{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T23:34:48Z","timestamp":1793230488158,"version":"4.5.0"},"reference-count":24,"publisher":"Springer Science and Business Media LLC","issue":"5","license":[{"start":{"date-parts":[[2024,1,17]],"date-time":"2024-01-17T00:00:00Z","timestamp":1705449600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,1,17]],"date-time":"2024-01-17T00:00:00Z","timestamp":1705449600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"This work was partially supported by the Italian Ministry of Health (Institutional Funding Ricerca Corrente) IRCCS San Raffaele Roma and by Fondazione Italiana Cefalee (FICEF).","id":[{"id":"https:\/\/ror.org\/006x48140","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Neurol"],"published-print":{"date-parts":[[2024,5]]},"abstract":"Abstract<\/jats:title>\n \n Objective<\/jats:title>\n \n Nearly 60% of migraine patients treated with monoclonal antibodies (mAbs) targeting the calcitonin gene-related peptide (CGRP) pathway experience a\u2009\u2265\u200950% reduction in monthly migraine days (MMD) at 12\u00a0weeks compared to baseline\n (responders)<\/jats:italic>\n . However, approximately half of the patients not responding to anti-CGRP mAbs\u2009\u2264\u200912\u00a0weeks do respond\u2009\u2264\u200924\u00a0weeks (\n late responders)<\/jats:italic>\n . We assessed frequency and characteristics of patients responding to anti-CGRP mAbs only\u2009>\u200924\u00a0weeks (\n ultra-late responders<\/jats:italic>\n ).\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n In this multicenter (\n n<\/jats:italic>\n \u2009=\u200916), prospective, observational, real-life study, we enrolled all consecutive adults affected by high-frequency episodic migraine (HFEM:\u2009\u2265\u20098\u00a0days\/month) or chronic migraine (CM), with\u2009\u2265\u20093 prior therapeutic failures, treated with any anti-CGRP mAbs for\u2009\u2265\u200948\u00a0weeks. We defined\n responders<\/jats:italic>\n patients with a\u2009\u2265\u200950% response rate\u2009\u2264\u200912\u00a0weeks,\n late responders<\/jats:italic>\n those with a\u2009\u2265\u200950% response rate\u2009\u2264\u200924\u00a0weeks, and\n ultra-late responders<\/jats:italic>\n those achieving a\u2009\u2265\u200950% response only\u2009>\u200924\u00a0weeks.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n A total of 572 migraine patients completed\u2009\u2265\u200948\u00a0weeks of anti-CGRP mAbs treatment.\n Responders<\/jats:italic>\n accounted for 60.5% (346\/572),\n late responders<\/jats:italic>\n for 15% (86\/572), and\n ultra-late responders<\/jats:italic>\n for 15.7% (90\/572). Among\n ultra-late responders<\/jats:italic>\n , 7.3% (42\/572) maintained the\u2009\u2265\u200950% response rate across all subsequent time intervals (weeks 28, 32, 36, 40, 44, and 48) and were considered\n persistent ultra-late responders<\/jats:italic>\n , while 8.4% (48\/572) missed the\u2009\u2265\u200950% response rate at\u2009\u2265\u20091 subsequent time interval and were classified as\n fluctuating ultra-late responders<\/jats:italic>\n . Fifty patients (8.7%) did not respond at any time interval\u2009\u2264\u200948\u00a0weeks.\n Ultra-late responders<\/jats:italic>\n differed from\n responders<\/jats:italic>\n for higher BMI (\n p<\/jats:italic>\n \u2009=\u20090.033), longer duration of medication overuse (\n p<\/jats:italic>\n \u2009<\u20090.001), lower NRS (\n p<\/jats:italic>\n \u2009=\u20090.017) and HIT-6 scores (\n p<\/jats:italic>\n \u2009=\u20090.002), higher frequency of dopaminergic symptoms (\n p<\/jats:italic>\n \u2009=\u20090.002), less common unilateral pain\u2014either alone (\n p<\/jats:italic>\n \u2009=\u20090.010) or in combination with UAS (\n p<\/jats:italic>\n \u2009=\u20090.023), allodynia (\n p<\/jats:italic>\n \u2009=\u20090.043), or UAS and allodynia (\n p<\/jats:italic>\n \u2009=\u20090.012)\u2014a higher number of comorbidities (\n p<\/jats:italic>\n \u2009=\u20090.012), psychiatric comorbidities (\n p<\/jats:italic>\n \u2009=\u20090.010) and a higher proportion of patients with\u2009\u2265\u20091 comorbidity (\n p<\/jats:italic>\n \u2009=\u20090.020).\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n \n Two-thirds of patients not responding to anti-CGRP mAbs\u2009\u2264\u200924\u00a0weeks do respond later, while\n non-responders<\/jats:italic>\n \u2009\u2264\u200948\u00a0weeks are quite rare (8.7%). These findings suggest to rethink the duration of migraine prophylaxis and the definition of resistant and refractory migraine, currently based on the response after 2\u20133\u00a0months of treatment.