Document Type

Article

Publication Date

5-1-2026

Comments

This article is the author’s final published version in Cephalalgia, Volume 46, Issue 5, 2026, Article number 03331024261451427.

The published version is available at https://doi.org/10.1177/03331024261451427. Copyright © International Headache Society 2026.

 

Abstract

AimTo evaluate 48-month real-world outcomes of eptinezumab users in chronic migraine (CM), including longitudinal effectiveness, treatment persistence, reasons for discontinuation, and post-discontinuation anti-calcitonin gene-related peptide (CGRP) treatment patterns.MethodsWe conducted a retrospective cohort study of 112 CM subjects initiating eptinezumab at a tertiary headache center between 2019 and 2021. Monthly headache days (MHD), migraine disability assessment (MIDAS), and average pain intensity (API) were extracted at baseline and every 6 months for up to 48 months using a predefined outcome form at each visit. Longitudinal changes were analyzed using generalized estimating equations (GEE) with an unstructured correlation matrix, adjusting for age, sex, and body mass index (BMI). Analyses were performed in four predefined analytic cohorts: all initiators, on-treatment, continuation, and discontinuation. Estimated marginal means (EMMs) quantified adjusted mean changes from baseline at each timepoint. No imputation or censoring for treatment discontinuation was applied. Treatment persistence, reasons for discontinuation, factors associated with discontinuation, and post-discontinuation anti-CGRP treatment patterns were summarized descriptively.ResultsAmong 112 patients (mean age 50.2 ± 13.7; 77.7% female; baseline MHD median 30 [IQR 25-30]), most had failed prior anti-CGRP therapies (90.2% ≥ 1 failure; 70.6% ≥ 2 failures). In all-initiators, significant reductions in MHD were observed at 6, 18-42, corresponding to model-estimated reductions of 1.5-1.9 MHD. MIDAS increased at 6 months, corresponding to a 44-point increase, but declined over time. API improved significantly at 24, 36 and 48 months, corresponding to a 0.4-0.6-point reduction. Treatment persistence declined to 55.4%, 39.2%, 35.7%, and 29.5% at 1, 2, 3, and 4 years, respectively; the median time to discontinuation was 8 months. Ineffectiveness (34.2%), loss of effectiveness (19.0%), and insurance-related barriers (16.5%) were the most common reasons for discontinuation. After discontinuation, 54.4% initiated another anti-CGRP therapy, 26.6% stopped anti-CGRP therapy entirely, and 20.3% were lost to follow-up.ConclusionsIn this treatment-resistant CM cohort, eptinezumab produced modest but durable benefit, particularly among patients who continued treatment. Persistence declined substantially over time, and post-discontinuation care followed diverse and often complex pathways. Regular reassessment and timely adjustment of preventive strategies remain essential as clinical responses evolve. Larger prospective studies will help clarify long-term effectiveness and treatment trajectories.

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This work is licensed under a Creative Commons Attribution-Noncommercial 4.0 License

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Supplementary Material.docx (40 kB)

PubMed ID

42153799

Language

English

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