Comparative Efficacy and Safety of Five Anti-calcitonin Gene-related Peptide Agents for Migraine Prevention

Objectives:Anti-calcitonin gene-related peptide (CGRP) agents are some of the newest preventive medications for migraine. There is limited literature comparing the efficacy of the most recent CGRP antagonist, atogepant, to CGRP monoclonal antibodies for migraine prevention. In this network meta-analysis, the efficacy and safety of migraine treatments including different doses of atogepant and CGRP monoclonal antibodies were evaluated to provide a reference for future clinical trials.Materials and Methods:A search using PubMed, Embase, and Cochrane Library identified all randomized controlled trials published through May 2022 and including patients diagnosed with episodic or chronic migraine and treated with erenumab, fremanezumab, eptinezumab, galcanezumab, atogepant, or placebo. The primary outcomes were the reduction of monthly migraine days, 50% response rate, and the number of adverse events (AEs). The Cochrane Collaboration tool was used to assess the risk of bias.Results:In this study, 24 articles were considered for analysis. Regarding efficacy, all interventions were superior to placebo with a statistically significant difference. The most effective intervention was monthly fremanezumab 225 mg in change from baseline of migraine days (standard mean difference = -0.49, 95% CI: -0.62, -0.37) and 50% response rate (risk ratio = 2.98, 95% CI: 2.16,4.10), while the optimal choice for reducing acute medication days was monthly erenumab 140 mg (standard mean difference = -0.68, 95% CI: -0.79, -0.58). In terms of AEs, all therapies and placebo did not achieve statistical significance except for monthly galcanezumab 240 mg and quarterly fremanezumab 675 mg. There was no significant difference in discontinuation due to AEs between interventions and placebo.Discussion:All anti-CGRP agents were more effective than placebo in migraine prevention. Overall, monthly fremanezumab 225 mg, monthly erenumab 140 mg, and daily atogepant 60 mg were effective interventions with fewer side effects.