{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T19:22:05Z","timestamp":1792264925613,"version":"4.4.0"},"reference-count":27,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2025,7,6]],"date-time":"2025-07-06T00:00:00Z","timestamp":1751760000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Ann Clin Transl Neurol"],"published-print":{"date-parts":[[2025,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To evaluate the long\u2010term impact of early intensive treatment (EIT) versus escalation (ESC) strategies using high\u2010efficacy disease\u2010modifying therapies (HE\u2010DMTs) on disability progression in relapsing multiple sclerosis (RMS).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This observational study included 4878 RMS patients from the Italian Multiple Sclerosis Register. Eligible participants initiated their first disease\u2010modifying therapy (DMT) within 3\u2009years of disease onset and had \u2265\u20095\u2009years of follow\u2010up with at least three Expanded Disability Status Scale (EDSS) evaluations. Patients were categorized into the EIT group if they started with HE\u2010DMTs and into the ESC group if HE\u2010DMTs were initiated after \u2265\u20091\u2009year of moderate\u2010efficacy therapy. Propensity score matching was performed to balance baseline characteristics. Outcomes included disability trajectories assessed using linear mixed models for repeated measures and risks of confirmed disability accrual (CDA), progression independent of relapse activity (PIRA), and relapse\u2010associated worsening (RAW) evaluated using Cox proportional hazards models.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Post\u2010matching analysis of 908 pairs revealed significantly slower disability progression in the EIT group compared to the ESC group. At 10\u2009years, the delta\u2010EDSS difference between groups was \u22120.63 (95% CI: \u22120.83 to \u22120.43;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.0001). ESC was associated with higher risks of CDA (HR 1.36, 95% CI: 1.20\u20131.54;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.0001), PIRA (HR 1.22, 95% CI: 1.05\u20131.40;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.0074), and RAW (HR 1.55, 95% CI: 1.17\u20132.05;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.0021).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Interpretation<\/jats:title>\n                    <jats:p>EIT significantly reduces long\u2010term disability progression in RMS compared to ESC. These findings underscore the potential of EIT to optimize long\u2010term outcomes in RMS patients.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/acn3.70131","type":"journal-article","created":{"date-parts":[[2025,7,7]],"date-time":"2025-07-07T01:23:32Z","timestamp":1751851412000},"page":"2012-2019","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Early Intensive Versus Escalation Approach: Ten\u2010Year Impact on Disability in Relapsing Multiple Sclerosis"],"prefix":"10.1002","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2308-1731","authenticated-orcid":false,"given":"Pietro","family":"Iaffaldano","sequence":"first","affiliation":[{"name":"Department of Translational Biomedicines and Neurosciences (DiBraiN) University of Bari \u201cAldo Moro\u201d  Bari Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Lucisano","sequence":"additional","affiliation":[{"name":"CORESEARCH\u2014Center for Outcomes Research and Clinical Epidemiology  Pescara Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tommaso","family":"Guerra","sequence":"additional","affiliation":[{"name":"Department of Translational Biomedicines and Neurosciences (DiBraiN) University of Bari \u201cAldo Moro\u201d  Bari Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Caputo","sequence":"additional","affiliation":[{"name":"Department of Translational Biomedicines and Neurosciences (DiBraiN) University of Bari \u201cAldo Moro\u201d  Bari Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Simone","sequence":"additional","affiliation":[{"name":"Child Neuropsychiatry Unit, Department of Precision and Regenerative Medicine Jonic Area University of Bari \u201cAldo Moro\u201d  Bari Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Massimiliano","family":"Copetti","sequence":"additional","affiliation":[{"name":"Fondazione IRCCS\u2014\u201cCasa Sollievo Della Sofferenza,\u201d Unit of Biostatistics  San Giovanni Rotondo Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Damiano","family":"Paolicelli","sequence":"additional","affiliation":[{"name":"Department of Translational Biomedicines and Neurosciences (DiBraiN) University of Bari \u201cAldo Moro\u201d  Bari Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emilio","family":"Portaccio","sequence":"additional","affiliation":[{"name":"Department of NEUROFARBA University of Florence  Florence Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Patti","sequence":"additional","affiliation":[{"name":"Department \u201cGF Ingrassia,\u201d Section of Neurosciences, Neurology Clinic University of Catania  Catania Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"Perini","sequence":"additional","affiliation":[{"name":"Department of Neurosciences, Multiple Sclerosis Centre\u2010Veneto Region (CeSMuV) University Hospital of Padua  padua Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincenzo","family":"Brescia Morra","sequence":"additional","affiliation":[{"name":"Department of Neuroscience (NSRO) Multiple Sclerosis Clinical Care and Research Center, Federico II University  Naples Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessia","family":"Di Sapio","sequence":"additional","affiliation":[{"name":"Regional Referral MS Center, Neurological Unit Univ. Hospital San Luigi Gonzaga  Orbassano Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matilde","family":"Inglese","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DINOGMI) University of Genoa  Genoa Italy"},{"name":"IRCCS Ospedale Policlinico San Martino  Genoa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlo","family":"Pozzilli","sequence":"additional","affiliation":[{"name":"Department of Human Neuroscience Sapienza University  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giacomo","family":"Lus","sequence":"additional","affiliation":[{"name":"Multiple Sclerosis Center, II Division of Neurology, Department of Clinical and Experimental Medicine Second University of Naples  Naples 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":"Erica","family":"Curti","sequence":"additional","affiliation":[{"name":"Unit of Neurosciences, Department of Medicine and Surgery University of Parma  Parma Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanna","family":"De Luca","sequence":"additional","affiliation":[{"name":"Multiple Sclerosis Centre, Neurology Unit University Hospital SS Annunziata, Chieti, University G. d'Annunzio  Chieti\u2010Pescara Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"Valentino","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences Institute of Neurology, Magna Graecia University  Catanzaro Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eleonora","family":"Cocco","sequence":"additional","affiliation":[{"name":"Department of Medical Science and Public Health, Multiple Sclerosis Center University of Cagliari  Cagliari Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"Cavalla","sequence":"additional","affiliation":[{"name":"Multiple Sclerosis Center and 1 Division of Neurology, Department of Neuroscience University of Turin &amp; City of Health and Science University Hospital  Turin Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlo","family":"Avolio","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences University of Foggia  Foggia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandra","family":"Lugaresi","sequence":"additional","affiliation":[{"name":"UOSI Riabilitazione Sclerosi Multipla 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":"Antonio","family":"Gallo","sequence":"additional","affiliation":[{"name":"Department of Advanced Medical and Surgical Sciences University of Campania \u201cLuigi Vanvitelli\u201d  Naples Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pietro","family":"Annovazzi","sequence":"additional","affiliation":[{"name":"Neuroimmunology Unit, Multiple Sclerosis Center Hospital of Gallarate, ASST Della Valle Olona  Gallarate (Varese) Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2358-4320","authenticated-orcid":false,"given":"Maria A.","family":"Rocca","sequence":"additional","affiliation":[{"name":"Neuroimaging Research Unit, Division of Neuroscience IRCCS Ospedale San Raffaele  Milano Italy"},{"name":"Neurology 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