Analysis Supports Use of Erenumab Among Migraineurs With, Without History of Aura

Findings of a secondary analysis of randomized clinical trials revealed erenumab, a fully human monoclonal antibody, may be a safe and effective treatment option for migraineurs with and without history of aura. Results were published in JAMA Neurology.

Erenumab was approved in 2018 and is administered monthly via self-injection of a 70- or 140-mg dose. It works to block the calcitonin gene-related peptide (CGRP) receptor, which is believed to play a crucial role in the pathophysiology of migraine.

Although migraine with aura can occur in as many as one-third of migraineurs, currently, no well-established treatments are available to abort or prevent aura symptoms in these patients, researchers explained.

“Cortical spreading depression-like events are widely considered to be the underlying substrate of a migraine aura,” they said, adding, “it is unclear whether monoclonal antibodies, which are generally believed to be substantially restricted to the periphery, would be equally effective in migraine with aura vs without aura.”

In addition, previous research has shown migraineurs with aura have an elevated vascular risk, while the CGRP also functions to regulate vascular tone.

To better elucidate safety data on patients with migraine and aura, investigators carried out a post hoc subgroup analysis of clinical data from 4 randomized clinical trials of erenumab.

Studies included took place in treatment centers in North America, Europe, Russia, and Turkey between 2013 and 2019. All investigations included “a screening visit; a 4-week baseline phase; a 12- or 24-week placebo-controlled, double-blind treatment phase; an extension phase consisting of an open-label treatment phase or dose-blinded active treatment phase ranging from 28 weeks to 5 years; and safety follow-up visits 12 to 16 weeks after the last dose of erenumab,” authors wrote.

All participants were between the ages of 18 and 65 and had either episodic or chronic migraine. Efficacy analyses included pooled data from 3 trials on patients with episodic migraine while data from the trial of those with chronic migraine were assessed separately. Safety analyses used data from all 4 trials.

Of the 2682 patients randomized during the trials’ treatment phases, 52.2% received 1 or more dose of erenumab and 38.9% received a placebo. Among those who received erenumab, either 70 mg or 140 mg, or placebo, 1140 patients (46.7%) had a history of aura.

Mean (SD) patient age was 41.7 (11.2) years and the majority (84.1%) were female.

Analyses revealed:

• Reductions from baseline monthly migraine days (MMDs) and monthly acute migraine–specific medication (AMSM) days were greater in the erenumab than placebo groups in patients with and without a history of aura during the double-blind treatment phase; reductions were maintained throughout the extension phases
• In patients with episodic migraine and a history of aura, least-squares mean differences in change from baseline MMDs at week 12 were –1.1 (95% CI, –1.7 to –0.6) in those who received erenumab, 70 mg, and –0.9 (95% CI, –1.6 to –0.2) in those who received erenumab, 140 mg, compared with placebo
• In patients with chronic migraine with a history of aura, the least-squares mean differences from placebo treatment were –2.1 (95% CI, –3.8 to –0.5) in those who received erenumab, 70 mg, and –3.1 (95% CI, –4.8 to –1.4) in those who received erenumab, 140 mg

Researchers also found safety profiles were similar across treatment groups regardless of aura history and were “comparable to that of placebo over 12 weeks, with no increased emergence of adverse events over time.”

Similar to previous findings, higher rates of cardiovascular risk factors were seen among patients with a history of aura, including those of diabetes, and histories of hypertension and high blood pressure.

Discontinuations of erenumab due to adverse events were low in both subgroups but were slightly higher among those with a history of aura who took erenumab, authors noted.

Due to limited representations of patients from racial and ethnic minority groups and those older than 65, findings may not be generalizable, marking a limitation to the study.

Overall, “those who received erenumab in both subgroups attained greater reductions in MMDs from baseline than those who received placebo, with an increased proportion of patients achieving 50% or greater reductions in MMDs,” researchers concluded.

Reference

Ashina M, Goadsby PJ, Dodick DW, et al. Assessment of erenumab safety and efficacy in patients with migraine with and without aura: a secondary analysis of randomized clinical trials. JAMA Neurol. Published online December 20, 2021. doi:10.1001/jamaneurol.2021.4678