Disproportionality analysis of Raynaud’s phenomenon associated with calcitonin gene-related peptide inhibitors using the Food and Drug Administration adverse event reporting system

Abstract

Abstract Raynaud’s phenomenon is a vascular condition characterized by episodic vasoconstriction, and recent reports suggest a potential link between calcitonin gene-related peptide (CGRP) inhibitors, used for migraine treatment, and the onset of this condition. This study evaluated the association between CGRP inhibitors and Raynaud’s phenomenon using data from the FDA Adverse Event Reporting System (FAERS). A retrospective analysis of adverse events from the approval year of each drug through August 2023 was conducted. Disproportionality was assessed using Reporting Odds Ratios (ROR) and Information Components (IC), with significant signals of disproportionate reporting (SDR) identified by a lower 95% confidence interval (CI) for ROR > 1.0 and IC > 0. Intra-class and inter-class analyses were conducted to compare SDRs among CGRP inhibitors and other migraine therapies, including triptans, beta-blockers, and anticonvulsants. CGRP inhibitors demonstrated significant SDRs for Raynaud’s phenomenon (ROR 19.12; 95% CI 15.44–23.69), with rimegepant, ubrogepant, and atogepant showing particularly strong signals. Intra-class analysis revealed a significant SDR only for galcanezumab (ROR 2.01; 95% CI 1.28–3.17). Inter-class analysis indicated significant SDRs for CGRP inhibitors compared to beta-blockers, anticonvulsants, and celecoxib, but not triptans. These findings underscore the importance of ongoing pharmacovigilance and further research to validate these associations and ensure patient safety.

Keywords

• Calcitonin gene-related peptide inhibitors
• Raynaud’s phenomenon
• Disproportionality analysis
• Migraine
• Pharmacovigilance
• Drug safety