{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T20:46:37Z","timestamp":1782938797650,"version":"3.54.5"},"reference-count":36,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T00:00:00Z","timestamp":1782345600000},"content-version":"vor","delay-in-days":24,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100000780","name":"European Commission","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000780","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Brain and Behavior"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Anti\u2010CGRP antibodies are effective and safe in real\u2010world migraine management, but guidelines recommend discontinuation after 12\u201318 months due to limited long\u2010term data and remaining uncertainties regarding optimal treatment duration and sustained safety, highlighting the need for large\u2010scale long\u2010term real\u2010world evidence. This study evaluated their safety and effectiveness in patients treated for \u22652 years.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This multicenter retrospective study included patients from 13 headache units who received the same anti\u2010CGRP antibody for \u226524 months, excluding discontinuation periods. Baseline characteristics, monthly headache days (MHD), monthly migraine days (MMD), and adverse events (AEs) were recorded at baseline, 6 months, 1, 2, 3, and 4 years. Descriptive statistics were used to summarize clinical characteristics, and appropriate parametric or non\u2010parametric tests were applied for group comparisons. Multivariate analyses were performed to explore associations between baseline variables and long\u2010term treatment response.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      A total of 454 patients (91% female, mean age 48) were analyzed, with follow\u2010up at 2 years (\n                      <jats:italic>n<\/jats:italic>\n                      = 454), 3 years (\n                      <jats:italic>n<\/jats:italic>\n                      = 135), and 4 years (\n                      <jats:italic>n<\/jats:italic>\n                      = 17). Treatments included erenumab (39%), galcanezumab (34%), and fremanezumab (27%). Fifty\u2010seven percent maintained continuous therapy, while 43% restarted after discontinuation. Sustained reductions in MHD and MMD were observed at 2, 3, and 4 years (MHD from 20 to 6, 6, 5\/MMD from 14 to 4, 4, and 2). Medication overuse decreased from 78% to 13%, 20%, and 18%. Loss of effectiveness occurred in 4.2% after 2 years. AEs appeared in &lt;20%, mostly mild (&gt;80%), leading to discontinuation in 0.4%. Multivariate analysis showed that shorter disease duration prior to anti\u2010CGRP initiation, earlier anti\u2010CGRP initiation, and greater MHD\/MMD reduction at 6 months were associated with better long\u2010term outcomes.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Anti\u2010CGRP mAbs demonstrate sustained long\u2010term safety and effectiveness, with consistent reduction in headache and migraine days and lower medication overuse. Early initiation and greater initial improvement predict better long\u2010term outcomes. Findings support extending therapy beyond 12\u201318 months, supporting optimization of clinical protocols.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/brb3.71560","type":"journal-article","created":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T15:38:31Z","timestamp":1782401911000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["ESTELA\u2010Study: Long\u2010Term Effectiveness and Safety of Anti\u2010Calcitonin Gene\u2010Related Peptide Monoclonal Antibodies in Real\u2010World Clinical Practice"],"prefix":"10.1002","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-6804-0832","authenticated-orcid":false,"given":"Alba","family":"Somovilla","sequence":"first","affiliation":[{"name":"Headache Unit, Department of Neurology, Health Research Institute La Princesa University Hospital  Madrid 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University Hospital  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nuria","family":"Gonz\u00e1lez\u2010Garc\u00eda","sequence":"additional","affiliation":[{"name":"Headache Unit, Department of Neurology, Health Research Institute Cl\u00ednico San Carlos Hospital  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda\u2010Luz","family":"Cuadrado","sequence":"additional","affiliation":[{"name":"Headache Unit, Department of Neurology, Health Research Institute Cl\u00ednico San Carlos Hospital  Madrid Spain"},{"name":"Department of Medicine School of Medicine Universidad Complutense de Madrid  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jes\u00fas","family":"Porta\u2010Etessam","sequence":"additional","affiliation":[{"name":"Headache Unit, Department of Neurology Fundaci\u00f3n Jim\u00e9nez D\u00edaz University Hospital  Madrid 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