A phase 4, randomized, placebo-controlled trial found that erenumab, a calcitonin gene-related peptide receptor monoclonal antibody, was effective in achieving remission of medication overuse headache in patients with chronic migraine.
The study, published in JAMA Neurology, provided American Academy of Neurology class I evidence for erenumab as a preventive therapy in chronic migraine for medication overuse headache (MOH).
The trial, conducted at 67 centers across North America, Europe, and Australia from October 7, 2019, to November 2, 2022, included 584 adults with chronic migraine and nonopioid MOH with at least 1 prior preventive treatment failure. Participants were randomized 1:1:1 to receive monthly subcutaneous injections of erenumab 140 mg, erenumab 70 mg, or placebo for 24 weeks.
At month 6, 69.1% of participants in the erenumab 140 mg group achieved MOH remission, compared to 60.3% in the 70 mg group and 52.6% in the placebo group. The difference was statistically significant for the 140 mg dose (odds ratio [OR], 2.0) but not for the 70 mg dose (OR, 1.37).
Erenumab also significantly reduced acute headache medication days (AHMD). Mean change from baseline in monthly AHMD was -9.4 days for erenumab 140 mg (difference from placebo, -2.7) and -7.8 days for erenumab 70 mg (difference from placebo, -1.2), compared to -6.6 days for placebo.
Sustained MOH remission throughout the double-blind treatment period was achieved by 61.3% of participants in the 140 mg group (OR, 2.63) and 49.5% in the 70 mg group (OR, 1.62), compared to 37.6% in the placebo group.
The study also evaluated patient-reported outcomes, with results differing by region. In the non-EU region, improvements were seen in the Migraine Physical Function Impact Diary (MPFID) scores, showing reductions in physical impairment and impact on everyday activities for both erenumab doses compared to placebo.
In the EU region, changes in Headache Impact Test-6 (HIT-6) scores also favored erenumab treatment.
Safety outcomes were consistent with the known profile of erenumab. The most common adverse events in the combined erenumab group were constipation (15.2%) and COVID-19 (13.9%). Serious adverse events occurred in 1.5% of erenumab-treated participants, compared to 4.1% in the placebo group.
The study population had a mean age of 44 years, was predominantly female (82.5%), and had a mean of 20.8 monthly headache days at baseline. The most common type of MOH was from triptan (68.5%), followed by multiple drug intake (15.4%), simple analgesics/nonsteroidal anti-inflammatory drugs (8.4%), and combination analgesic (7.7%).
Baseline demographics and disease characteristics were balanced across treatment groups. All participants had prior migraine preventive medication use at baseline, with 67.6% having failed two or more preventive treatments. The exclusion of patients with opioid overuse and the potential selection bias due to erenumab's availability in some countries were noted as limitations.
The trial provided important data on the efficacy of erenumab in a challenging subgroup of chronic migraine patients with MOH, offering class I evidence for its use as a preventive therapy. The 24-week trial design and focus on MOH as a primary outcome were notable aspects of the study, although limitations such as patient selection bias were acknowledged.
The lead author reported personal fees from Amgen during the conduct of the study, as well as research funding, consultant/advisory board honoraria, speaker fees, and continuing medical education honoraria from numerous pharmaceutical companies and medical organizations outside the submitted work. Multiple other authors reported personal fees, research funding, and/or employment relationships with Amgen and other pharmaceutical companies.
