用于预防偏头痛的依瑞奈珠单抗的安全性和耐受性：2b 期和 3 期临床试验的汇总分析。

Safety and Tolerability of Fremanezumab for the Prevention of Migraine: A Pooled Analysis of Phases 2b and 3 Clinical Trials.

机构信息

Jefferson Headache Center, Thomas Jefferson University, Philadelphia, PA, USA.

New England Institute for Neurology and Headache, Stamford, CT, USA.

出版信息

Headache. 2019 Jun;59(6):880-890. doi: 10.1111/head.13534. Epub 2019 Apr 12.

DOI:10.1111/head.13534

PMID:30977520

Abstract

OBJECTIVE

Presentation of pooled analysis of safety data for fremanezumab in patients with chronic (CM) or episodic migraine (EM) from 4 placebo-controlled phase 2b and phase 3 studies.

BACKGROUND

There is a need for an effective, safe, and well-tolerated preventive therapy that specifically targets the pathophysiology of migraine to reduce the frequency and severity of migraine attacks in patients with CM or EM who experience 4 or more migraine days per month. Fremanezumab is a fully humanized monoclonal antibody that targets calcitonin gene-related peptide, a neuropeptide involved in the pathophysiology of migraine.

DESIGN/METHODS: The 4 placebo-controlled phases 2b and 3 studies included in this analysis were 16-week, multicenter, randomized, double-blind, placebo-controlled, and parallel-group studies consisting of a screening visit, a 28-day pretreatment baseline period, and a 12-week treatment period with a final evaluation 4 weeks after the final dose of the study drug. Safety endpoints included adverse events (AEs) and immunogenicity.

RESULTS

A total of 2566 patients were randomized across all studies (fremanezumab, n = 1704; placebo, n = 862), and 2563 patients were treated. Common reasons for study discontinuation were withdrawal by patient (n = 78), patient lost to follow-up (n = 60), and AE (n = 50). The mean (standard deviation) duration of exposure was 83.8 (13.6) days for the patients who received fremanezumab, with a total exposure of 390.4 patient years and maximum exposure of 181 days. AEs were mostly mild to moderate in severity and were reported among 48-69% of patients in all treatment groups, and most were injection site reactions (pain, induration, and erythema). Two deaths occurred (chronic obstructive pulmonary disease and intentional overdose of diphenhydramine), both of which were deemed unrelated to study drug by the investigators and sponsor. Cardiovascular adverse events, abnormal liver function tests, and hypersensitivity were uncommon and occurred at similar rates between the placebo and fremanezumab groups.

CONCLUSIONS

Fremanezumab is a generally safe and well-tolerated preventive therapy for migraine in adults.

摘要

目的

对慢性偏头痛（CM）或阵发性偏头痛（EM）患者使用依洛尤单抗的安全性数据进行汇总分析，该数据来自 4 项安慰剂对照的 2b 期和 3 期研究。

背景

目前需要一种有效的、安全的和耐受良好的预防性治疗方法，该方法特别针对偏头痛的病理生理学，以减少每月偏头痛发作 4 天或以上的 CM 或 EM 患者偏头痛发作的频率和严重程度。依洛尤单抗是一种完全人源化的单克隆抗体，靶向降钙素基因相关肽，这是一种参与偏头痛病理生理学的神经肽。

设计/方法：本分析纳入的 4 项安慰剂对照的 2b 期和 3 期研究为 16 周、多中心、随机、双盲、安慰剂对照、平行组研究，包括筛选访视、28 天预处理基线期和 12 周治疗期，最后一次研究药物给药后 4 周进行最终评估。安全性终点包括不良事件（AE）和免疫原性。

结果

共有 2566 名患者在所有研究中被随机分组（依洛尤单抗，n=1704；安慰剂，n=862），2563 名患者接受了治疗。研究中止的常见原因是患者退出（n=78）、患者失访（n=60）和 AE（n=50）。接受依洛尤单抗治疗的患者的平均（标准差）暴露时间为 83.8（13.6）天，总暴露量为 390.4 患者年，最大暴露量为 181 天。AE 多为轻至中度严重程度，在所有治疗组中，48%-69%的患者发生，大多数为注射部位反应（疼痛、硬结和红斑）。发生 2 例死亡（慢性阻塞性肺疾病和对苯海拉明的故意过量服用），均被研究者和申办方认为与研究药物无关。心血管不良事件、肝功能异常和过敏反应不常见，且在安慰剂和依洛尤单抗组中的发生率相似。