Safety evaluation of oral calcitonin-gene-related peptide receptor antagonists in patients with acute migraine: a systematic review and meta-analysis

Eur J Clin Pharmacol. 2022 Sep;78(9):1365-1376. doi: 10.1007/s00228-022-03347-6. Epub 2022 Jun 22.

Abstract

Objective: Calcitonin gene-related peptide (CGRP) receptor antagonists have been suggested as novel treatments for acute migraine. This study aimed to use meta-analysis to compare the safety and tolerability of five existing oral CGRP receptor antagonists (BI44370TA, MK-3207, rimegepant, telcagepant, and ubrogepant) with that of a placebo or triptans against acute migraine.

Methods: Five prominent databases were searched to identify randomized controlled trials on this topic. The primary safety outcomes of interest were any adverse events (AEs) and treatment-related adverse events (TRAEs), and secondary outcomes were individual events, namely diarrhea, dizziness, dry mouth, fatigue, nausea, paresthesia, somnolence, upper abdominal pain, and vomiting.

Results: Fifteen studies met the eligibility criteria and were examined in detail. Although, compared to placebo, oral CGRP receptor antagonists significantly increased the incidence of any AEs (risk ratio [RR] = 1.15; 95% confidence interval [CI] = 1.07-1.23), there was no difference in the incidence of TRAEs (RR = 1.18; 95% CI = 1.00-1.38). Moreover, CGRP receptor antagonists were safer than triptans with respect to primary safety outcomes, such as any AEs (RR = 0.78; 95% CI = 0.63-0.98) and TRAEs (RR = 0.68; 95% CI = 0.58-0.79).

Conclusion: Despite oral CGRP receptor antagonists posing a significantly higher risk of AEs when compared to placebo, CGRP receptor antagonists have a favorable safety profile compared to triptans. Our findings inform strategies to enhance safety and tolerability in the treatment of acute migraine.

Keywords: Calcitonin gene-related peptide receptor antagonists; Meta-analysis; Migraine; Safety; Triptan.

Publication types

  • Meta-Analysis
  • Systematic Review

MeSH terms

  • Calcitonin / therapeutic use
  • Calcitonin Gene-Related Peptide Receptor Antagonists* / adverse effects
  • Humans
  • Migraine Disorders* / drug therapy
  • Receptors, Peptide / therapeutic use
  • Tryptamines / adverse effects

Substances

  • Calcitonin Gene-Related Peptide Receptor Antagonists
  • Receptors, Peptide
  • Tryptamines
  • Calcitonin