AbstractObjectiveThis post hoc analysis of the PREVAIL study explored the effectiveness of eptinezumab for up to 2 years of open‐label treatment in the subgroup of patients with chronic migraine who had a confirmed diagnosis of medication‐overuse headache (MOH) at screening.BackgroundMOH is a disabling and costly secondary headache disorder characterized by increased headache frequency and/or severity with increased acute headache medication use. Eptinezumab, an anti–calcitonin gene‐related peptide monoclonal antibody, reduces headache frequency, severity, and associated disability and improves functioning and health‐related quality of life as a preventive migraine therapy; short‐term benefits in patients with concurrent MOH have also been reported.MethodsParticipants received up to eight quarterly intravenous infusions of eptinezumab 300 mg in the phase 3, single‐arm, open‐label PREVAIL study. Safety and patient‐reported outcome measures (Migraine Disability Assessment [MIDAS], 6‐item Headache Impact Test [HIT‐6], patient‐identified most bothersome symptom [PI‐MBS], Patient Global Impression of Change [PGIC], and 36‐item Short‐Form Health Survey [SF‐36]) were conducted at predefined intervals. Patients were observed up to 20 weeks after their last infusion (Week 104).ResultsA total of 49/128 (38.3%) patients enrolled in PREVAIL had an MOH diagnosis at screening. In the MOH subgroup, long‐term eptinezumab treatment was associated with reductions in headache frequency (43/49 [87.8%] patients reported ≥50% reduction in MIDAS‐derived headache days at ≥1 visit), severity (2.2‐point reduction [on a 10‐point scale]), disability (mean MIDAS total score reduction of 51.9 points), and impact (mean HIT‐6 total score reduction of 9.7 points) at Week 104. Most patients described a “much improved” or “very much improved” status by Week 48 (PI‐MBS, 31/46 [67.4%]) and Week 104 (PGIC, 31/36 [86.1%]). Health‐related quality of life improvements in the SF‐36 were also observed.ConclusionEptinezumab preventive therapy in patients with chronic migraine showed benefits that extended to the subset of patients with concomitant MOH.