Department of Dermatology, Tohoku University Graduate School of Medicine, Tohoku University Hospital, 1-1 Seiryo-cho, Aoba-ku, Sendai, Miyagi, 980-8574, Japan.
Department of Dermatology, The Jikei University School of Medicine, Tokyo, Japan.
Br J Dermatol. 2017 Mar;176(3):741-751. doi: 10.1111/bjd.14702. Epub 2016 Oct 2.
A T-helper (Th) cell subset Th17 preferentially produces interleukin (IL)-17 and plays a pivotal role in the pathogenesis of psoriasis. However, the pathological roles of IL-17 cascades in generalized pustular psoriasis (GPP) and psoriatic erythroderma (PsE) have not been well established.
To evaluate the efficacy and safety of brodalumab, a human immunoglobulin G2 monoclonal antibody against human IL-17-receptor A (IL-17RA), in Japanese patients with GPP and PsE.
This was an open-label, multicentre, long-term phase III study in Japanese patients with rare and severe types of psoriasis. Patients received brodalumab 140 mg at day 1 and weeks 1 and 2, and then every 2 weeks until week 52. The primary endpoint was the Clinical Global Impression of Improvement (CGI). Safety evaluations included treatment-emergent adverse events (AEs) and changes in laboratory parameters.
A total of 12 patients with GPP and 18 with PsE were enrolled. Ten patients with GPP and 16 with PsE completed the study. At week 52 (last observation carried forward), CGI remission or improvement was achieved in 11 patients with GPP and 18 with PsE. The most commonly reported AE was nasopharyngitis (33·3%). Five serious AEs occurred during the study. However, none was considered treatment-related.
Brodalumab significantly improved the symptoms of patients with GPP and PsE throughout the 52 weeks, and demonstrated favourable safety profiles without any new safety signals. Inhibition of IL-17RA-mediated signalling by brodalumab is expected to be a promising new treatment option for patients with GPP and PsE.
辅助性 T 细胞（Th）亚群 Th17 优先产生白细胞介素（IL）-17，并在银屑病的发病机制中发挥关键作用。然而，IL-17 级联在泛发性脓疱型银屑病（GPP）和银屑病红皮病（PsE）中的病理作用尚未得到充分证实。
评估靶向人白细胞介素-17 受体 A（IL-17RA）的人免疫球蛋白 G2 单克隆抗体布罗达卢单抗在日本 GPP 和 PsE 患者中的疗效和安全性。
这是一项针对日本罕见且严重类型银屑病患者的开放标签、多中心、长期 III 期研究。患者在第 1 天和第 1、2 周接受布罗达卢单抗 140mg，然后每 2 周给药一次，直至第 52 周。主要终点为临床总体印象改善（CGI）。安全性评估包括治疗出现的不良事件（AE）和实验室参数变化。
共纳入 12 例 GPP 患者和 18 例 PsE 患者。10 例 GPP 患者和 16 例 PsE 患者完成了研究。在第 52 周（末次观察结转）时，11 例 GPP 患者和 18 例 PsE 患者达到 CGI 缓解或改善。最常见的报告 AE 是鼻咽炎（33.3%）。研究期间发生了 5 例严重 AE，但均认为与治疗无关。
布罗达卢单抗在 52 周内显著改善了 GPP 和 PsE 患者的症状，并表现出良好的安全性特征，没有新的安全性信号。布罗达卢单抗抑制 IL-17RA 介导的信号转导有望成为 GPP 和 PsE 患者的一种有前途的新治疗选择。
