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, <.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). CONCLUSIONS 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.

中文翻译：

---

成人中度至重度特应性皮炎的Upadacitinib：一项随机，安慰剂对照试验的16周结果。

背景技术特应性皮炎是一种慢性炎症性皮肤病，其特征是瘙痒性皮肤损害。目的我们试图评估多剂量选择性Janus激酶1抑制剂upadacitinib在中度至重度特应性皮炎患者中的安全性和有效性。方法在8个国家（ClinicalTrials.gov，NCT02925117；正在进行中，而非招募中）的这项为期88周的试验中，为期16周，双盲，安慰剂对照，平行组，剂量范围的部分，成人为中度至重度使用互动反应系统将疾病和局部治疗控制不当，以1：1：1：1的比例随机分配，并在地理上分层，以每日一次7.5、15或30 mg或安慰剂的upadacitinib口服单药治疗。主要终点是第16周时与基线相比，湿疹面积和严重性指数的百分比改善。通过意向治疗对所有随机患者的疗效进行了分析。根据实际治疗情况，对接受研究药物的所有随机患者的安全性进行了分析。结果从2016年11月21日至2017年4月20日入组患者（N = 167）。所有患者均被随机分组​​并进行疗效分析（每个upadacitinib组，n = 42；安慰剂，n = 41）；分析了166种药物的安全性（每个upadacitinib组，n = 42；安慰剂，n = 40）。Upadacitinib 7.5 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23组安慰剂的百分比（6.4％）（P = .03，<。001和<.001）。Upadacitinib组发生严重不良事件的发生率为4.8％（42个中的2个），2.4％（42个中的1个）和0％（42个中的0个）（安慰剂组为2.5％[40个中的1个]）。结论观察到了upadacitinib疗效的剂量反应关系。每天一次30毫克的剂量显示出最大的临床益处。没有观察到剂量限制的毒性。