Abstract
BackgroundPatients with migraine have an increased relative risk of cardio- and cerebrovascular events, and some migraine treatments may exacerbate this risk. The primary objective of this analysis was to determine whether the rate of cardiovascular adverse events was higher for patients with migraine treated with the migraine-preventive eptinezumab, compared with patients receiving placebo.MethodsCardiovascular outcomes in patients with migraine were pooled across four clinical trials (phase 1b, phase 2, and two phase 3 trials) for use of eptinezumab as a preventive migraine treatment for up to 1 year. In all studies, treatment-emergent adverse events (TEAEs) that occurred after the first dose of study treatment (eptinezumab 100 mg, 300 mg, 1000 mg, or placebo) and vital signs were recorded through study completion.ResultsCardiovascular TEAEs were rare across all four clinical trials, and rates were similar between patients receiving eptinezumab and those receiving placebo. Cardiovascular TEAEs that did occur were mild or moderate in severity; there were no serious adverse events as per FDA definition. Vital signs (systolic blood pressure, diastolic blood pressure, and heart rate) were not meaningfully different across treatment groups over the course of 56 weeks, compared to placebo. Treatment with eptinezumab did not result in significant new or changed cardiovascular medications used concomitantly compared to placebo.ConclusionsIn this post hoc analysis of four clinical trials for eptinezumab, doses of 100 mg, 300 mg, and 1000 mg (more than 3 times the highest approved dose) were not associated with clinically relevant changes in vital signs or significant changes in concomitant cardiovascular medication usage, and had low incidences of cardiovascular TEAEs, comparable to placebo.Trial registrationNCT01772524 (Study 2), 01/21/2013; NCT02275117 (Study 5), 10/27/2014; NCT02559895 (PROMISE-1), 09/25/2017; NCT02974153 (PROMISE-2), 11/28/2016
Highlights
Patients with migraine have an increased relative risk of cardio- and cerebrovascular events, and some migraine treatments may exacerbate this risk
Patients suffering from migraine, especially those experiencing migraine with aura, have an increased relative risk for vascular comorbidities and events, such as stroke and myocardial ischemia, as compared to patients without migraine [3,4,5,6,7]
There are currently four monoclonal antibodies approved by the U.S Food and Drug Administration (FDA) for the prevention of migraine that either bind to the Calcitonin gene-related peptide (CGRP) ligand or to the canonical CGRP receptor
Summary
Patients with migraine have an increased relative risk of cardio- and cerebrovascular events, and some migraine treatments may exacerbate this risk. Patients suffering from migraine, especially those experiencing migraine with aura, have an increased relative risk for vascular comorbidities and events, such as stroke and myocardial ischemia, as compared to patients without migraine (or migraine without aura) [3,4,5,6,7]. There are currently four monoclonal antibodies approved by the U.S Food and Drug Administration (FDA) for the prevention of migraine that either bind to the CGRP ligand (fremanezumab-vfrm; galcanezumabglnm; and eptinezumab-jjmr) or to the canonical CGRP receptor (erenumab-aooe [11]). A study in mice found that gepants (olcegepant and rimegepant), which are CGRP-receptor antagonists, worsened ischemic stroke [16], raising concerns that CGRP antagonism may increase the potential risk in patients at-risk for stroke or myocardial infarction. The overall importance of the CGRP pathway, when compared with other vasodilatory pathways, during ischemia (e.g., myocardial ischemia) is yet to be established [6, 10]
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