Erenumab reduced migraines in patients who didn't respond to other treatments, industry-funded study found

Erenumab was efficacious in patients with episodic migraine who previously did not respond to or tolerate between two and four previous preventive treatments, an industry-funded study found.

The trial included adult patients at 59 sites in 16 countries who had a history of episodic migraine with or without aura for at least 12 months and migraines for an average of 4 to 14 days per month during the three months before screening. Patients had previously tried two to four preventive treatments with lack of success in terms of efficacy, tolerability, or both. They were randomly assigned to receive either erenumab, 140 mg (via two 70-mg injections), or placebo, subcutaneously every four weeks for 12 weeks. Randomization was stratified by monthly frequency of migraine headache (4 to 7 migraine-days per month vs. 8 to 14 migraine-days per month).

The primary endpoint was the proportion of patients in whom the mean number of monthly migraine-days during weeks 9 to 12 decreased by 50% or more. Efficacy was measured in the full analysis set, which included all randomly assigned patients who started their assigned treatment and completed at least one monthly migraine-day measurement post-baseline. Safety and tolerability were assessed by record of adverse events and by physical examination, assessment of vital signs, clinical laboratory assessments, and electrocardiography. The study results were published by The Lancet on Oct. 22.

Two hundred forty-six participants were included in the study, 121 in the erenumab group and 125 in the placebo group. At week 12, 36 (30%) patients in the erenumab group met the primary endpoint, compared with 17 (14%) in the placebo group (odds ratio [OR], 2.7; 95% CI, 1.4 to 5.2; P=0.002).A significantly greater proportion of patients in the erenumab group than in the placebo group also had a 50% or greater reduction in monthly number of migraine-days during weeks 0 to 4 and weeks 5 to 8. At 12 weeks, 14 (12%) of patients in the erenumab group and five (4%) in the placebo group had a 75% or greater reduction in the monthly number of migraine-days (OR, 3.2; 95% CI, 1.1 to 9.0; P=0.025).

For weeks 9 to 12, the active treatment group also had significant improvements in all secondary endpoints, including monthly days with migraine and monthly migraine-specific medication days, compared with the placebo group. Differences in efficacy between erenumab and placebo were apparent for all secondary outcomes at week 4. Erenumab and placebo had similar tolerability and safety profiles. Injection-site pain, the most frequent treatment-emergent adverse event, occurred in seven (6%) participants in both groups.

Erenumab belongs to a new class of drugs called calcitonin gene-related peptide receptor (CGRP-R) antagonists. CGRP is believed to play an important role in the generation of pain during migraine attacks by facilitating cellular events that contribute to sensitization of neurons involved in nociceptive transmission. Erenumab is thought to reduce the number of migraine attacks by blocking CGRP-R receptors on blood vessels.

Erenumab might be an option for patients with difficult-to-treat migraine who have high unmet needs and few treatment options, the authors concluded. An accompanying editorial noted that migraine patients in whom treatments are not successful often lose confidence in their care. Migraine-specific preventive therapies involving calcitonin gene-related peptide hold the promise of improved efficacy and tolerability compared with treatments that were initially developed for other conditions, the editorialists said. “These are encouraging times for patients with migraine, and for the clinicians who care for them,” the editorialists wrote.

An article in the October 2018 ACP Internist reviewed the pros and cons of new drugs for migraine prevention.