Efficacy and safety of eptinezumab in patients with chronic migraine and medication-overuse headache: a randomized, double-blind, placebo-controlled study

Abstract

Background: For some people with migraine, despite taking greater amounts of acute headache medication (AHM), they develop an increase in monthly headache days. This cycle of increasing headache days, and in turn AHM use, can lead to a secondary headache disorder called medication-overuse headache (MOH). Preventive medications can prevent migraine from occurring and reduce reliance on AHMs, thereby preventing the cycle of MOH. This study was performed to evaluate the efficacy and safety of eptinezumab to prevent migraine/headache in a mainly Asian patient population with a dual diagnosis of chronic migraine and MOH.

Methods: SUNLIGHT was a phase 3, multicenter, double-blind, parallel-group, placebo-controlled trial. Patients aged 18-75 years with ≥ 8 migraine days/month and a diagnosis of MOH were randomly allocated (1:1) to one of two treatment groups: eptinezumab 100 mg or placebo. Monthly migraine days (MMDs) were captured using a daily electronic diary; the change from baseline in the number of MMDs over Weeks 1-12 was the primary efficacy endpoint.

Results: Patients were randomized to eptinezumab 100 mg (n = 93) or placebo (n = 100). Over Weeks 1-12, eptinezumab reduced mean MMDs more than placebo (difference between treatments was -1.2; p = 0.1484). Differences between treatment groups with p-values below 0.05 favoring eptinezumab were observed in 3 out of the 6 key secondary endpoints.

Conclusion: All endpoints numerically favored eptinezumab treatment when compared to placebo; however, this study did not meet its primary endpoint and is therefore negative. No new safety signals were identified in this study, like previous reports that confirmed the safety and tolerability of eptinezumab treatment.

Trial registration: ClinicalTrials.gov identifier: NCT04772742 (26/02/2021).

Keywords: Anti-CGRP; Chronic migraine; Eptinezumab; Medication-overuse headache; Preventive migraine treatment.

Fig. 1

Patient disposition (placebo-controlled period). *Completed and withdrawn data refer to the number of patients completing or withdrawing in the placebo-controlled period. **Three patients from the eptinezumab group were excluded from the full analysis set because no post-baseline primary endpoint data were contributed. AE, adverse event

Fig. 2

Change from baseline in mean MMDs (A) Weeks 1–12 and (B) 4-week intervals (FAS). The estimated means, mean differences from placebo, and 95% confidence intervals are from a mixed model for repeated measures with month (Weeks 1–4, Weeks 5–8, Weeks 9–12), region, stratification factor (monthly headache days at baseline: < 20/ ≥ 20), and treatment as factors, baseline score as a continuous covariate, treatment-by-month interaction, baseline score-by-month interaction, and stratum-by-month interaction. Data represent mean ± standard error. FAS, full analysis set; MMDs, monthly migraine days

Fig. 3

Patients with ≥ 50% and ≥ 75% reduction from baseline in MMDs over Weeks 1–12 (FAS). The 50% and 75% response variables across the three 4-week intervals are calculated as the average percentage change in MMDs (based on the available monthly values of MMDs). The comparison is based on logistic regression model including baseline MMDs as a continuous covariate, and treatment and stratification factor (monthly headache days at baseline: < 20/ ≥ 20) as factors. If the MMD value is missing for a given month, the responder status is derived based on the available values. n indicates the number of patients with observations. Data represent mean percentages. FAS, full analysis set; MMD, monthly migraine days; MRR, migraine responder rate

Fig. 4

Patient Global Impression of Change (A) and patient-identified most bothersome symptom (B) scores (FAS). The model includes the following fixed effects: visit, region, stratification factor (monthly headache days at baseline: < 20/ ≥ 20), and treatment as factors, treatment-by-visit interaction, and stratum-by-visit interaction. The PGIC and the PI-MBS are ranked on a scale of 1–7, and the lower the score the higher the clinical improvement. Patients could rate their change on the PGIC and PI-MBS scale as “Very much improved”, “much improved”, “minimally improved”, “no change”, “minimally worse”, “much worse”, or “very much worse”. Data represent mean ± standard error. FAS, full analysis set; PGIC, Patient Global Impression of Change; PI-MBS, patient-identified most bothersome symptom