Adverse event analysis and signal detection of calcitonin gene-related peptide inhibitors using the FDA Adverse Event Reporting System database

Abstract

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). Methods We examined AEs reported to FAERS from the approval date to August 2023, standardizing data using preferred terms and system organ classes (SOCs). Disproportionality analyses, including reporting odds ratio (ROR), proportional reporting ratio (PRR) and information component (IC), were used to quantify SDRs. Inclusion in FDA prescribing information was also checked. Results Potential safety signals for monoclonal antibodies, not listed in FDA prescribing information, included psychiatric disorders (e.g., depression - erenumab: ROR 1.97; 95% CI 1.78–2.17) and vascular disorders (e.g., hypertension - erenumab: ROR 1.44; 1.29–1.62). Epitinezumab was associated with throat irritation (ROR 36.94; 30.66–44.52). Commonly reported SOCs included general disorders and administration site conditions (27,578 events; 43.68%), injury, poisoning and procedural complications (26,201 events; 41.5%), and nervous system disorders (15,788 events; 25.01%). Conclusion 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.