Evaluation of vascular risk in patients with migraine with and without aura treated with erenumab: Post hoc analysis of pooled long-term clinical trial data

Headache. 2023 Mar;63(3):418-428. doi: 10.1111/head.14485.

Abstract

Objective: To assess cardiovascular (CV) safety of erenumab in clinical trial patients associated with degree of CV risk.

Background: Hypertension has been considered a theoretical risk associated with the inhibition of the calcitonin gene-related peptide pathway in migraine management, particularly in a patient population with pre-existing CV risk factors.

Methods: Data pooled from four double-blind, randomized trials were used to assess blood pressure (BP) changes and CV safety in patients grouped based on 10-year risk of cardiac, cerebrovascular, and peripheral artery disease as no-risk-factors, low-risk (>0% to ≤10%), moderate-risk (>10% to ≤20%), and high-risk (>20%) categories. CV safety was assessed as ischemic cardiovascular and cerebrovascular adverse events (ICCAE).

Results: There was no apparent difference between placebo- (N = 1032) and erenumab-treatment groups (70 mg, N = 885; 140 mg, N = 504) in clinical worsening of BP category from baseline to Months 1-3 (14% [143/1032] placebo vs. 13% [114/885] and 14% [71/504] for erenumab 70 and 140 mg, respectively) regardless of baseline BP category. The adverse event (AE) profile of erenumab was similar across CV risk categories throughout the long-term analysis. Erenumab-treated patients with high and moderate 10-year CV risk (N = 107) did not experience any ICCAEs during the double-blind treatment period; there was a single ICCAE (a cerebral dural venous sinus thrombosis) observed in the low-risk erenumab group (N = 273). There were no increases in AEs during the long-term extensions of up to 5 years (N = 2499; 3482 patient-years of exposure to erenumab) with exposure-adjusted incidence rates of cardio/cerebrovascular disorder AEs of 0.4, 0.5, 0.0, and 1.1 (per 100 patient-years) for no risk factor (N = 1805), low (N = 492), moderate (N = 121), and high (N = 81) 10-year CV risk groups, respectively.

Conclusions: Ischemic CV and cerebrovascular AEs were uncommon and the incidence rates were similar across the 10-year CV risk categories. This analysis helps provide more detail on the CV safety of erenumab.

Keywords: calcitonin gene-related peptide receptor; cardiovascular; erenumab; migraine; safety.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Antibodies, Monoclonal, Humanized / adverse effects
  • Calcitonin Gene-Related Peptide Receptor Antagonists / adverse effects
  • Double-Blind Method
  • Epilepsy* / drug therapy
  • Humans
  • Migraine Disorders* / chemically induced
  • Migraine Disorders* / drug therapy
  • Treatment Outcome

Substances

  • erenumab
  • Calcitonin Gene-Related Peptide Receptor Antagonists
  • Antibodies, Monoclonal, Humanized

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