抗白细胞介素-31 受体 A 抗体治疗特应性皮炎。
Anti-Interleukin-31 Receptor A Antibody for Atopic Dermatitis.
机构信息
From the Department of Dermatology and Allergology, Ludwig Maximilian University, Munich, Germany (T.R., A.W.); the Department of Dermatology, Oregon Health and Science University, Portland (J.M.H.); the Department of Dermatology, Graduate School of Medical Sciences, Kyushu University, Fukuoka (M.F.), Tokyo Teishin Hospital (T.E.) and Chugai Pharmaceutical (R.M., H.Y.), Tokyo, the Department of Dermatology, Kyoto University Graduate School of Medicine, Kyoto (K.K.), and Precursory Research for Embryonic Science and Technology, Japan Science and Technology Agency, Saitama (K.K.) - all in Japan; Jagiellonian University School of Medicine, Krakow (G.P.), Academic Health, Dermatology Clinic, Rzeszow (I.M.), and the Department of Histology and Embryology, Center for Biostructure, Medical University of Warsaw, Warsaw (R.G.) - all in Poland; and Chugai Pharma Europe, London (J.S.).
出版信息
N Engl J Med. 2017 Mar 2;376(9):826-835. doi: 10.1056/NEJMoa1606490.
BACKGROUND
Interleukin-31 may play a role in the pathobiologic mechanism of atopic dermatitis and pruritus. We wanted to assess the efficacy and safety of nemolizumab (CIM331), a humanized antibody against interleukin-31 receptor A, in the treatment of atopic dermatitis.
METHODS
In this phase 2, randomized, double-blind, placebo-controlled, 12-week trial, we assigned adults with moderate-to-severe atopic dermatitis that was inadequately controlled by topical treatments to receive subcutaneous nemolizumab (at a dose of 0.1 mg, 0.5 mg, or 2.0 mg per kilogram of body weight) or placebo every 4 weeks or an exploratory dose of 2.0 mg of nemolizumab per kilogram every 8 weeks. The primary end point was the percentage improvement from baseline in the score on the pruritus visual-analogue scale (on which a negative change indicates improvement) at week 12. Secondary end points included changes in the score on the Eczema Area and Severity Index (EASI, on which a negative change indicates improvement), and body-surface area of atopic dermatitis.
RESULTS
Of 264 patients who underwent randomization, 216 (82%) completed the study. At week 12, among the patients who received nemolizumab every 4 weeks, changes on the pruritus visual-analogue scale were -43.7% in the 0.1-mg group, -59.8% in the 0.5-mg group, and -63.1% in the 2.0-mg group, versus -20.9% in the placebo group (P<0.01 for all comparisons). Changes on the EASI were -23.0%, -42.3%, and -40.9%, respectively, in the nemolizumab groups, versus -26.6% in the placebo group. Respective changes in body-surface area affected by atopic dermatitis were -7.5%, -20.0%, and -19.4% with nemolizumab, versus -15.7% with placebo. Among the patients receiving nemolizumab every 4 weeks, treatment discontinuations occurred in 9 of 53 patients (17%) in the 0.1-mg group, in 9 of 54 (17%) in the 0.5-mg group, and in 7 of 52 (13%) in the 2.0-mg group, versus in 9 of 53 (17%) in the placebo group.
CONCLUSIONS
In this phase 2 trial, nemolizumab at all monthly doses significantly improved pruritus in patients with moderate-to-severe atopic dermatitis, which showed the efficacy of targeting interleukin-31 receptor A. The limited size and length of the trial preclude conclusions regarding adverse events. (Funded by Chugai Pharmaceutical; XCIMA ClinicalTrials.gov number, NCT01986933 .).
背景
白细胞介素-31 可能在特应性皮炎和瘙痒的发病机制中发挥作用。我们希望评估针对白细胞介素-31 受体 A 的人源化抗体 nemolizumab（CIM331）在治疗特应性皮炎中的疗效和安全性。
方法
在这项为期 12 周的 2 期、随机、双盲、安慰剂对照试验中，我们将未通过局部治疗充分控制的中度至重度特应性皮炎的成年患者随机分配至接受每 4 周皮下注射 nemolizumab（剂量为 0.1mg、0.5mg 或 2.0mg/每公斤体重）或安慰剂，或每 8 周接受一次探索性剂量 2.0mg/kg 的 nemolizumab。主要终点是在第 12 周时瘙痒视觉模拟量表（负向变化表示改善）的基线改善百分比。次要终点包括 Eczema Area and Severity Index（EASI，负向变化表示改善）和特应性皮炎体表面积的变化。
结果
在接受随机分组的 264 例患者中，216 例（82%）完成了研究。在每 4 周接受 nemolizumab 的患者中，在瘙痒视觉模拟量表上的变化分别为 0.1mg 组 -43.7%、0.5mg 组 -59.8%、2.0mg 组 -63.1%，安慰剂组 -20.9%（所有比较均<0.01）。EASI 的变化分别为 nemolizumab 组 -23.0%、-42.3%和-40.9%，安慰剂组 -26.6%。特应性皮炎受累体表面积的相应变化分别为 nemolizumab 组 -7.5%、-20.0%和-19.4%，安慰剂组 -15.7%。在每 4 周接受 nemolizumab 的患者中，0.1mg 组有 9 例（17%）、0.5mg 组有 9 例（17%）和 2.0mg 组有 7 例（13%）因治疗中断，安慰剂组有 9 例（17%）。
结论
在这项 2 期试验中，所有每月剂量的 nemolizumab 均显著改善了中度至重度特应性皮炎患者的瘙痒，这表明靶向白细胞介素-31 受体 A 的疗效。试验的规模和长度有限，无法得出关于不良事件的结论。（由 Chugai Pharmaceutical 资助；XCIMA ClinicalTrials.gov 编号，NCT01986933）。
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