placebo. The primary end point was percentage improvement in Eczema Area and Severity Index from baseline at week 16. Efficacy was analyzed by intention-to-treat in all randomized patients. Safety was analyzed in all randomized patients who received study medication, based on actual treatment.
Patients (N = 167) enrolled from November 21, 2016, to April 20, 2017. All were randomized and analyzed for efficacy (each upadacitinib group, n = 42; placebo, n = 41); 166 were analyzed for safety (each upadacitinib group, n = 42; placebo, n = 40). The mean (SE) primary efficacy end point was 39% (6.2%), 62% (6.1%), and 74% (6.1%) for the upadacitinib 7.5-, 15-, and 30-mg groups, respectively, versus 23% (6.4%) for placebo (P = .03, <.001, and <.001). Serious adverse events occurred in 4.8% (2 of 42), 2.4% (1 of 42), and 0% (0 of 42) of upadacitinib groups (vs 2.5% [1 of 40] for placebo).
A dose-response relationship was observed for upadacitinib efficacy; the 30-mg once-daily dose showed the greatest clinical benefit. Dose-limiting toxicity was not observed.
特应性皮炎是一种慢性炎症性皮肤病，其特征为瘙痒性皮损。
我们旨在评估多种剂量选择性 Janus 激酶 1 抑制剂 upadacitinib 治疗中重度特应性皮炎患者的安全性和疗效。
在这项 88 周、8 个国家进行的、双盲、安慰剂对照、平行分组、剂量范围的试验的 16 周、双盲、安慰剂对照、平行分组、剂量范围部分（ClinicalTrials.gov，NCT02925117；正在进行，不招募）中，中重度疾病且局部治疗控制不足的成年人按 1:1:1:1 比例随机分配，使用交互式反应系统并按地理分层，接受每日一次 upadacitinib 口服单药治疗 7.5、15 或 30 mg 或安慰剂。主要终点为第 16 周时 Eczema Area and Severity Index 自基线的改善百分比。所有随机患者均按意向治疗进行疗效分析。基于实际治疗，所有接受研究药物的随机患者均进行安全性分析。
2016 年 11 月 21 日至 2017 年 4 月 20 日，共招募了 167 名患者。所有患者均被随机分组并进行疗效分析（每组 upadacitinib 组 n=42；安慰剂组 n=41）；166 名患者进行安全性分析（每组 upadacitinib 组 n=42；安慰剂组 n=40）。主要疗效终点的平均（SE）为 39%（6.2%）、62%（6.1%）和 74%（6.1%），分别为 upadacitinib 7.5、15 和 30 mg 组，而安慰剂组为 23%（6.4%）（P=0.03，<.001，<.001）。upadacitinib 组各有 4.8%（2 例）、2.4%（1 例）和 0%（0 例）的患者发生严重不良事件（vs 安慰剂组 2.5%[1 例]）。
观察到 upadacitinib 疗效存在剂量反应关系；每日一次 30mg 剂量显示出最大的临床获益。未观察到剂量限制毒性。
