Managing Medication Overuse Headache in Chronic Migraine

Monthly erenumab injections can safely and effectively achieve medication overuse headache remission in patients with nonopioid chronic migraine medication overuse headaches within 6 months, according to research published in JAMA Neurology.¹

It is not uncommon for patients with chronic migraine to overuse acute medications, leading to medication overuse headaches—a secondary headache disorder “defined by sustained overuse of acute headache medications” with worsening of a preexisting headache or development of a new type of headache associated with medication overuse. In chronic migraine, medication overuse headaches have been associated with an increased risk of preventive treatment failure, as well as stronger associations with psychiatric comorbidities, increased migraine-related disability, higher levels of health care utilization, and an overall decrease in quality of life.

In the current study—a phase 4, randomized, double-blind, parallel-group, placebo-controlled clinical trial (NCT03971071)—investigators evaluated the efficacy and safety of erenumab in adults with chronic migraine, with or without aura, for at least 12 months, with a concomitant diagnosis of medication overuse headache and a history of at least 1 preventive treatment failure. The primary study endpoint was absence of medication overuse headache at month 6.

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The cohort included 482 women and 201 men. At baseline, mean monthly headache days were 20.8±3.9 and mean acute headache medication use days were 18.9±4.2 days. The most common medications included triptans, simple analgestics/nonsteroidal anti-inflammatory drugs, and combination analgesics.

From months 4 to 6, 69.1% of participants receiving 140 mg erenumab and 60.3% of patients receiving 70 mg erenumab achieved medication overuse headache remission, compared with 52.6% of the placebo group (OR, 2.01, 1.37 in each treatment group, respectively). Reduction of both acute headache medication use days and rates of sustained medication overuse headache remission were higher in the erenumab group vs placebo.

Throughout the double-blind treatment period, medication overuse headache remission was sustained in 6.13% and 49.5% of the erenumab patients (140 mg and 70 mg, respectively) vs 37.6% of the placebo group.

Results of an ad hoc sensitivity analysis indicated that 53.6% and 45.9% of the 140 mg and 70 mg erenumab groups achieved medication overuse headache remission, vs 36.6% of the placebo group. Absence of medication overuse at month 6 was achieved by 59.3% and 49% of each group, vs 40.2% of the placebo group.

Incidence rates of adverse events were consistent with the known safety profile of erenumab in migraine. Most adverse events were mild to moderate in severity, and included constipation, injection site pain, nasopharyngitis, and insomnia. Six participants reported serious adverse events.

Study limitations include the study design, which was not intended to evaluate erenumab safety and efficacy outside of the context of migraine, limiting generalizability of results.

“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 medication overuse headache],” investigators concluded.

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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. 2024;3243043. doi:10.1001/jamaneurol.2024.3043