Safety and tolerability of fremanezumab in patients with episodic and chronic migraine: a pooled analysis of phase 3 studies. (July 2022)

• Record Type: Journal Article
• Authors: Diener, Hans Christoph; McAllister, Peter; Jürgens, Tim P; Kessler, Yoel; Ning, Xiaoping; Cohen, Joshua M; Campos, Verena Ramirez; Barash, Steve; Silberstein, Stephen D
• Is Part Of: Cephalalgia. Volume 42:Number 8(2022)
• Page Start: 769
• Page End: 780
• Publication Date: 2022-07
• Subjects: fremanezumab -- calcitonin gene-related peptide -- safety -- cardiovascular; Headache -- Periodicals; 616.8491
• DOI: 10.1177/03331024221076485
• Languages: English
• ISSNs: 0333-1024

Abstract

Background: Fremanezumab, a fully humanized monoclonal antibody that selectively targets calcitonin gene-related peptide, has demonstrated efficacy for preventive treatment of episodic and chronic migraine. Since calcitonin gene-related peptide is expressed within the cardio- and cerebrovascular system and may have cardioprotective effects, it is critical to understand the cardio- and cerebrovascular safety of fremanezumab. Methods: This was a pooled analysis of three randomized, double-blind, placebo-controlled, phase 3, 12-week trials in which patients with episodic migraine or chronic migraine received quarterly fremanezumab, monthly fremanezumab, or placebo. Incidences of overall and serious adverse events were analyzed. Cardio- and cerebrovascular adverse events (CVAEs) were analyzed in subgroups stratified by cardio- and cerebrovascular medical history, cardiovascular risk factors (CVRFs), and use of cardio- and cerebrovascular medications or triptans. Results: Two thousand, eight hundred and forty-two patients were included in the study. Overall (58–65%) and serious adverse events (<1–2%) occurred in similar proportions across fremanezumab and placebo groups. CVAEs were infrequent, regardless of cardio- and cerebrovascular medical history (2–6%). CVAEs occurred in low, similar proportions of patients with CVRFs and those using cardio- and cerebrovascular medications or triptans. No cardio- and cerebrovascular signals were identified. Conclusion: Fremanezumab demonstrated a favorable overall and cardio- and cerebrovascular safety profile in more than 2800 patients with episodic migraine or chronic migraine, regardless of cardio- and cerebrovascular medical history, CVRFs, or medication use. Trial Registrations: NCT02629861 (HALO EM, https://clinicaltrials.gov/ct2/show/NCT02629861 ), NCT02621931 (HALO CM, https://clinicaltrials.gov/ct2/show/NCT02621931 ), NCT03308968 (FOCUS, https://clinicaltrials.gov/ct2/ show/NCT03308968 )