{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:34:17Z","timestamp":1792787657692,"version":"4.5.0"},"reference-count":28,"publisher":"SAGE Publications","issue":"5","license":[{"start":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T00:00:00Z","timestamp":1777593600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T00:00:00Z","timestamp":1777593600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"name":"Patient philanthropy"},{"name":"Miles for migraine"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Cephalalgia"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>To 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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We 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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Among 112 patients (mean age 50.2\u2009\u00b1\u200913.7; 77.7% female; baseline MHD median 30 [IQR 25\u201330]), most had failed prior anti-CGRP therapies (90.2%\u2009\u2265\u20091 failure; 70.6%\u2009\u2265\u20092 failures). In all-initiators, significant reductions in MHD were observed at 6, 18\u201342, corresponding to model-estimated reductions of 1.5\u20131.9 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\u20130.6-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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>In 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.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/03331024261451427","type":"journal-article","created":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T13:38:16Z","timestamp":1779197896000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":2,"title":["Eptinezumab in treatment-resistant chronic migraine: Four-year real-world effectiveness and treatment persistence"],"prefix":"10.1177","volume":"46","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5004-9599","authenticated-orcid":false,"given":"Wan-Jen","family":"Hsieh","sequence":"first","affiliation":[{"name":"Thomas Jefferson University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelly","family":"Nicol","sequence":"additional","affiliation":[{"name":"Thomas Jefferson University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-0296-9311","authenticated-orcid":false,"given":"Chai Ching","family":"Ng","sequence":"additional","affiliation":[{"name":"Thomas Jefferson University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tsung-Wei","family":"Hou","sequence":"additional","affiliation":[{"name":"Thomas Jefferson University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Phillip","family":"Phan","sequence":"additional","affiliation":[{"name":"Thomas Jefferson University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott W.","family":"Keith","sequence":"additional","affiliation":[{"name":"Thomas Jefferson University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brittany","family":"Heckel","sequence":"additional","affiliation":[{"name":"Thomas Jefferson University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6421-6594","authenticated-orcid":false,"given":"Michael J.","family":"Marmura","sequence":"additional","affiliation":[{"name":"Thomas Jefferson University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4536-9974","authenticated-orcid":false,"given":"Hsiangkuo","family":"Yuan","sequence":"additional","affiliation":[{"name":"Thomas Jefferson University"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2026,5,19]]},"reference":[{"key":"e_1_3_3_2_2","article-title":"Efficacy and safety of eptinezumab in patients with chronic migraine: PROMISE-2","volume":"94","author":"Lipton RB","unstructured":"Lipton RB, Goadsby PJ, Smith J, et al. Efficacy and safety of eptinezumab in patients with chronic migraine: PROMISE-2. Neurology 2020 Mar 31; 94: e1365\u2013e1377.","journal-title":"Neurology"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1186\/s10194-023-01688-w"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12883-021-02123-w"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1186\/s10194-024-01788-1"},{"key":"e_1_3_3_6_2","first-page":"333102424128887","article-title":"Efficacy of eptinezumab in non-responders to subcutaneous monoclonal antibodies against CGRP and the CGRP receptor: a retrospective cohort study","volume":"44","author":"Triller P","unstructured":"Triller P, Blessing VN, Overeem LH, et al. Efficacy of eptinezumab in non-responders to subcutaneous monoclonal antibodies against CGRP and the CGRP receptor: a retrospective cohort study. Cephalalgia 2024 Oct; 44: 