Safety and efficacy of erenumab for preventive treatment of chronic migraine: a randomised, double-blind, placebo-controlled phase 2 trial
Safety and efficacy of erenumab for preventive treatment of chronic migraine: a randomised, double-blind, placebo-controlled phase 2 trial
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DOI：
10.1016/s1474-4422(17)30083-2
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发表时间：
2017-06-01
期刊：
影响因子：
48
通讯作者：
Lenz, Robert
中科院分区：
文献类型：
--
作者：
Tepper, Stewart;Ashina, Messoud;Lenz, Robert
背景降钙素基因相关肽（CGRP）途径在偏头痛病理生理学中很重要。我们评估了erenumab（一种抗CGRP受体的全人单克隆抗体）在慢性偏头痛患者中的疗效和安全性。方法这是一项针对18-65岁慢性偏头痛成人的erenumab 2期、随机、双盲、安慰剂对照、多中心研究，招募来自北美和欧洲的69个头痛和临床研究中心。慢性偏头痛定义为每月头痛天数 15 天或以上，其中偏头痛天数或以上为 8 天。患者被随机分配 (3:2:2) 接受皮下注射安慰剂、erenumab 70 mg 或erenumab 140 mg，每 4 周给药一次，持续 12 周。使用交互式语音或网络响应系统集中执行随机化。患者、研究研究者和研究申办者人员对治疗分配情况不知情。主要终点是每月偏头痛天数从基线到双盲治疗最后 4 周（第 9-12 周）的变化。安全性终点是不良事件、临床实验室值、生命体征和抗erenumab抗体。功效分析组包括接受至少一剂研究产品并完成至少一项基线后每月测量的患者。安全性分析组包括接受至少一剂研究产品的患者。该研究已在 ClinicalTrials.gov 注册，编号为 NCT02066415。 结果 从 2014 年 4 月 3 日到 2015 年 12 月 4 日，667 名患者被随机分配接受安慰剂 (n=286)、erenumab 70 mg (n=191) 或erenumab 140 mg (n=190)。与安慰剂相比，Erenumab 70 mg 和 140 mg 减少了每月偏头痛天数（两种剂量均为 -6.6 天，而安慰剂为 -4.2 天；差异 -2.5，95% CI -3.5 至 -1.4，p
Background The calcitonin gene-related peptide (CGRP) pathway is important in migraine pathophysiology. We assessed the efficacy and safety of erenumab, a fully human monoclonal antibody against the CGRP receptor, in patients with chronic migraine.Methods This was a phase 2, randomised, double-blind, placebo-controlled, multicentre study of erenumab for adults aged 18-65 years with chronic migraine, enrolled from 69 headache and clinical research centres in North America and Europe. Chronic migraine was defined as 15 or more headache days per month, of which eight or more were migraine days. Patients were randomly assigned (3: 2: 2) to subcutaneous placebo, erenumab 70 mg, or erenumab 140 mg, given every 4 weeks for 12 weeks. Randomisation was centrally executed using an interactive voice or web response system. Patients, study investigators, and study sponsor personnel were masked to treatment assignment. The primary endpoint was the change in monthly migraine days from baseline to the last 4 weeks of double-blind treatment (weeks 9-12). Safety endpoints were adverse events, clinical laboratory values, vital signs, and antierenumab antibodies. The efficacy analysis set included patients who received at least one dose of investigational product and completed at least one post-baseline monthly measurement. The safety analysis set included patients who received at least one dose of investigational product. The study is registered with ClinicalTrials.gov, number NCT02066415.Findings From April 3, 2014, to Dec 4, 2015, 667 patients were randomly assigned to receive placebo (n=286), erenumab 70 mg (n=191), or erenumab 140 mg (n=190). Erenumab 70 mg and 140 mg reduced monthly migraine days versus placebo (both doses -6.6 days vs placebo -4.2 days; difference -2.5, 95% CI -3.5 to -1.4, p