Adverse Event Profiles of Therapies that Target the Calcitonin Gene-Related Peptide (CGRP) Pathway, During the First Six Months After Launch: A Real-world Data Analysis Using the FDA Adverse Events Reporting System (FAERS)
Stephen D. Silberstein1, Shoshana Reshef2, Joshua M. Cohen2, Sanjay Gandhi2, Michael Seminerio2, Verena Ramirez Campos2, Yoel Kessler2, Stephen Thompson2, Andrew Blumenfeld3
1Jefferson Headache Center, 2Teva Pharmaceuticals Industries, 3The Neurology Center
To gain insight into the real-world adverse event (AE) profile of CGRP pathway-targeted migraine preventive treatments.
Since May 2018, three medications that target the CGRP pathway have received FDA approval for the preventive treatment of migraine: erenumab-aooe, fremanezumab-vfrm, and galcanezumab-gnlm. Post-marketing data are valuable for understanding medication safety in a real-world setting.

This retrospective analysis evaluated AEs spontaneously reported to the FDA during the first 6 months post-approval for patients treated with erenumab, fremanezumab, and galcanezumab. 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.

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); 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).

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.