3331024241288875.","journal-title":"Cephalalgia"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1186\/s10194-025-02180-3"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-025-13095-z"},{"key":"e_1_3_3_9_2","article-title":"Patient adherence and long-term tolerability of anti-calcitonin gene-related peptide (CGRP) monoclonal antibodies in migraine prevention: a systematic review","volume":"17","author":"Ray R","unstructured":"Ray R, Virk GS, Regmi N, et al. Patient adherence and long-term tolerability of anti-calcitonin gene-related peptide (CGRP) monoclonal antibodies in migraine prevention: a systematic review. Cureus 2025 Aug 31; 17: e91347.","journal-title":"Cureus"},{"key":"e_1_3_3_10_2","first-page":"333102425135342","article-title":"Real world effectiveness of anti-CGRP monoclonal antibodies over three consecutive one-year treatment cycles: an intention-to-treat analysis","volume":"45","author":"Vaghi G","unstructured":"Vaghi G, Corrado M, Pocora MM, et al. Real world effectiveness of anti-CGRP monoclonal antibodies over three consecutive one-year treatment cycles: an intention-to-treat analysis. Cephalalgia 2025 Aug; 45: 3331024251353421.","journal-title":"Cephalalgia"},{"key":"e_1_3_3_11_2","first-page":"333102425131801","article-title":"Guidelines of the International Headache Society for Real-World Evidence studies in migraine and cluster headache","volume":"45","author":"Pozo-Rosich P","unstructured":"Pozo-Rosich P, van Veelen N, Caronna E, et al. Guidelines of the International Headache Society for Real-World Evidence studies in migraine and cluster headache. Cephalalgia 2025 Mar; 45: 3331024251318016.","journal-title":"Cephalalgia"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1186\/s10194-023-01611-3"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1186\/s10194-023-01636-8"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.18433\/jpps33158"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1111\/head.14827"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1177\/25158163251388920"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbi.2019.103208"},{"key":"e_1_3_3_18_2","first-page":"927","article-title":"Redefining migraine prevention: early treatment with anti-CGRP monoclonal antibodies enhances response in the real world","volume":"95","author":"Caronna E","unstructured":"Caronna E, Gallardo VJ, Egeo G, et al. Redefining migraine prevention: early treatment with anti-CGRP monoclonal antibodies enhances response in the real world. J Neurol Neurosurg Psychiatry 2024 Sep 17; 95: 927\u2013937.","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1186\/s10194-023-01556-7"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1526-4610.2003.03050.x"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1186\/s10194-021-01339-y"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1186\/s10194-021-01323-6"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.2147\/PPA.S346660"},{"key":"e_1_3_3_24_2","first-page":"1119","article-title":"Real-world persistence and costs among patients with chronic migraine treated with onabotulinumtoxinA or calcitonin gene-related peptide monoclonal antibodies","volume":"29","author":"Schwedt TJ","unstructured":"Schwedt TJ, Lee J, Knievel K, et al. Real-world persistence and costs among patients with chronic migraine treated with onabotulinumtoxinA or calcitonin gene-related peptide monoclonal antibodies. J Manag Care Spec Pharm 2023 Oct; 29: 1119\u20131128.","journal-title":"J Manag Care Spec Pharm"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11916-023-01183-6"},{"key":"e_1_3_3_26_2","article-title":"Long-Term effectiveness and persistence factors of anti-CGRP monoclonal antibodies in migraine: 2-year results from the EUREkA cohort","volume":"106","author":"Caronna E","unstructured":"Caronna E, Mas-de-Les-Valls R, Egeo G, et al. Long-Term effectiveness and persistence factors of anti-CGRP monoclonal antibodies in migraine: 2-year results from the EUREkA cohort. Neurology 2026 Feb 24; 106: e214659.","journal-title":"Neurology"},{"key":"e_1_3_3_27_2","first-page":"333102423116051","article-title":"Switching anti-CGRP(R) monoclonal antibodies in multi-assessed non-responder patients and implications for ineffectiveness criteria: a retrospective cohort study","volume":"43","author":"Iannone LF","unstructured":"Iannone LF, Burgalassi A, Vigani G, et al. Switching anti-CGRP(R) monoclonal antibodies in multi-assessed non-responder patients and implications for ineffectiveness criteria: a retrospective cohort study. 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