Department of Dermatology, Nippon Medical School, Tokyo, Japan.
Department of Dermatology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Br J Dermatol. 2017 Aug;177(2):419-427. doi: 10.1111/bjd.15493. Epub 2017 Jun 27.
Ustekinumab, a fully human monoclonal antibody against interleukin-12/23, may potentially be effective for severe atopic dermatitis (AD) treatment.
To evaluate efficacy and safety of ustekinumab 45 mg and 90 mg in patients with severe AD.
In this randomized, placebo-controlled, phase II study, Japanese patients (aged 20-65 years) with severe or very severe AD entered a 12-week double-blind treatment period during which they received (1 : 1 : 1) ustekinumab 45 mg, 90 mg or placebo subcutaneous injections at weeks 0 and 4, with follow-up until week 24. The primary efficacy end point was percentage change from baseline in Eczema Area and Severity Index (EASI) score at week 12. Major secondary efficacy end points included the proportion of patients achieving EASI 50, EASI 75, Investigator's Global Assessment score 0-1, change from baseline Atopic Dermatitis Itch Scale and Dermatology Life Quality Index.
A total of 79 patients were randomized [ustekinumab 45 mg (n = 24), 90 mg (n = 28), placebo (n = 27)]. Ustekinumab treatment showed nonsignificant improvement in least square mean change from baseline EASI score at week 12 [45 mg: -38·2%, 95% confidence interval (CI) -21·02-19·51; P < 0·94 and 90 mg: -39·8%, 95% CI -21·84-17·14; P < 0·81] vs. placebo (-37·5%). A nonsignificant improvement in major secondary efficacy end points was observed in both ustekinumab groups vs. placebo. The most common treatment-emergent adverse events were nasopharyngitis and worsened AD (higher in placebo vs. ustekinumab groups).
Ustekinumab 45 mg and 90 mg did not demonstrate meaningful efficacy in Japanese patients with severe AD. The treatment was generally well tolerated.
乌司奴单抗是一种针对白细胞介素-12/23 的全人源单克隆抗体，可能对重度特应性皮炎（AD）的治疗有效。
评估乌司奴单抗 45 mg 和 90 mg 治疗重度 AD 患者的疗效和安全性。
这是一项随机、安慰剂对照、II 期研究，日本 20-65 岁的重度或极重度 AD 患者入组，进入为期 12 周的双盲治疗期，在第 0 周和第 4 周接受乌司奴单抗 45 mg、90 mg 或安慰剂皮下注射，随访至第 24 周。主要疗效终点为第 12 周时湿疹面积和严重程度指数（EASI）评分较基线的变化百分比。主要次要疗效终点包括达到 EASI 50、EASI 75、研究者总体评估（IGA）评分 0-1、基线时特应性皮炎瘙痒量表和皮肤病生活质量指数（DLQI）的变化。
共有 79 例患者被随机分组[乌司奴单抗 45 mg（n=24）、90 mg（n=28）、安慰剂（n=27）]。乌司奴单抗治疗第 12 周时 EASI 评分较基线的最小二乘均数变化无显著改善[45 mg：-38.2%，95%置信区间（CI）-21.02-19.51；P＜0.94 和 90 mg：-39.8%，95%CI-21.84-17.14；P＜0.81]，安慰剂组为-37.5%。乌司奴单抗两组与安慰剂组相比，次要疗效终点均有改善，但无统计学意义。最常见的治疗期间出现的不良事件是鼻咽炎和 AD 加重（安慰剂组高于乌司奴单抗组）。
乌司奴单抗 45 mg 和 90 mg 对日本重度 AD 患者无明显疗效。治疗总体耐受性良好。
