From the Departments of Neurology and Epidemiology and Population Health, Albert Einstein College of Medicine, and Montefiore Medical Center - both in Bronx, NY (R.B.L.); Biohaven Pharmaceuticals, New Haven, CT (R.C., E.G.S., D.A.S., B.A.M., M.F., G.M.D., C.M.C., V.C.); NIHR-Wellcome Trust King's Clinical Research Facility, King's College Hospital-South London and Maudsley Biomedical Research Centre, King's College London, London (P.J.G.); and the University of California, San Francisco, San Francisco (P.J.G.).
N Engl J Med. 2019 Jul 11;381(2):142-149. doi: 10.1056/NEJMoa1811090.
Calcitonin gene-related peptide receptor has been implicated in the pathogenesis of migraine. Rimegepant is an orally administered, small-molecule, calcitonin gene-related peptide receptor antagonist that may be effective in acute migraine treatment.
In a multicenter, double-blind, phase 3 trial, we randomly assigned adults with at least a 1-year history of migraine and two to eight migraine attacks of moderate or severe intensity per month to receive rimegepant orally at a dose of 75 mg or matching placebo for the treatment of a single migraine attack. The primary end points were freedom from pain and freedom from the most bothersome symptom (other than pain) identified by the patient, both of which were assessed 2 hours after the dose of rimegepant or placebo was administered.
A total of 1186 patients were randomly assigned to receive rimegepant (594 patients) or placebo (592 patients); of these, 537 patients in the rimegepant group and 535 patients in the placebo group could be evaluated for efficacy. The overall mean age of the patients evaluated for efficacy was 40.6 years, and 88.7% were women. In a modified intention-to-treat analysis, the percentage of patients who were pain-free 2 hours after receiving the dose was 19.6% in the rimegepant group and 12.0% in the placebo group (absolute difference, 7.6 percentage points; 95% confidence interval [CI], 3.3 to 11.9; P<0.001). The percentage of patients who were free from their most bothersome symptom 2 hours after the dose was 37.6% in the rimegepant group and 25.2% in the placebo group (absolute difference, 12.4 percentage points; 95% CI, 6.9 to 17.9; P<0.001). The most common adverse events were nausea and urinary tract infection.
Treatment of a migraine attack with the oral calcitonin gene-related peptide receptor antagonist rimegepant resulted in a higher percentage of patients who were free of pain and free from their most bothersome symptom than placebo. (Funded by Biohaven Pharmaceuticals; ClinicalTrials.gov number, NCT03237845.).
降钙素基因相关肽受体与偏头痛的发病机制有关。利马曲班是一种口服的、小分子的降钙素基因相关肽受体拮抗剂，可能对急性偏头痛的治疗有效。
在一项多中心、双盲、3 期临床试验中，我们将至少有 1 年偏头痛病史且每月有 2 至 8 次中度或重度偏头痛发作的成年人随机分为两组，分别接受利马曲班口服 75mg 或匹配安慰剂治疗单次偏头痛发作。主要终点是治疗后 2 小时患者无疼痛和无最困扰症状（除疼痛外）的比例，其中最困扰症状由患者确定。
共有 1186 名患者被随机分为利马曲班组（594 名患者）或安慰剂组（592 名患者）；其中，利马曲班组有 537 名患者和安慰剂组有 535 名患者可进行疗效评估。疗效评估患者的平均年龄为 40.6 岁，88.7%为女性。在改良意向治疗分析中，治疗后 2 小时无疼痛的患者比例在利马曲班组为 19.6%，安慰剂组为 12.0%（绝对差值，7.6 个百分点；95%置信区间[CI]，3.3 至 11.9；P<0.001）。治疗后 2 小时无最困扰症状的患者比例在利马曲班组为 37.6%，安慰剂组为 25.2%（绝对差值，12.4 个百分点；95%CI，6.9 至 17.9；P<0.001）。最常见的不良反应是恶心和尿路感染。
用口服降钙素基因相关肽受体拮抗剂利马曲班治疗偏头痛发作，与安慰剂相比，有更高比例的患者无疼痛和无最困扰症状。（由佰奥本辰制药公司资助；ClinicalTrials.gov 注册号：NCT03237845）。
