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Erenumab Induces Remission in Chronic Migraine Medication Overuse Headache
Erenumab 140 mg safely and effectively induced remission in nonopioid MOH within 6 months in individuals for whom other preventive medications had failed.
The migraine preventive medication erenumab 140 mg was found safe and effective in inducing remission of nonopoioid medication overuse headaches (CM-MOH) in adults with chronic migraine within 6 months, according to findings published online in JAMA Neurology this week. Remission was sustained among more than half (61.3%) of the participants with MOH receiving erenumab compared with just slightly more than one-third (37.6%) of those who were treated with placebo.1
“To our knowledge, this study is the first controlled trial to provide American Academy of Neurology class I evidence of beneficial effects of a migraine preventive treatment in patients with [chronic migraine and medication overuse headaches] (nonopioid),” wrote investigators, led by Stewart J. Tepper, MD, from the New England Institute for Neurology and Headache, in Stamford, Connecticut.1
Disability is higher among individuals with migraine and MOH and yet currently there is no consensus on treatment for the condition, creating a significant unmet medical need, they added.
Erenumab (Aimovig; Amgen) is a calcitonin gene-related peptide antagonist and was the first in this class to be approved (May 2018). The medication is given once monthly by self-injection. In a subgroup analysis of a pivotal phase 3 registration trial monthly headache days were significantly reduced among participants who met criteria for MOH at study baseline. These participants more often reverted to non-MOH status compared with placebo-treated participants, study authors wrote. Given the limited knowledge of the efficacy of CGRP inhibitor efficacy based on this and other previous randomized trials, Tepper and colleagues designed the current investigation to assess the efficacy and safety of erenumab in a population specifically with chronic migraine MOH.
The phase 4 study
The phase 4 prospective, randomized, double-blind, parallel-group, placebo-controlled trial was conducted between October 7, 2019, and November 2, 2022, across North America, Europe, and Australia. The primary analysis was conducted in January 2023 using data from December 1, 2022, which contains the complete dataset from the study’s double-blind treatment period.
A cohort of 620 adults met the eligibility requirements: age 18 years or older and younger than 65 years and chronic migraine and MOH without remission despite previous treatment with one or more preventive medications. Of this group, 584 comprised the group for primary analysis, ie, had no history of treatment with opioids.
Participants were randomly assigned to receive erenumab 70 mg, erenumab 140 mg, or placebo , once monthly for 24 weeks. Tepper et al designated MOH remission at 6 months at the primary endpoint. They specified several secondary endpoints as well: change from baseline in mean monthly acute headache medication days (AHMD) at month 6 and sustained MOH remission throughout the double-blind treatment period. Evaluation of erenumab safety evaluated adverse events (AEs) and changes in vital signs.
FINDINGS
The study cohort was predominantly women (82.5%) and had an average age of 44 years. The groups were balanced across baseline demographics and disease characteristics, according to the study. At study baseline the most common classes of medication overused were triptans (68.5%), multiple drugs not individually overused (15.4%), simple analgesics/nonsteroidal anti-inflammatory drugs (8.4%), and combination analgesics (7.7%).
At month 6, Tepper and team reported, 69.1% of participants in the erenumab 140 mg group (odds ratio [OR], 2.01; 95% CI, 1.33 to 3.05; P < .001) and 60.3% in the erenumab 70 mg group (OR, 1.37; 95% CI, 0.92 to 2.05; P = .13) reached MOH remission, compared with 52.6% of participants who received placebo.
Remission was predefined as less than 10 mean monthly acute headache medication days (AHMD) with the measure reduced among both groups receiving erenumab compared with placebo. The investigators found a change from baseline in mean monthly AHMD of
- – 9.4 days in the erenumab 140 mg group (difference from placebo, –2.7; 95% CI, –3.9 to –1.6; P < .001)
- – 7.8 days in the erenumab 70 mg group (difference from placebo, –1.2; 95% CI, –2.4 to –0.1; P = .03).
The reduction reported for the placebo-treated participants was –6.6 days.
Remission of MOH was sustained throughout the double-blind treatment period in 61.3% and 49.5% of participants in the erenumab 140 and 70 mg cohorts, respectively, and in 37.6% of participants taking placebo.
For an ad hoc sensitivity analysis, the absence of MOH at 6 months was defined based on both mean monthly headache days less than 14 days and mean monthly AHMD fewer than 10 days during months 4, 5, and 6 of the double-blind treatment period. Findings from analysis were similar to the primary analysis, according to the study. The researchers reported that 53.6% of participants on erenumab 140 mg (P < .001) and 45.9% on erenumab 70 mg (P = .06) achieved remission compared with 36.6% on placebo.
Treatment with erenumab was judged as safe, and the treatment-emergent AEs were consistent with the known safety profile of erenumab. AE incidence among the erunamab-treated participants was 66.8%, the most commonly reported being constipation (15.2%), COVID-19 (13.9%), injection site pain (5.2%), nasopharyngitis (5.2%), and insomnia (4.6%).
Tepper, commenting on the potential for change in clinical care based on the study findings, suggested that for a patient with migraine and MOH, initial use of erenumab may lead to remission as monotherapy and obviate the need for other interventions, “such as planned wean, inpatient detoxification, or behavioral therapies.”2 He added that the strategy could both simplify and improve care for individuals with migraine and MOH.
