Abstract
BACKGROUND: Gepants, selective antagonists of the calcitonin gene-related peptide (CGRP) receptor, and monoclonal antibodies targeting CGRP or its receptor (anti-CGRP mAbs) are promising migraine treatments, demonstrating superior tolerability than traditional preventives. While their efficacy over placebo is established, their comparative benefit-risk profiles remain to be fully elucidated. OBJECTIVE: To indirectly compare the benefit-risk ratios of gepants with anti-CGRP mAbs and repurposed preventives. METHODS: A comprehensive search of PubMed/MEDLINE and ClinicalTrials.gov was conducted to identify phase-3, placebo-controlled trials of gepants (atogepant, rimegepant), anti-CGRP mAbs (eptinezumab, erenumab, fremanezumab, galcanezumab), and traditional treatments (propranolol, topiramate, onabotulinumtoxinA). The number needed to treat (NNT) for achieving ≥50% reduction in migraine days and the number needed to harm (NNH) for adverse effects were calculated to determine the likelihood to help versus harm (LHH) values. RESULTS: Twenty-seven studies were included: 15 of mAbs, 4 of gepants, 2 of onabotulinumtoxin A, and 6 of standard treatments. Atogepant and fremanezumab exhibited the highest LHH in episodic migraine, and galcanezumab and eptinezumab performed favorably in chronic migraine concerning treatment discontinuation and treatment-related adverse effects. CONCLUSIONS: Anti-CGRP/R medications present a more favorable benefit/risk ratio than traditional treatments. These findings, combined with individual patient histories and preferences, can inform clinical decision-making.