Eptinezumab With Patient Education for Chronic Migraine and Medication-Overuse Headache: The Randomized,...

Medication-overuse headache (MOH) commonly co-occurs with and complicates chronic migraine (CM). This trial evaluated efficacy and safety of eptinezumab, an anti-calcitonin gene-related peptide monoclonal antibody for migraine prevention-combined with a standardized brief educational intervention (BEI)-in adults with CM and MOH. We report results from the 12-week placebo-controlled period, of which weeks 1-4 was the primary time point.

The phase 4, double-blind, placebo-controlled RESOLUTION trial was conducted at 76 specialist clinics across 11 countries. Eligible participants were adults diagnosed with CM and MOH and were randomized 1:1 to eptinezumab 100 mg IV with BEI or placebo IV with BEI. The primary end point was mean change from baseline in monthly migraine days (MMDs; weeks 1-4). Key secondary end points (multiplicity-controlled) included changes from baseline in monthly headache days, monthly days with acute migraine medication use, and average daily pain, as well as fulfillment of thresholds defining CM and MOH. Treatment-emergent adverse events (TEAEs) were assessed.

Between July 2022 and March 2025, 608 participants were randomized, and 596 (98%) completed the placebo-controlled period. Of 604 participants treated, 517 (86%) were female and 87 (14%) were male; the mean age was 45.5 years (SD 12.0). The primary end point, mean change from baseline in MMDs (weeks 1-4), favored eptinezumab with BEI vs placebo with BEI (-6.9 vs -3.7; group difference -3.2; 95% CI -4.2 to -2.2; p < 0.0001). All key secondary end points showed statistically significant improvements with eptinezumab with BEI vs placebo with BEI; the greater reductions in disease burden observed during weeks 1-4 were sustained through weeks 1-12. The proportion of participants with TEAEs was similar with eptinezumab (41.9%) and placebo (36.9%); no new safety signals were identified.

In adults with CM and MOH who also received patient education, eptinezumab was statistically superior to placebo on the primary and all key secondary end points, reducing disease burden as early as weeks 1-4 and throughout weeks 1-12. Eptinezumab was generally well tolerated, with no new safety signals identified. Together, data from this trial indicate that eptinezumab in combination with patient education is an effective treatment for reducing disease burden in patients living with CM complicated by medication overuse.

ClinicalTrials.gov Identifier: NCT05452239 (clinicaltrials.gov/study/NCT05452239); EudraCT Number: 2021-003049-40 (clinicaltrialsregister.eu/ctr-search/search?query=2021-003049-40); EU CTR Number: 2024-510729-24-00 (euclinicaltrials.eu/search-for-clinical-trials/?lang=en&EUCT=2024-510729-24-00). EudraCT Number obtained: May 25, 2021. ClinicalTrials.gov Identifier obtained: July 6, 2022. First patient enrolled: July 1, 2022.

This clinical trial provides Class I evidence that eptinezumab with patient education is superior to placebo with patient education in reducing MMDs in adults with CM and MOH.