Erenumab, a fully human monoclonal antibody that blocks calcitonin gene-related peptide (CGRP) approved for migraine prevention, does not increase the risk for cardiovascular, cerebrovascular, or peripheral vascular disease, according to study results published in Neurology.
As patients with migraine may have an increased risk for vascular events, and inhibition of CGRP may interfere with vasodilatory pathways during ischemia, the goal of this study was to assess the vascular safety of erenumab, including the risk for cardiovascular, cerebrovascular, and peripheral vascular disease.
The researchers used data from 4 double-blind, placebo-controlled migraine prevention studies of erenumab and their open-label extensions. Adverse events (AEs) that were new or worsened after the first dose of study treatment were recorded through 12 weeks after the last dose in studies with doses up to 70 mg, and through 16 weeks after the last dose in studies with doses up to 140 mg.
In total, during 12 weeks of double-blind treatment across the 4 studies, 2443 subjects received placebo (1043 subjects), erenumab 70 mg (893 subjects), or erenumab 140 mg (507 subjects). The safety analysis of AE included 2499 patients that received ≥1 dose of erenumab.
The incidence of AEs was similar across the placebo, erenumab 70 mg, and erenumab 140 mg groups, with no evidence of dose dependency for safety. The incidence of AEs and serious AEs across the placebo and erenumab treatment groups was similar, regardless of the number of vascular risk factors at baseline.
Erenumab treatment had no relevant effect on blood pressure compared with placebo. Hypertension was documented in 9 patients (0.9%) receiving placebo, 7 patients (0.8%) receiving erenumab 70 mg, and 1 patient (0.2%) receiving erenumab 140 mg.
In the 24-hour continuous blood pressure monitoring study, systolic and diastolic blood pressure in healthy control individuals were similar in the erenumab 70 mg group and the erenumab 140 mg group compared with the placebo group, and erenumab had no effect on the diurnal pattern of blood pressure.
Vascular ischemic events occurred during open-label erenumab treatment and were confounded with plausible alternative etiologies.
The researchers identified 18 patients with AEs that fulfilled criteria for adjudication, of which 4 were positively adjudicated as cardiovascular in origin. These AEs all occurred during open-label erenumab treatment, and the investigators concluded that they were not related to erenumab treatment.
Patients who used acute migraine-specific medications at baseline had similar incidences of AEs and serious AEs across the placebo and erenumab treatment groups. Furthermore, the incidence of AEs across the placebo and erenumab groups was similar, regardless of the number of vascular risk factors at baseline.
The study had several limitations, according to the researchers, including the exclusion of patients with major vascular events within 12 months before each study, no placebo comparator group available for the longer-term safety data, and inclusion of only 4 vascular events.
“In this integrated analysis, erenumab had a vascular safety profile comparable to that of placebo over 12 weeks, and the overall safety profiles for erenumab and placebo were similar regardless of whether patients also used an acute migraine-specific medication or had risk factors for vascular events,” concluded the researchers.
Disclosure: This clinical trial was supported by Amgen Inc. and Novartis. Please see the original reference for a full list of authors’ disclosures.
Kudrow D, Pascual J, Winner PK, et al. Vascular safety of erenumab for migraine prevention [published online December 18, 2019]. Neurology. doi:10.1212/WNL.0000000000008743