OBJECTIVES: In 2018, three medications that target the calcitonin gene-related peptide (CGRP) pathway received FDA approval for the preventive treatment of migraine: erenumab-aooe, fremanezumab-vfrm, and galcanezumab-gnlm. The real-world adverse event (AE) profile of CGRP pathway-targeted migraine preventive treatments was evaluated using post-marketing data.

METHODS: This retrospective analysis evaluated AEs spontaneously reported to the FDA for patients treated with erenumab, fremanezumab, and galcanezumab in the 6 months following their respective FDA approvals. Data were obtained from FAERS, the FDA’s database for safety surveillance. We evaluated cases in which the product was classified as the “primary suspect” associated with a reported AE. Reporting rates (RR) were calculated by dividing number of events in each AE category by estimated number of exposed subjects based on de-identified prescription data (IQVIA database) and multiplied by 1,000 to create a rate per 1,000 exposed. AEs were ranked based on frequency for each product.

RESULTS: The top ten RRs per 1,000 were as follows: erenumab: wrong technique (4.97), constipation (4.90), migraine (4.89), accidental product exposure (4.83), drug ineffective (3.68), headache (3.32), injection-site pain (2.94), nausea (2.94), under-dose (2.55), and fatigue (2.33); fremanezumab: headache (1.27), drug ineffective (1.14), migraine (1.01), nausea (0.91), injection-site pain (0.81), pruritus (0.73), injection-site erythema (0.71), injection-site pruritus (0.63), injection-site rash (0.63), injection-site swelling (0.58); and galcanezumab: injection-site pain (4.90), under-dose (3.86), headache (3.07), migraine (2.99), drug ineffective (1.69), injection-site erythema (1.58), injection-site swelling (1.25); injection-site pruritus (1.14), nausea (1.09), and product-dose omission (1.09).

CONCLUSIONS: Migraine, headache, or drug ineffective AEs were commonly reported for all three products, as were migraine-associated symptoms and injection-site reactions. Constipation ranked second for erenumab but did not make the top ten AEs for fremanezumab or galcanezumab. Cardiovascular events were not ranked in the top ten for any of the products.