{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,7]],"date-time":"2026-11-07T22:51:36Z","timestamp":1794091896692,"version":"4.8.0"},"reference-count":35,"publisher":"SAGE Publications","issue":"8","license":[{"start":{"date-parts":[[2025,6,19]],"date-time":"2025-06-19T00:00:00Z","timestamp":1750291200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Mult Scler"],"published-print":{"date-parts":[[2025,7]]},"abstract":"<jats:sec>\n                    <jats:title>Objectives:<\/jats:title>\n                    <jats:p>To assess the impact of age on the superiority of highly effective (HE) disease-modifying treatments (DMTs) compared to platform DMTs in a real-world population of relapsing MS patients (pwMS).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>A total of 20,984 pwMS were extracted from the Italian Multiple Sclerosis Register with a diagnosis of Clinically Isolated Syndrome or Relapsing-Remitting MS, at least four Expanded Disability Status Scale (EDSS) evaluations and 2 years follow-up, starting DMT. The baseline was the nearest visit to the first DMT starting date. The risk of first 24-week confirmed disability accumulation (CDA) on EDSS in HE versus platform DMTs after 2 years and the entire follow-up was assessed through Cox regression models.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      After 1:1 propensity score matching, we evaluated 1698 pwMS initiating HE-DMTs and 1698 initiating platforms. After 2 years follow-up, the proportion of CDA events was lower in patients on HE-DMTs (12.2%) than those on platform DMTs (15%), as confirmed by Cox regression analysis (hazard ratio (HR) = 0.22, 95% confidence interval (CI) = 0.10\u20130.47;\n                      <jats:italic>p<\/jats:italic>\n                      &lt; 0.001). HE-DMTs were more effective in patients under 45 years of age (HR = 0.49, 95% CI = 0.39\u20130.63;\n                      <jats:italic>p<\/jats:italic>\n                      &lt; 0.001), but not in patients over 45 (HR = 0.77, 95% CI = 0.54\u20131.08,\n                      <jats:italic>p<\/jats:italic>\n                      = 0.125). Notably, prolonged exposure to any DMT during follow-up reduced disability accumulation even in patients over 45 (HR = 0.13, 95% CI = 0.02\u20130.99;\n                      <jats:italic>p<\/jats:italic>\n                      = 0.050).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>This real-world study of relapsing pwMS demonstrates that the benefit of initial HE treatment diminishes with age. However, even in older patients, DMT exposure, regardless of the efficacy level, appears to reduce disability accumulation, and so, on an individual level, initial HE treatment could still be more effective.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/13524585251345317","type":"journal-article","created":{"date-parts":[[2025,6,19]],"date-time":"2025-06-19T04:27:09Z","timestamp":1750307229000},"page":"985-994","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":5,"title":["Age-dependent response to initial highly effective treatment in relapsing multiple sclerosis"],"prefix":"10.1177","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9662-1762","authenticated-orcid":false,"given":"Emilio","family":"Portaccio","sequence":"first","affiliation":[{"name":"Department of NEUROFARBA, Section of Neurology, University of Florence, Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6621-3971","authenticated-orcid":false,"given":"Matteo","family":"Betti","sequence":"additional","affiliation":[{"name":"Department of NEUROFARBA, Section of Neurology, University of Florence, Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5531-1111","authenticated-orcid":false,"given":"Ermelinda","family":"De Meo","sequence":"additional","affiliation":[{"name":"Department of NEUROFARBA, Section of Neurology, University of Florence, Florence, Italy"},{"name":"NMR Research Unit, Queen Square Multiple Sclerosis Centre, UCL Queen Square Institute of Neurology, University College London, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luisa","family":"Past\u00f2","sequence":"additional","affiliation":[{"name":"Department of NEUROFARBA, Section of Neurology, University of Florence, Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorenzo","family":"Razzolini","sequence":"additional","affiliation":[{"name":"Department of NEUROFARBA, Section of Neurology, University of Florence, Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6923-0846","authenticated-orcid":false,"given":"Francesco","family":"Patti","sequence":"additional","affiliation":[{"name":"Department of Medical, Surgical Sciences and Advanced Technologies \u201cG.F. Ingrassia,\u201d University of Catania, Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincenzo","family":"Brescia Morra","sequence":"additional","affiliation":[{"name":"Department of Neurosciences, Reproductive and Odontostomatological Sciences, Multiple Sclerosis Clinical Care and Research Center, University of Naples Federico II, Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanna","family":"De Luca","sequence":"additional","affiliation":[{"name":"Multiple Sclerosis Centre, Neurology Unit, University Hospital SS Annunziata, University G. d\u2019Annunzio Chieti-Pescara, Chieti, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlo","family":"Pozzilli","sequence":"additional","affiliation":[{"name":"Department of Human Neurosciences, Sapienza University of Rome, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9037-7300","authenticated-orcid":false,"given":"Carla","family":"Tortorella","sequence":"additional","affiliation":[{"name":"Department of Neurosciences, San Camillo Forlanini Hospital, Roma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3878-8820","authenticated-orcid":false,"given":"Eleonora","family":"Cocco","sequence":"additional","affiliation":[{"name":"Department of Medical Science and Public Health, Centro Sclerosi Multipla, University of Cagliari, Cagliari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Salemi","sequence":"additional","affiliation":[{"name":"Department of Biomedicine, Neuroscience and Advanced Diagnostics, University of Palermo, Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diana","family":"Ferraro","sequence":"additional","affiliation":[{"name":"Department of Neurosciences, Ospedale Civile di Baggiovara, Azienda Ospedaliero-Universitaria di Modena, Modena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marika","family":"Vianello","sequence":"additional","affiliation":[{"name":"Ca\u2019 Foncello Hospital, AULSS2, Neurology, Treviso, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giacomo","family":"Lus","sequence":"additional","affiliation":[{"name":"Department of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, Napoli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2902-5589","authenticated-orcid":false,"given":"Alessandra","family":"Lugaresi","sequence":"additional","affiliation":[{"name":"IRCCS Istituto delle Scienze Neurologiche di Bologna, Bologna, Italy"},{"name":"Dipartimento di Scienze Biomediche e Neuromotorie, Universit\u00e0 di Bologna, Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matilde","family":"Inglese","sequence":"additional","affiliation":[{"name":"Dipartimento di Neuroscienze, Riabilitazione, Oftalmologia, Genetica e Scienze Materno-Infantili (DINOGMI), Universit\u00e0 di Genova, Genova, Italy"},{"name":"IRCCS Ospedale Policlinico San Martino, Genova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gioacchino","family":"Tedeschi","sequence":"additional","affiliation":[{"name":"I Division of Neurology, Universita della Campania \u201cL. Vanvitelli,\u201d Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Montepietra","sequence":"additional","affiliation":[{"name":"MS Centre, SMN Hospital, AUSL Reggio Emilia, Reggio Emilia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessia","family":"Di Sapio","sequence":"additional","affiliation":[{"name":"Department of Neurology, Regional Referral Multiple Sclerosis Center, University Hospital San Luigi Gonzaga, Orbassano, Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mauro","family":"Zaffaroni","sequence":"additional","affiliation":[{"name":"Multiple Sclerosis Center, Hospital of Gallarate\u2014ASST Della Valle Olona, Gallarate, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2308-1731","authenticated-orcid":false,"given":"Pietro","family":"Iaffaldano","sequence":"additional","affiliation":[{"name":"Department of Basic Medical Sciences, Neurosciences and Sense Organs, University of Bari Aldo Moro, Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4381-4613","authenticated-orcid":false,"given":"Marta","family":"Simone","sequence":"additional","affiliation":[{"name":"Child Neuropsychiatry Unit, Department of Precision and Regenerative Medicine and Jonic Area, University of Bari Aldo Moro, Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5485-0479","authenticated-orcid":false,"given":"Massimo","family":"Filippi","sequence":"additional","affiliation":[{"name":"Vita-Salute San Raffaele University, Milano, Italy"},{"name":"Neuroimaging Research Unit, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milano, Italy"},{"name":"Neurology Unit and Multiple Sclerosis Center, Neurorehabilitation Unit, and Neurophysiology Service, IRCCS San Raffaele Scientific Institute, Milano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6329-8946","authenticated-orcid":false,"given":"Maria","family":"Trojano","sequence":"additional","affiliation":[{"name":"Department of Basic Medical Sciences, Neurosciences and Sense Organs, University of Bari Aldo Moro, Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3325-3760","authenticated-orcid":false,"given":"Maria Pia","family":"Amato","sequence":"additional","affiliation":[{"name":"Department of NEUROFARBA, Section of Neurology, University of Florence, Florence, Italy"},{"name":"IRCCS Don Carlo Gnocchi Foundation, Florence, 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