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1007\/s00415-023-12103-4","type":"journal-article","created":{"date-parts":[[2024,1,17]],"date-time":"2024-01-17T09:02:48Z","timestamp":1705482168000},"page":"2434-2443","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":45,"title":["Ultra-late response (>\u200924\u00a0weeks) to anti-CGRP monoclonal antibodies in migraine: a multicenter, prospective, observational study"],"prefix":"10.1007","volume":"271","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5670-3755","authenticated-orcid":false,"given":"Piero","family":"Barbanti","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cinzia","family":"Aurilia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriella","family":"Egeo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefania","family":"Proietti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florindo","family":"D\u2019Onofrio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"Torelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Aguggia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Davide","family":"Bertuzzo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cinzia","family":"Finocchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michele","family":"Trimboli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabina","family":"Cevoli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia","family":"Fiorentini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bianca","family":"Orlando","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maurizio","family":"Zucco","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Di Clemente","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilaria","family":"Cetta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruno","family":"Colombo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monica Laura Bandettini","family":"di Poggio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentina","family":"Favoni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Licia","family":"Grazzi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Salerno","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Carnevale","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Micaela","family":"Robotti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabio","family":"Frediani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Altamura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Massimo","family":"Filippi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabrizio","family":"Vernieri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefano","family":"Bonassi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"ERT; for the Italian Migraine Registry study group","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,1,17]]},"reference":[{"issue":"1","key":"12103_CR1","doi-asserted-by":"publisher","first-page":"117","DOI":"10.1186\/s10194-019-1066-0","volume":"20","author":"AP Andreou","year":"2019","unstructured":"Andreou AP, Edvinsson L (2019) Mechanisms of migraine as a chronic evolutive condition. 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Cinzia Aurilia received travel grants from Eli-Lilly, FB-Health, Lusofarmaco and Teva, honoraria from Novartis, Eli-Lilly and Teva; Gabriella Egeo received travel grants and honoraria from Eli-Lilly, Novartis, New Penta and Ecupharma; Florindo d\u2019Onofrio received travel grant, honoraria as a speaker or for participating in advisory boards from Novartis, Teva, Neopharmed Gentili, Qbgroup srl, K link srl and Eli-Lilly; Paola Torelli received travel grant, honoraria as a speaker, or for participating in advisory boards from Novartis, Teva, Eli Lilly, and Allergan; Cinzia Finocchi received grants and honoraria from Novartis, Eli Lilly, TEVA, AIM group; Sabina Cevoli received honoraria for speaker panels from Teva and Novartis; Maurizio Zucco received travel grants and honoraria from Novartis; Bruno Colombo received travel grants, honoraria for advisory boards, speaker panels or investigation studies from Novartis, Teva, Lilly e Lusofarmaco; Valentina Favoni received honoraria as speaker or for participating in advisory boards from Ely-Lilly, Novartis and Teva; Licia Grazzi received consultancy and advisory fees or honoraria for investigation studies from Allergan, Electrocore LLC, Novartis, Ely-Lilly and Teva; Frediani Fabio received honoraria as speaker or for participating in advisory boards from Novartis, Teva and Eli-Lilly; Claudia Altamura received honoraria for speaker panels from Novartis and Teva; Massimo Filippi is Editor-in-Chief of the Journal of Neurology; received compensation for consulting services and\/or speaking activities from Bayer, Biogen Idec, Merck-Serono, Novartis, Roche, Sanofi Genzyme, Takeda, and Teva; and receives research support from Biogen Idec, Merck-Serono, Novartis, Roche, Teva, Italian Ministry of Health, Fondazione Italiana Sclerosi Multipla, and ARiSLA (Fondazione Italiana di Ricerca per la SLA); Fabrizio Vernieri received travel grants, honoraria for advisory boards, speaker panels, or clinical investigation studies from Allergan, Eli-Lilly, Novartis, and Teva; Stefania Proietti, Marco Aguggia, Davide Bertuzzo, Michele Trimboli, Ilaria Cetta, Monica Laura Bandettini di Poggio, Giulia Fiorentini, Bianca Orlando, Laura Di Clemente, Antonio Salerno, Antonio Carnevale, Micaela Robotti and Stefano Bonassi have no disclosures to declare.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflicts of interest"}}]}}