The Efficacy and Safety of Rimegepant Every Other Day as Preventive Treatment for Migraine: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

BACKGROUND

Rimegepant is an oral CGRP receptor antagonist initially approved for the acute treatment of migraine, demonstrating rapid onset of action and a favorable tolerability profile. Recently, a limited number of randomized controlled trials have evaluated its prophylactic use. The aim of this systematic review and meta-analysis is to assess the effectiveness and safety of rimegepant as a preventive therapy for migraine. METHODOLOGY: This systematic review and meta-analysis followed PRISMA guidelines and was registered in PROSPERO (ID: CRD420251142208). We systematically searched Embase, PubMed, Scopus, Cochrane Central Register of Controlled Trials, Science Direct, and Clinical trials.gov from inception to March 2026. Keywords and MeSH terms were applied to identify randomized controlled trials assessing rimegepant for migraine prevention compared with placebo. Primary efficacy endpoints were the change from the observation period in the mean number of monthly migraine days over the entire study period ( Weeks 1–12 ), in the last month (Weeks 9–12 ), and in the first month (Weeks 1–4 ) Additional primary outcomes include the change from baseline in MSQ scores, the proportion of participants achieving ≥ 50% reduction in moderate to severe migraine attacks from the observation phase, and the reported safety outcomes.

RESULTS

Screening of 792 articles yielded four randomized controlled trials comprising 2,365 participants. Rimegepant significantly reduced monthly migraine days compared with placebo : in the first four weeks (MD − 1.49; 95% CI: −1.84 to − 1.15, p < 0.00001; I²=31%), over the entire study period (MD − 0.98; 95% CI: − 1.33 to − 0.64, p < 0.00001; I²=43%), and in the last four weeks (MD − 0.91; 95% CI: −1.39 to − 0.44, p < 0.00001; I²=47%). Migraine Specific Quality-of-life score was improved (MD 4.36; 95% CI: 2.80 to 5.92, p < 0.00001; I²=9%). Responders rate of ≥ 50% reduction in the number of moderate-to-severe migraine attacks : in the last four weeks was higher in rimegepant group (RR 1.19; 95% CI: 1.04 to 1.36, p = 0.010;I²=0) and over the entire study period (RR 1.72; 95% CI: 0.86 to 3.34, p = 0.12;I²=92). Adverse events leading to discontinuation were higher in rimegepant (RR 1.76; 95% CI: 0.90 to 3.46, p = 0.10; I²=0). Rimegepant was associated with higher rates of nausea (RR 2.02; 95% CI: 1.02 to 4.00, p = 0.05; I²=0).

CONCLUSION

To our knowledge, this is the first systematic review and meta-analysis evaluating rimegepant for migraine prophylaxis. Rimegepant showed statistically significant pooled effect in reducing monthly migraine days and was associated with improved quality of life. However, further studies are warranted to prove the clinical effectiveness of rimegepant as preventive treatment for migraine.