Erenumab Appears Safe, Effective in Migraine With Aura

Migraine prevention drug erenumab (Aimovig) appeared safe and effective in patients both with and without aura, pooled trial data showed.

In a post hoc secondary analysis of four randomized clinical trials, erenumab was associated with reduced migraine frequency and fewer days of using acute migraine-specific medication in both people with and those without aura, reported Messoud Ashina, MD, PhD, DMSc, of the University of Copenhagen in Denmark, and co-authors.

No differences were observed in safety profiles of patients with and without history of aura, the researchers wrote in JAMA Neurology.

Migraine with aura occurs in about a third of patients with migraine. "Most patients with migraine with aura also report migraine attacks without aura," Ashina told MedPage Today. "The impact of co-existing aura subtype of migraine on the efficacy of preventive treatments for migraine is debatable."

A number of studies have, indeed, suggested different response to acute and preventive therapies for migraine with aura versus without it.

Erenumab, approved in 2018 for migraine prevention, is designed to block the calcitonin gene-related peptide (CGRP) receptor. CGRP is a potent vasodilator, and vascular dysfunction is believed to play a significant role in migraine.

A recent FDA analysis of postmarketing case reports suggested erenumab was linked to elevated blood pressure that required treatment and, in some cases, hospitalization. In 2021, a warning about new-onset or worsening of pre-existing hypertension was added to the erenumab drug label.

In the pooled trial analysis, safety profiles were similar across treatment groups regardless of aura history over 12 weeks. Adverse events did not increase over time. Cardiovascular, cerebrovascular, and hypertension adverse event rates were low and similar among subgroups. In the open-label treatment phase, hypertension-related adverse events occurred in 2.2% of migraine patients with aura and 2.3% of patients without aura.

Ashina and colleagues assessed data from four double-blind, placebo-controlled randomized clinical trials in North America, Europe, Russia, and Turkey that were conducted between August 2013 and November 2019 with patients who had episodic or chronic migraine.

Patients were excluded from the trials if they had a myocardial infarction, stroke, transient ischemic attack, unstable angina, or coronary artery bypass surgery or another revascularization procedure within 12 months before study screening. Two clinical trials excluded patients if they had poorly-controlled hypertension.

Of 2,682 patients randomized in the four trials (mean age about 42, 84% women), 1,400 people received one or more dose of erenumab and 1,043 people received placebo. A total of 429 patients with aura received erenumab 70 mg, and 231 patients with aura received erenumab 140 mg once a month in the trial. The recommended erenumab dosage is now 70 mg once a month, though some patients benefit from 140 mg once monthly.

Cardiovascular risk factors -- diabetes, history of hypertension, high blood pressure, high lipids, and BMI of 30 or higher -- were more prominent among participants with a history of aura.

Primary endpoints were reductions in mean monthly migraine days and acute migraine-specific medication days from baseline. Reductions in both endpoints were greater in erenumab than placebo groups, both with and without a history of aura, during the double-blind treatment phase. These reductions were maintained throughout the extension phases.

Episodic migraine patients with a history of aura who received erenumab 70 mg had least-squares mean differences in change of mean monthly migraine days from baseline at week 12 of –1.1 (95% CI –1.7 to –0.6) compared with placebo. Those who received erenumab 140 mg had mean differences of –0.9 (95% CI –1.6 to –0.2) from placebo.

Chronic migraine patients with a history of aura showed least-squares mean differences in mean monthly migraine days versus placebo treatment of –2.1 (95% CI –3.8 to –0.5) on erenumab 70 mg and –3.1 (95% CI –4.8 to –1.4) on erenumab 140 mg.

Changes in acute migraine-specific medication days followed similar patterns for both episodic and chronic migraine patients.

The study has several limitations, researchers acknowledged. Most participants where white, and findings might not apply to other populations. Patients without aura had higher exposure to preventive and acute treatments, and time of exposure to erenumab varied.

The analysis also looked only at people who qualified for clinical trials, not real-world migraine patients.

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