美国Biohaven制药公司Robert Croop团队研究了口服瑞美吉泮预防偏头痛的疗效。2020年12月15日，该研究发表在《柳叶刀》杂志上。

瑞美吉泮是降钙素基因相关的肽受体拮抗剂，治疗急性偏头痛有一定的疗效和安全性。为了比较瑞美吉泮与安慰剂预防偏头痛的疗效，研究组在美国的92个地点进行了一项多中心、临床2/3期、随机、双盲、安慰剂对照试验，2018年11月14日至2019年8月30日，研究组共招募了747名至少有1年偏头痛病史的成人。

在4周的观察期后，将参与者随机分配，其中373名接受瑞美吉泮治疗，374名接受匹配的安慰剂治疗，隔日一次，持续12周。主要疗效终点为最后4周（9-12周）中每月偏头痛平均天数与4周观察期相比的变化。对接受至少一剂研究药物的患者的安全性进行分析。

共有695名参与者纳入疗效分析，其中瑞美吉泮组348名，安慰剂组347名。9-12周，瑞美吉泮组在每月平均偏头痛天数变化的主要终点上优于安慰剂组。与观察期相比，在9-12周内，瑞美吉泮组患者每月偏头痛平均天数减少4.3天，安慰剂组平均减少3.5天，差异显著。

741名参与者接受了研究药物并被纳入安全性分析。瑞美吉泮组370名患者中有133名（36％）报告了不良事件，安慰剂组371名患者中有133名（36％）。瑞美吉泮组中有7名（2％）参与者，安慰剂组中有4名（1％）参与者因不良事件而中止了研究；没有患者死亡。

研究结果表明，隔日服用瑞美吉泮可有效预防偏头痛，且安全耐受。

附：英文原文

Title: Oral rimegepant for preventive treatment of migraine: a phase 2/3, randomised, double-blind, placebo-controlled trial

Author: Robert Croop, Richard B Lipton, David Kudrow, David A Stock, Lisa Kamen, Charles M Conway, Elyse G Stock, Vladimir Coric, Peter J Goadsby

Issue&Volume: 2020-12-15

Abstract:

Background

Rimegepant is a calcitonin gene-related peptide receptor antagonist that has shown efficacy and safety in the acute treatment of migraine. We aimed to compare the efficacy of rimegepant with placebo for preventive treatment of migraine.

Methods

We did a multicentre, phase 2/3, randomised, double-blind, placebo-controlled trial at 92 sites in the USA. Adults with at least a 1-year history of migraine were recruited. After a 4-week observation period, eligible participants were randomised using an interactive web response system to oral rimegepant 75 mg or matching placebo every other day for 12 weeks (double-blind treatment phase). The primary efficacy endpoint was change from the 4-week observation period in the mean number of migraine days per month in the last 4 weeks of the double-blind treatment phase (weeks 9–12). Participants who received at least one dose of their assigned study medication and who had 14 days or more of data in the observation period and 14 days or more of data for at least one 4-week interval during the double-blind treatment phase were analysed for efficacy. Those who received at least one dose of study medication were analysed for safety. This study is registered with ClinicalTrials.gov, NCT03732638.

Findings

Between Nov 14, 2018, and Aug 30, 2019, 1591 participants were recruited and assessed for eligibility, of whom 747 were randomly allocated either rimegepant (n=373) or placebo (n=374). 695 participants were included in the analysis for efficacy, of whom 348 were assigned rimegepant and 347 were allocated placebo. Rimegepant was superior to placebo on the primary endpoint of change in the mean number of migraine days per month during weeks 9–12. The change from the observation period in mean number of migraine days per month during weeks 9–12 was 4·3 days (95% CI –4·8 to –3·9) with rimegepant and 3·5 days (–4·0 to –3·0) with placebo (least squares mean difference 0·8 days, 95% CI 1·46 to 0·20; p=0·0099). 741 participants received study medication and were included in the safety analysis. 133 (36%) of 370 patients who received rimegepant reported an adverse event, compared with 133 (36%) of 371 who received placebo. Seven (2%) participants who received rimegepant and four (1%) who received placebo discontinued the study due to an adverse event; no patients died.

Interpretation

Taken every other day, rimegepant was effective for preventive treatment of migraine. Tolerability was similar to that of placebo, and no unexpected or serious safety issues were noted.

DOI: 10.1016/S0140-6736(20)32544-7

Source: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)32544-7/fulltext