The efficacy and safety of zavegepant nasal inhalation versus oral calcitonin-gene related peptide receptor antagonists in the acute treatment of migraine: a systematic review and network meta-analysis of the literature

Background The latest randomized controlled trial (RCT) revealed that zavegepant, a new nasal inhalation calcitonin gene-related peptide (CGRP) receptor antagonist, has a clear efficacy in the acute treatment of migraine. However, whether the efficacy of this new nasal inhalation drug is better than other oral CGRP receptor antagonists remained to be confirmed. Therefore, we designed this network meta-analysis (NMA) to provide a reference for the clinical application of zavegepant. Methods We systematically searched PubMed, EMBASE, The Cochrane Register of Controlled Trials, Scopus, and Web of Science up to December 1, 2024. RCTs using CGRP receptor antagonists (excluding non-randomized, non-English or no extractable data trials) to treat adult patients suffering from acute migraine were included. STATA 18.0 and R STUDIO were used for the statistical analysis. Results A total of 15 randomized clinical trials with 11,179 patients were included. Compared with the placebo, zavegepant 10 mg demonstrated a significantly higher efficiency for pain freedom at 2 h (relative risk (RR) = 1.54, 95% CI: 1.28-1.82, I2 = 0.0%, P < 0.001) and most bothersome symptom (MBS) freedom at 2 h (RR = 1.26, 95% CI: 1.13-1.42, I2 = 0.0%, P < 0.001), but did not show significant superiority over oral CGRP receptor antagonists. In terms of safety, zavegepant 10 mg was significantly inferior to placebo but not inferior to oral CGRP receptor antagonists. Conclusion Zavegepant 10 mg can quickly relieve symptoms and has no significant difference in safety compared with oral drugs, which can provide rapid and safe efficacy in the acute treatment of migraine. However, compared with other oral CGRP receptor antagonists, zavegepant 10 mg by nasal inhalation has no obvious advantage in long-term symptom relief rate.