Identifying signals of disproportionate reporting for calcitonin gene-related peptide inhibitors: real-world evidence from the FDA adverse event reporting system.

BACKGROUND

Calcitonin gene-related peptide (CGRP) inhibitors have been FDA-approved for migraine prophylaxis and relief. However, their safety profile remains uncertain. This study analyzes adverse events (AEs) and signals of disproportionate reporting (SDRs) using the FDA Adverse Event Reporting System (FAERS).

RESEARCH DESIGN AND

METHODS

We analyzed FAERS reports from approval through Q2 2023, standardizing terms using preferred terminology and system organ class (SOCs) classifications. Disproportionality analyses (ROR, PRR, IC) identified SDRs and inclusion in FDA prescribing information was reviewed. Additional analyses included comparisons with other migraine drugs, indication-based sensitivity analyses and causality assessment using the Bradford Hill framework.

RESULTS

Galcanezumab showed strong signals for underdose (ROR 47.4; 95% CI 43.79-51.3), alopecia (5.72; 5.09-6.43), and constipation (6.01; 5.35-6.75), while fremanezumab exhibited notable associations with alopecia (6.9; 5.72-8.33) and weight increased (6.34; 5.18-7.76). Among gepants, rimegepant was linked to somnolence (4.52; 3.57-5.73) and dizziness (3.73; 3.15-4.42) and atogepant showed a strong signal for therapy interruption (16.58; 12.86-21.38).

CONCLUSIONS

This study highlights CGRP inhibitor-associated AEs, underscoring the need for clinical monitoring and risk identification. Early detection of AEs and SDRs can inform protective measures to enhance patient safety.