Efficacy and safety of gepants in migraine management: a narrative review focusing on atogepant and rimegepant.

Abstract

Gepants, oral antagonists of the calcitonin gene-related peptide (CGRP) receptor, represent a new therapeutic class in migraine management. This review aims to assess the efficacy and safety profile of the two gepants currently available in France: atogepant and rimegepant. A review of the literature was conducted in July 2024 using the PubMed, Cochrane Library, and Web of Science databases. Randomized controlled trials evaluating the efficacy and/or safety of atogepant and rimegepant in adult patients with migraine were included. Sixteen randomized controlled trials were selected (nine evaluating atogepant and seven evaluating rimegepant). In migraine prevention, atogepant significantly reduced the mean number of monthly migraine days (-0.7 to -2.4 days vs. placebo), with an improvement in quality-of-life scores (Migraine-Specific Quality of Life questionnaire-Role Function-Restrictive domain (MSQ-RFR): +9.9 to +10.8 points). Rimegepant, administered every other day, achieved a smaller reduction (-0.8 days/month) but was comparable to that observed with some anti-CGRP monoclonal antibodies. In acute treatment, a single dose of rimegepant 75 mg provided complete pain relief at 2 hours in 31-33% of patients versus 15% with placebo. Adverse events, mainly gastrointestinal (constipation and nausea), were generally mild to moderate, with no signal of hepatic or cardiovascular toxicity. Gepants represent a major therapeutic advance combining clinically meaningful efficacy with a favorable safety profile. Atogepant appears particularly promising for migraine prevention, whereas rimegepant offers an effective and well-tolerated option for acute treatment. Their use in clinical practice remains limited in France due to high cost and restricted reimbursement. Further real-world and long-term studies are needed to better define their place within current migraine management strategies.