Upadacitinib in adults with moderate to severe atopic dermatitis: 16-week results from a randomized, placebo-controlled trial
Upadacitinib in adults with moderate to severe atopic dermatitis: 16-week results from a randomized, placebo-controlled trial
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DOI：
10.1016/j.jaci.2019.11.025
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发表时间：
2020-03-01
影响因子：
14.2
通讯作者：
Silverberg, Jonathan I.
中科院分区：
文献类型：
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作者：
Guttman-Yassky, Emma;Thaci, Diamant;Silverberg, Jonathan I.
背景：特应性皮炎是一种以瘙痒性皮肤病变为特征的慢性炎症性皮肤病。目的：我们试图评估多剂量选择性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有效性。方法：在这项为期88周的试验中，在8个国家进行了为期16周的双盲、安慰剂对照、平行组、剂量范围部分（ClinicalTrials.gov, NCT02925117；正在进行中，未招募），患有中度至重度疾病且局部治疗控制不足的成年人被随机分为1:1:1:1:1，使用互动反应系统和地理分层，每天一次的upadacitinib口服单药治疗7.5、15或30 mg或安慰剂。主要终点是第16周湿疹面积和严重程度指数较基线改善的百分比。通过意向治疗分析所有随机患者的疗效。在实际治疗的基础上，对所有接受研究药物的随机患者进行安全性分析。结果：患者（N = 167）于2016年11月21日至2017年4月20日入组。所有患者随机化并分析疗效（每个upadacitinib组，n = 42；安慰剂组，n = 41）；166例进行安全性分析（每个upadacitinib组，n = 42；安慰剂组，n = 40）。upadacitini7.5 mg、15 mg和30 mg组的平均（SE）主要疗效终点分别为39%（6.2%）、62%（6.1%）和74%(6.1%)，而安慰剂组为23% (6.4%)(P = 0.03；
Background: Atopic dermatitis is a chronic inflammatory skin disease characterized by pruritic skin lesions.Objective: 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.Methods: 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.Results: 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,