日本京都大学Kenji Kabashima团队研究了奈莫利珠单抗联合外用制剂治疗特应性皮炎伴瘙痒的疗效。2020年7月9日，该研究发表在《新英格兰医学杂志》上。

奈莫利珠单抗是一种皮下注射的抗白细胞介素-31受体A的人源化单克隆抗体，可治疗特应性皮炎的瘙痒和炎症。在临床2期的研究中，奈莫利珠单抗减轻了特应性皮炎的严重程度。

在一项为期16周、双盲、临床3期的试验中，研究组在日本招募患有特应性皮炎、中度至重度瘙痒、对局部药物反应不足的患者，将其按2：1随机分组，其中143名患者接受皮下奈莫利珠单抗治疗，72名接受安慰剂治疗，每4周1次，直至16周，同时进行局部用药。主要终点是从基线到16周瘙痒症的视觉模拟量表（VAS）评分的百分比变化，分数越高越严重。

基线时两组瘙痒的VAS中位评分为75分。在第16周，奈莫利珠单抗组的VAS评分平均降低了42.8％，安慰剂组平均降低了21.4％，差异显著。奈莫利珠单抗组的湿疹面积和严重程度指数（EASI）评分平均降低了45.9%，安慰剂组平均降低了33.2%。奈莫利珠单抗组中皮肤病生活质量指数（DLQI）4分及以下和失眠严重度指数（ISI）7分及以下的患者分别占40%和55%，安慰剂组则分别占22%和21%。奈莫利珠单抗组注射相关反应的发生率为8%，安慰剂组为3%。

总之，皮下使用奈莫利珠单抗联合局部用药治疗特应性皮炎，与安慰剂加局部用药相比，可进一步减少瘙痒，但注射部分反应的发生率高于安慰剂。

附：英文原文

Title: Trial of Nemolizumab and Topical Agents for Atopic Dermatitis with Pruritus

Author: Kenji Kabashima, M.D., Ph.D.,, Takayo Matsumura, M.S.,, Hiroshi Komazaki, M.S.,, and Makoto Kawashima, M.D., Ph.D.

Issue&Volume: 2020-07-08

Abstract: Abstract

Background

Nemolizumab is a subcutaneously administered humanized monoclonal antibody against interleukin-31 receptor A, which is involved in pruritus and inflammation in atopic dermatitis. In phase 2 studies, nemolizumab lessened the severity of atopic dermatitis.

Methods

In a 16-week, double-blind, phase 3 trial, we randomly assigned Japanese patients with atopic dermatitis and moderate-to-severe pruritus and an inadequate response to topical agents in a 2:1 ratio to receive subcutaneous nemolizumab (60 mg) or placebo every 4 weeks until week 16, with concomitant topical agents. The primary end point was the mean percent change in the visual-analogue scale (VAS) score for pruritus (range, 0 to 100, with higher scores indicating worse pruritus) from baseline to week 16. Secondary end points included the time course of change in the VAS score for pruritus up to week 4, the change in the Eczema Area and Severity Index (EASI) score (range, 0 to 72, with higher scores indicating greater severity), a score of 4 or less on the Dermatology Life Quality Index (DLQI; range, 0 to 30, with higher scores indicating a greater effect on daily life), a score of 7 or less on the Insomnia Severity Index (ISI; range, 0 to 28, with higher scores indicating greater severity), and safety.

Results

A total of 143 patients were randomly assigned to receive nemolizumab and 72 to receive placebo. The median VAS score for pruritus at baseline was 75. At week 16, the mean percent change in the VAS score was 42.8% in the nemolizumab group and 21.4% in the placebo group (difference, 21.5 percentage points; 95% confidence interval, 30.2 to 12.7; P<0.001). The mean percent change in the EASI score was 45.9% with nemolizumab and 33.2% with placebo. The percentage of patients with a DLQI score of 4 or less was 40% in the nemolizumab group and 22% in the placebo group; the percentage of patients with an ISI score of 7 or less was 55% and 21%, respectively. The incidence of injection-related reactions was 8% with nemolizumab and 3% with placebo.

Conclusions

In this 16-week trial, the use of subcutaneous nemolizumab in addition to topical agents for atopic dermatitis resulted in a greater reduction in pruritus than placebo plus topical agents. The incidence of injection-site reactions was greater with nemolizumab than with placebo. Longer and larger trials are necessary to determine whether nemolizumab has a durable effect and is safe for atopic dermatitis.

DOI: 10.1056/NEJMoa1917006

Source: https://www.nejm.org/doi/full/10.1056/NEJMoa1917006