A recent phase 4 study has revealed that erenumab (Aimovig; Amgen) is effective in achieving remission of medication overuse headache (MOH) in patients with nonopioid chronic migraine (CM). The study, published in JAMA Neurology, provides class I evidence supporting the use of erenumab, a calcitonin gene-related peptide (CGRP) pathway inhibitor, in this patient population.
The parallel-group, randomized trial, led by Stewart Tepper, MD, included 584 participants with CM-MOH who had previously failed at least one preventive treatment. Participants were randomized to receive either erenumab 70 mg (n = 195), erenumab 140 mg (n = 195), or placebo (n = 194) once monthly for 24 weeks.
Study Design and Patient Characteristics
The study population primarily consisted of females (82.5%), with a mean age of 44 years. The most common categories of medication overuse at baseline were triptans (68.5%), multiple drugs not individually overused (15.4%), simple analgesics/nonsteroidal anti-inflammatory drugs (8.4%), and combination analgesics (7.7%).
Primary Endpoint: MOH Remission
The primary endpoint, absence of MOH at month 6, was defined as fewer than 10 mean monthly acute headache medication days (AHMD) or fewer than 14 mean monthly headache days over months 4, 5, and 6. Results showed that 69.1% of participants in the erenumab 140 mg group achieved MOH remission, compared to 60.3% in the erenumab 70 mg group and 52.6% in the placebo group. The odds ratio for the 140 mg group versus placebo was 2.01 (95% CI, 1.33-3.05; P <.001).
Secondary Endpoints: Reduction in AHMD and Impact on Daily Life
Patients in the erenumab 140 mg group, who had a baseline average monthly AHMD of 19.1 days, experienced a least square mean (LSM) reduction of 9.4 days (SD, 0.4; difference from placebo, –2.7; 95% CI, –3.9 to –1.6; P <.001). The 70 mg group, with a baseline AHMD of 18.6 days, saw an LSM reduction of 7.8 days (SD, 0.4; difference from placebo, –1.2; 95% CI, –2.4 to –0.1; P = .03). The placebo group had a baseline AHMD of 18.9 days with an LSM change of –6.6 days (SD, 0.4).
Improvements were also observed in physical impairment and impact on everyday activities, as measured by the MPFID. The change from baseline in mean physical impairment average domain scores was –10.6 for the 140-mg erenumab group (P = .08) and –11.8 for the 70-mg erenumab group (P = .01), compared to –8.5 in the placebo group. Similarly, the change from baseline in mean monthly average impact on everyday activities domain scores was –13.3 for the 140-mg erenumab group (P = .04) and –13.5 for the 70-mg erenumab group (P = .03), compared to –10.9 in the placebo group.
Headache Impact Test (HIT)-6 Scores and Monthly Migraine Days (MMDs)
Change from baseline in Headache Impact Test (HIT)-6 scores showed an LSM estimate of change during the double-blind treatment period of –8.8 for the erenumab 140 mg group (P <.001) and –6.2 for the erenumab 70 mg group (P = .09), compared to –5.0 in the placebo group.
The LSM estimate of change in monthly migraine days (MMDs) from baseline over months 4 to 6 was –9.0 for the erenumab 140 mg group (P < .001) and –7.5 for the erenumab 70 mg group (P = .01), compared to –6.0 in the placebo group.
Dose-Response Relationship
"MOH remission rates and MMD responses could be significantly influenced by dose with the findings of our present study suggesting a clear dose-response association in favor of the 140-mg dose of erenumab," Tepper et al noted. This observation aligns with previous analyses indicating that erenumab 140 mg may offer incremental benefit over 70 mg, particularly in difficult-to-treat migraine subpopulations.
Safety Profile
The incidence rates of adverse events were consistent with the known safety profile of erenumab in migraine. Patients in the active treatment arms experienced a greater rate of adverse drug reactions, such as constipation and injection site reactions, than those on placebo. No new treatment-emergent adverse events were observed in this study.
