Efficacy and safety of eptinezumab in adults with chronic migraine and medication-overuse headache who also received patient education: 24-week results of the randomized RESOLUTION trial

Abstract Background The phase 4 RESOLUTION trial showed that the first 12 weeks of treatment with eptinezumab, an anti-calcitonin gene-related peptide monoclonal antibody, reduced migraine frequency, severity, and disease burden, and improved quality of life (QOL) versus placebo in participants with chronic migraine (CM) and medication-overuse headache (MOH) who also received patient education. Here, we present 24-week eptinezumab efficacy and safety in the RESOLUTION trial. Methods RESOLUTION was a randomized, parallel-group, multinational clinical trial that included a 12-week double-blind, placebo-controlled period and a 12-week open-label extension period (OLE). Adults (18–75 years) with CM and MOH (excluding opioid-overuse headache) received a brief educational intervention about MOH at baseline and were randomized (1:1) to IV eptinezumab 100 mg or placebo. At Week 12, all participants received eptinezumab 100 mg. Measures used for primary and key secondary efficacy endpoints were also captured during the OLE: mean changes from baseline in monthly migraine days (primary endpoint: Weeks 1–4), monthly headache days, monthly days with acute medication use, average daily pain, and participants no longer meeting threshold criteria for CM nor MOH. Secondary endpoints (including patient-reported-outcomes [PROs] assessing disease-related burden and health-related QOL) and treatment-emergent adverse events (TEAEs) were also captured during the OLE. Results Of 608 participants randomized, 593 (97.5%) were treated with eptinezumab in the OLE, and 584/608 (96.1%) completed the trial. Reductions in migraine frequency and active CM/MOH diagnosis, and improvements across multiple PROs observed in post hoc analyses during the placebo-controlled period were sustained during the OLE for participants initially treated with eptinezumab, with similar levels of improvement gained for those initially receiving placebo. The proportion of participants with TEAEs in the OLE was similar between eptinezumab–eptinezumab and placebo–eptinezumab treatment sequence groups (30% vs 34%); no new safety signals were identified. Conclusions In participants with CM and MOH who received patient education, reductions in disease burden and improvements in QOL during the first 12 weeks with eptinezumab treatment were sustained for up to 24 weeks following a second eptinezumab infusion, with similar improvements observed in participants switched from placebo to eptinezumab. Eptinezumab was generally well tolerated, with no new safety signals. Trial registration ClinicalTrials.gov Identifier: NCT05452239 (https://clinicaltrials.gov/study/NCT05452239); EudraCT Number: 2021-003049-40 (https://www.clinicaltrialsregister.eu/ctr-search/search?query=2021-003049-40)