Nonopioid Medication Overuse Headache Remission Observed With Erenumab

Stewart Tepper, MD

In a recently published phase 4 study (NCT03971071), treatment with 140 mg injections of erenumab (Aimovig; Amgen) resulted in effective medication overuse headache (MOH) remission among patients with nonopioid chronic migraine (CM)-MOH within 6 months. To the authors knowledge, this was the first controlled trial to provided American Academy of Neurology class I evidence of beneficial effects of a migraine preventive treatment in patients with nonopioid CM-MOH.

Led by Stewart Tepper, MD, vice president at the New England Institute for Neurology and Headache in Stamford, Connecticut, this parallel-group, randomized trial featured 584 participants with CM-MOH who had 1 or more preventive treatment failure. In the study, patients were randomly assigned to either erenumab 70 mg (n = 195), 140 mg (n = 195), or placebo (n = 194) once monthly for 24 weeks. Erenumab, an anti-calcitonin gene-related peptide (CGRP) pathway inhibitor, has been approved as a treatment for CM since 2018.

Coming into the trial, the most commonly observed categories of medication overuse at baseline were 400 for triptan overuse (68.5%), 90 for overuse of multiple drugs not individually overused (15.4%), 49 for simple analgesics/nonsteroidal anti-inflammatory drugs overuse (8.4%), and 45 for combination analgesic overuse (7.7%). The study was primarily comprised of females (82.5%) and the mean age of participants was 44 years.

Absence of MOH at month 6 was the primary end point of the study and was defined by mean monthly acute headache medication days (AHMD) less than 10 days over months 4, 5, and 6 or mean monthly headache days less than 14 days over months 4,5, and 6 of the double-blind treatment period where AHMD include any electronic diary day in which an acute headache medication intake is reported. Over months 4 through 6, 69.1% of participants on erenumab 140 mg (OR, 2.01; 95% CI, 1.33-3.05; P <.001 vs placebo), and 60.3% of the erenumab 70 mg group (OR, 1.37; 95% CI, 0.92-2.05; P = .13 vs placebo) achieved MOH remission compared with 52.6% of those on placebo.

In the erenumab 140 mg group, which entered the study with a baseline average monthly AHMD of 19.1 days, these patients saw a least square mean (LSM) estimate reduction of 9.4 days (SD, 0.4; difference from placebo, –2.7; 95% CI, –3.9 to –1.6; P <.001). In the erenumab 70 mg group, which had a baseline AHMD of 18.6 days, patients saw a LSM reduction of 7.8 days (SD, 0.4; difference from placebo, –1.2; 95% CI, –2.4 to –0.1; P = .03). For context, the placebo group entered with a baseline AHMD of 18.9 days with an LSM change of –6.6 days (SD, 0.4).

The change from baseline in mean physical impairment average domain scores (SE) by MPFID, a key secondary end point, was –10.6 (SE, 0.9) from a baseline of 27.6 for the 140-mg erenumab group (P = .08) and –11.8 (SE, 0.9) from a baseline of 31.3 for the 70-mg erenumab group (P = .01). In contrast, the placebo group had changes of –8.5 (SE, 0.9) from a baseline of 27.6. The change from baseline in mean monthly average impact on everyday activities domain scores by MPFID was –13.3 (SE, 0.8) from a baseline of 29.9 for the 140-mg erenumab group (P = .04) and –13.5 (SE, 0.9) from a baseline of 33.1 for the erenumab, 70 mg group (P = .03), compared with –10.9 (SE, 0.8) down from a baseline of 30.3 in the placebo group.

Change from baseline in Headache Impact Test (HIT)-6 scores was also considered a secondary outcome assessment. In the study, investigators recorded an LSM estimate of change during the double-blind treatment period of –8.8 (SE, 0.5) from a baseline of 64.2 for the erenumab 140 mg group (P <.001), and –6.2 (SE, 0.5) from a baseline of 64.8 for the erenumab 70 mg group (P = .09), compared with –5.0 (SE, 0.5) from a baseline of 64.2 in the placebo group.

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The trial also assessed change in monthly migraine days (MMDs) over months 4 to 6 as an exploratory end point. Overall, the LSM estimate of MMD change from baseline over months 4 to 6 was –9.0 (SE, 0.4) from a baseline of 18.6 days in the erenumab 140 mg, group (P < .001) and –7.5 (SE, 0.4) from a baseline of 19.2 MMDs in the erenumab 70 mg, group (P = .01), as compared with –6.0 (SE, 0.4) from a baseline of 18.6 MMDs in the placebo group.

Tepper et al noted that "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. This observation is further substantiated by a previously reported analysis that indicated that erenumab, 140 mg, is likely to offer incremental benefit over 70 mg, specifically within the context of difficult-to-treat migraine subpopulations."

In terms of safety, the participants incidence rates of adverse events were consistent with the known safety profile of erenumab in migraine. Patients in the active arm experienced a greater rate of adverse drug reactions, such as constipation and injection site reactions, than those on placebo. Notably, no new treatment-emergent adverse events were observed in this study.

REFERENCE
1. Tepper SJ, Dodick DW, Lanteri-Minet M, et al. Efficacy and Safety of Erenumab for Nonopioid Medication Overuse Headache in Chronic Migraine: A Phase 4, Randomized, Placebo-Controlled Trial. JAMA Neurol. Published online September 16, 2024. doi:10.1001/jamaneurol.2024.3043.