Erenumab reduced monthly migraine days (MMDs) and acute migraine-specific medication (AMSM) use in migraine patients with and without aura, an analysis of clinical trial data found.
“Findings of this post hoc secondary analysis support the safety and efficacy of erenumab in patients with migraine with or without a history of aura,” Messoud Ashina, MD, PhD, of University of Copenhagen in Denmark, and co-authors wrote in JAMA Neurology.
“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,” Ashina and colleagues continued. “Among patients who used AMSM, monthly AMSM days were reduced. These clinical responses were maintained in the longer term, with a treatment time frame ranging from 1 to 1.25 years and up to 5 years in some cases.”
“The safety profile of long-term erenumab treatment was similar in patients with and without a history of aura and was comparable to that of placebo over 12 weeks, with no increased emergence of adverse events over time,” the researchers added.
“Migraine is a major public health problem and better treatment options are still needed, both for acute and preventive treatments,” noted Jakob Moeller Hansen, MD, PhD, of Rigshospitalet Danish Headache Center, who was not involved with the study, in an email to BreakingMED.
“Our understanding of different disease mechanisms in migraine, with and without aura, could ideally lead to more precise treatments tailored to fit the migraine type,” Hansen continued.
“Studies like the paper from Ashina et al are useful for clinicians because we get the data for these important migraine subtypes,” he added. “This allows us to better advise people with migraine.”
Erenumab is a humanized anti-CGRP receptor monoclonal antibody approved for migraine prevention in 2018. A drug safety labeling change in 2021 added a precaution that new-onset or worsening of pre-existing hypertension may occur with the drug.
Migraine with aura confers elevated vascular risk compared with migraine without aura, and people who have aura may respond differently to acute migraine therapy. A 2019 review noted that migraine with aura differs from migraine without aura in having different heritability, greater association with stroke, and different imaging findings.
The post hoc analysis included four trials conducted between August 2013 and November 2019 of adults ages 18-65 with episodic or chronic migraine. All participants were randomized to receive either erenumab (one or more doses of 70 mg or 140 mg subcutaneously, once monthly) or placebo during a double-blind treatment phase, open-label, or dose-blinded active treatment phases. In addition to MMD and AMSM outcomes, safety end points were analyzed.
Overall, 2,682 patients were randomized and 1,400 (52.2%) received one or more doses of erenumab. The mean age was 41.7; 84.1% were women; and 91.0% were White.
“Multiple cardiovascular risk factors were more prominent in patients with versus patients without a history of aura including diabetes, history of hypertension, high blood pressure, high lipids, and body mass index of 30 or higher,” the authors noted.
Compared with placebo (n=1,043), results were determined for categories comprising combinations of four variables: aura (n=1,140) versus no aura (n=1,303) ; episodic versus chronic; dose 70 mg versus 140 mg; and two outcomes (MMDs, AMSM).
Compared with placebo, at week 12, least-squares mean differences in change from baseline during the double-blind portion of the analysis were as follows for the episodic migraine trials:
- MMD with aura: –1.1 (95% CI –1.7 to –0.6) for 70 mg, and –0.9 (95% CI –1.6 to –0.2) for 140 mg for migraine with aura.
- MMD without aura: –1.2 (95% CI –1.6 to–0.7) for 70 mg and –2.5 (95% CI, –3.2 to –1.8) for 140 mg.
- AMSM with aura: –0.9 (95% CI –1.4 to –0.3) for 70 mg and −1.3 (95% CI −2.0 to −0.5) for 140 mg.
- AMSM without aura: –1.3 (95% CI –1.8 to –0.8) for 70 mg and −2.4 (95% CI −3.1 to −1.8) for 140 mg.
In patients with chronic migraine, changes from baseline were:
- MMD with aura: –2.1 (95% CI –3.8 to –0.5) for 70 mg and –3.1 (95% CI –4.8 to –1.4) for 140 mg.
- MMD without aura: –2.7 (95% CI –4.1 to –1.3) for 70 mg and –2.1 (95% CI –3.5 to –0.7) for 140 mg.
- AMSM with aura: –2.4 (95% CI, –3.9 to –1.0) for 70 mg and −3.7 (95% CI −5.0 to −2.3) for 140 mg.
- AMSM without aura: –2.3 (95% CI –3.5 to –1.0) for 70 mg and −3.0 (95% CI −4.2 to −1.7) for 140 mg.
“Overall safety profiles were similar across treatment groups regardless of aura history,” Ashina and colleagues wrote. No unexpected safety findings were observed, and most reported adverse events were mild or moderate, they added.
For migraine patients without aura, 49.7% in the placebo group and 46.4% in the erenumab group reported an adverse event during the double-blind treatment phase. For those with a history of aura, the rate was 47.9% in the placebo group and 47.7% in the erenumab group.
“Discontinuations because of adverse events during the double-blind treatment phase were low in both subgroups but slightly higher in patients with a history of aura who received erenumab,” the authors noted.
“Treatment discontinuation because of adverse events remained low throughout the long-term analysis and was comparable between subgroups (2.5-2.7 per 100 patient-years),” they added. “Cardiovascular, cerebrovascular, and hypertension adverse event rates in the extension phases were low, with no differences among subgroups.”
The highest rates of adverse events seen in the open label phase were hypertension-related at 2.3% for those with and 2.2% for those without aura. Serious adverse events during the open label phase occurred in 4.7% of those with and 3.8% of those without aura.
The authors said their results may not be generalizable to patients from diverse racial and ethnic minority groups and people older than 65. In addition, people without history of aura had higher exposure to prior acute and preventive migraine medications.
Erenumab reduced monthly migraine days and acute migraine-specific medication use in patients with and without aura, an analysis of clinical trial data found.
The safety profile of long-term erenumab treatment was similar in patients with and without a history of aura.
Paul Smyth, MD, Contributing Writer, BreakingMED™
This study was funded by Amgen Inc.
Ashina reported being a consultant or scientific advisor for AbbVie, Allergan, Amgen, Eli Lilly, Lundbeck, Novartis, and Teva Pharmaceuticals; being a principal investigator for ongoing trials for AbbVie/ Allergan, Amgen, Eli Lilly, and Novartis; and receiving grants from Lundbeck Foundation, Novo Nordisk Foundation, and Novartis.
Hansen has received speaking fees from Lundbeck, Novartis, and Teva.
Cat ID: 35
Topic ID: 82,35,730,35,192,925