Migraine Patients Achieve Remission of Medication Overuse Headaches with Erenumab

A new study revealed monthly injections of erenumab 140 mg were effective in achieving remission of non-opioid medication overuse headache in patients with chronic migraine within 6 months.¹

“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 and medication overuse headaches] (nonopioid),” wrote investigators, led by lead investigator Stewart J, Tepper, MD, from the New England Institute for Neurology and Headache at Stamford, Connecticut.

Overusing non-opioid medications can invoke headaches among patients with chronic migraine. This population experiences a substantial burden on functioning, pain interference, and quality of life. As of now, a consensus treatment for chronic migraine and medication overuse headaches does not exist.

“Those patients with medication overuse headache (MOH) have higher disability and a significant unmet clinical need,” Tepper said in a statement.²

Investigators sought to assess the efficacy and safety of erenumab for chronic migraine and medication overuse headaches.¹ The team conducted a randomized, double-blind, parallel-group, placebo-controlled trial at 67 centers across North America, Europe, and Australia from October 7, 2019, to November 2, 2022. The primary analysis was conducted in January 2023 using data from December 1, 2022, on the double-blind treatment period.

The sample included 620 adults with chronic migraine and medication overuse headaches who failed to reach remission with ≥ 1 preventive treatment. The most overused medications at baseline included triptan (68.5%), multiple drugs not individually overused (15.4%), simple analgesics/nonsteroidal anti-inflammatory drugs overuse (8.4%), and combination analgesic overuse (7.7%).

The non-opioid and opioid cohorts had 584 and 36 participants, respectively. Those in the non-opioid cohort had a mean age of 44 years and 482 females (82.4%), and the baseline demographic and disease characteristics were comparable between the cohorts.

Investigators evaluated erenumab at 70 mg or 140 mg, compared to placebo, once monthly for 4 weeks to see if patients will reach remission on headaches caused by medication overuse. The primary endpoint was chronic migraine and medication overuse headache remission at month 6. Secondary endpoints included change from baseline in mean monthly acute headache medication days at month 6 and sustained remission throughout the double-blind treatment period.

At month 6, 69.1% of participants in the erenumab 140 mg group (odds ratio [OR], 2.01; 95% confidence interval [CI], 1.33 to 3.05; P < .001) and 60.3% in the erenumab 70 mg group (OR, 1.37; 95% CI, 0.92 to 2.05; P = .13) achieved medication overuse headache remission, compared with 52.6% of participants on placebo.

Investigators also observed both erenumab groups had reduced acute headache medication days compared with placebo. The change from baseline in average monthly acute headache medication days was reduced – 9.4 days in the erenumab 140 mg group (difference from placebo, –2.7; 95% CI, –3.9 to –1.6; P < .001) and -7.8 days in the erenumab 70 mg group (difference from placebo, –1.2; 95% CI, –2.4 to –0.1; P = .03). However, placebo only reduced -6.6 days.

Remission was sustained throughout the double-blind treatment period in 61.3% and 49.5% of participants in the erenumab 140 and 70 mg cohorts, respectively, and 37.6% on placebo.

An ad hoc sensitivity analysis shifted the definition of chronic migraine and medication overuse headaches to mean monthly headaches ≤ 14 days and mean monthly acute headache medication ≤ 10 days over months 4, 5, and 6. This analysis produced similar findings, showing 53.6% of participants on erenumab 140 mg (P < .001), 45.9% on erenumab 70 mg (P = .06) achieved remission compared with 36.6% on placebo.

Overall, the injections appeared safe, and the adverse events were consistent with the known safety profile of erenumab. Among participants on erenumab, the incidence of treatment-emergent adverse events was 66.8%. The most reported adverse events were constipation (15.2%) and COVID-19 (13.9%), injection site pain (5.2%), nasopharyngitis (5.2%), and insomnia (4.6%).

“The change for clinical care will be that practitioners can start patients with [chronic migraine and medication overuse headaches] on erenumab and expect a likelihood of [chronic migraine and medication overuse headaches] remission for most without other interventions, such as planned wean, inpatient detoxification, or behavioral therapies,” Tepper said.² “This will simplify and improve care of [chronic migraine and medication overuse headaches] patients.”

References

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}
2. ^{Efficacy and safety of erenumab for nonopioid medication overuse headache in chronic migraine. EurekAlert! September 16, 2024. https://www.eurekalert.org/news-releases/1057866. Accessed September 18, 2024.}