In a recent study of 6 monthly injections of 140 mg erenumab (Aimovig, Amgen), most patients with chronic migraine and nonopioid medication overuse headache (MOH) achieved remission. Published online in JAMA Neurology, the study is the first prospective, double-blind, randomized, placebo-controlled attempt to investigate patients with chronic migraine and MOH related to nonopioid medications, according to lead author Stewart J. Tepper, MD, and his coauthors.
Dr. Stewart J. Tepper
Prior Studies Did Not Focus on MOH
Several prior phase 2 and 3 trials of calcitonin gene-related peptide (CGRP) ligand or receptor inhibitors that have been FDA-approved for migraine prevention have been performed. These drugs include erenumab, fremanezumab (Ajovy, Teva), galcanezumab (Emgality, Lilly), and eptinezumab (Vyepti, Lundbeck), for patients with and without medication overuse, said Alan M. Rapoport, MD, who was not involved with the new study. Dr. Rapoport is a clinical professor of neurology at the David Geffen School of Medicine of the University of California, in Los Angeles; past president of the International Headache Society; and founder and director emeritus of The New England Center for Headache in Stamford, Connecticut.
“But we could not call them patients with MOH because they weren’t studied prospectively, so that they had medication overuse according to International Classification of Headache Disorders (ICHD-3) criteria,” said Dr. Rapoport.
Dr. Alan M. Rapoport
Phase 4, Randomized, Placebo-Controlled Trial
In the present clinical trial, investigators enrolled 584 patients with nonopioid MOH and history of failing at least one preventive treatment. After a 4-week baseline phase, researchers randomized patients 1:1:1 to 6 months’ treatment with erenumab 70 mg, erenumab 140 mg, or placebo.
Investigators defined remission as either of the following through months 4-6:
- < 10 mean monthly acute headache medication days per month (AHMD)
- < 14 mean monthly headache days (MHD)
In the primary analysis, 69.1% of patients in the 140 mg cohort achieved remission (P < .001) versus placebo. Remission rates in the 70 mg and the placebo cohorts were 60.3% (P < .13) and 52.6%, respectively. AHMD for the 140-mg, 70-mg, and placebo groups fell by 9.4, 7.8, and 6.6 days per month, respectively. Migraine Physical Function Impact Diary (non-EU sites) and Headache Impact Test-6 (EU sites) scores also showed greater improvement for patients treated with erenumab.
No new safety signals emerged, although erenumab-treated participants experienced 2-2.5 times as much COVID-19 disease.
Regarding the primary endpoint, said Dr. Rapoport, the 70-mg dose might also have yielded statistically significant improvement over placebo with a larger sample size. “I have seen that the higher dose of erenumab can be superior for efficacy than the lower in some of the double-blind trials,” he said. The 52.6% placebo response rate was rather high, he added, but not necessarily higher than in other migraine prevention trials.
“Placebo is a type of treatment,” Dr. Rapoport said. “It’s not as strong as the actual medication, which is specific for prevention, but it does work on the brain to some extent.”
He was more concerned, however, that authors did not counsel study patients about reducing or discontinuing their overused medications in a unified manner. Rather, it was left to individual investigators’ discretion, in different countries, as to whether to educate patients about the harms of medication overuse. “The fascinating aspect of this paper was that no patient was asked to detoxify from the overused medication,” said Dr. Rapoport, “and yet so many patients no longer had MOH at 6 months.”