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

• Published in: European journal of clinical pharmacology 2022-09, Vol.78 (9), p.1365-1376
• Main Authors: Lee, Seoyeon, Staatz, Christine E., Han, Nayoung, Baek, In-hwan
• Format: Article
• Language: English
• Subjects: Adverse events; Biomedical and Life Sciences; Biomedicine; Calcitonin; Calcitonin gene-related peptide; Clinical trials; Diarrhea; Headache; Meta-analysis; Migraine; Nausea; Paresthesia; Peptides; Pharmacology/Toxicology; Placebos; Review; Safety; Vomiting
• ISSN: 0031-6970; 1432-1041
• DOI: 10.1007/s00228-022-03347-6

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.