Rimegepant for the acute treatment of migraine: a systematic review and meta-analysis.

OBJECTIVE

To determine the efficacy and tolerability of a single 75 mg oral dose of rimegepant compared with placebo for the acute treatment of migraine attacks in adults.

METHODS

A systematic review and meta-analysis were conducted in accordance with PRISMA guidelines, with the protocol prospectively registered in PROSPERO (Identifier: CRD420251042015). Comprehensive searches of CENTRAL, ClinicalTrials.gov, EMBASE, EUCTR, PubMed, and WHO ICTRP were performed from database inception to December 2025, without language restrictions. Supplementary sources were also reviewed, including regulatory and sponsor materials such as FDA and EMA submissions and entries in the Pfizer and Biohaven clinical trial registries. Eligible studies were double-blind randomized controlled trials enrolling adults (≥ 18 years) with migraine (with or without aura) who received a single 75 mg oral dose of rimegepant compared with placebo for the acute treatment of migraine attacks. The co-primary outcomes were pain freedom at 2 h post-dose and sustained pain freedom from 2 to 24 h post-dose. Tolerability outcomes included all non-serious adverse events (AEs) following dosing, whereas safety outcomes comprised serious adverse events. Risk of bias was evaluated using the Cochrane RoB 2 tool, and certainty of evidence was assessed using the GRADE framework. Pooled risk ratios (RRs) with 95% confidence intervals (CIs) were calculated using a random-effects model, and heterogeneity was quantified using the I² and τ² statistics.

RESULTS

Seven double-blind RCTs (one phase II, five phase III, one phase IV) comprising 6,734 participants met the inclusion criteria. Two hours post-dose, 19.8% of participants receiving rimegepant and 10.7% receiving placebo achieved pain freedom (RR, 1.93; 95% CI, 1.51-2.47; P < 0.001; NNT = 10). Sustained pain freedom from 2 to 24 h was achieved by 14.2% of those receiving rimegepant, compared with 6.3% receiving placebo (RR, 2.39; 95% CI, 1.75-3.27; P < 0.001; NNT = 11). AEs occurred in 14.3% of rimegepant-treated and 12.7% of placebo-treated participants (RR, 1.14; 95% CI, 1.00-1.30; P = 0.056; NNH = 55). Risk of bias was judged as low across the included trials.

CONCLUSIONS

Rimegepant 75 mg provides modest yet clinically meaningful efficacy with favorable short-term tolerability for the acute treatment of migraine attacks. These findings support its use as an effective treatment option for adults with inadequate response, contraindications, or intolerance to first- or second-line therapies.

CLINICAL TRIALS NUMBER: Not applicable.