{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T14:48:51Z","timestamp":1791902931511,"version":"4.3.4"},"reference-count":15,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T00:00:00Z","timestamp":1791849600000},"content-version":"vor","delay-in-days":12,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Euro J of Neurology"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Highly effective (HE) disease\u2010modifying therapies (DMTs) reduce relapse\u2010associated worsening (RAW) and progression independent of relapse activity (PIRA). Natalizumab (NTZ) and anti\u2010CD20 agents show similar efficacy on relapse suppression, but long\u2010term comparative data on PIRA are limited. We aimed to compare PIRA accrual in relapsing\u2013remitting MS (RRMS) patients treated with NTZ and anti\u2010CD20 drugs over a long follow\u2010up.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We included RRMS patients followed at our centre and recorded in the Italian MS and Related Disorders Register with at least 5\u2009years of continuous treatment with NTZ or anti\u2010CD20 agents (Ocrelizumab, Rituximab, Ofatumumab), at least 3 Expanded Disability Status Scale (EDSS) assessments, and complete demographic and clinical data. Patients were matched for gender, age, EDSS, disease duration, MS phenotype at treatment initiation. Logistic regression and Cox proportional hazard models were applied.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Of 267 eligible patients (178 NTZ, 89 anti\u2010CD20), optimal matching yielded 89 balanced pairs. A first PIRA event was observed in 27.0% of NTZ\u2010treated and 28.1% of anti\u2010CD20\u2010treated patients. The total number of PIRA events was comparable between NTZ\u2010treated and anti\u2010CD20\u2010treated patients (36 vs. 30;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.451). Adjusted analyses revealed no significant differences in cumulative risk (RR: 1.48; 95% CI: 0.66\u20133.40;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.333) or time to first PIRA event (HR: 1.51; 95% CI 0.83\u20132.77;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.179).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>In this real\u2010world cohort with long\u2010term follow\u2010up, NTZ and anti\u2010CD20 therapies showed no significant differences in PIRA accrual or time to first PIRA, suggesting comparable long\u2010term control of disability progression beyond relapse. Larger studies are warranted to confirm and refine these observations.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/ene.70771","type":"journal-article","created":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T14:23:02Z","timestamp":1791901382000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Anti\u2010\n                    <scp>CD20<\/scp>\n                    Drugs and Natalizumab Confer Equal Protection Against Progression Independent of Relapse Activity (\n                    <scp>PIRA<\/scp>\n                    ) in People With Multiple Sclerosis"],"prefix":"10.1111","volume":"33","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2652-7447","authenticated-orcid":false,"given":"Leonardo","family":"Palazzo","sequence":"first","affiliation":[{"name":"Neurology Unit and MS Center IRCCS Ospedale San Raffaele  Milan Lombardy Italy"},{"name":"Universit\u00e0 Vita\u2010Salute San Raffaele  Milan Lombardy Italy"},{"name":"Laboratory of Human Genetics of Neurological Disorders, Division of Neuroscience IRCCS San Raffaele Scientific Institute  Milan Lombardy Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9561-4360","authenticated-orcid":false,"given":"Ferdinando","family":"Clarelli","sequence":"additional","affiliation":[{"name":"Laboratory of Human Genetics of Neurological Disorders, Division of Neuroscience IRCCS San Raffaele Scientific Institute  Milan Lombardy Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michele","family":"Surano","sequence":"additional","affiliation":[{"name":"Neurology Unit and MS Center IRCCS Ospedale San Raffaele  Milan Lombardy Italy"},{"name":"Universit\u00e0 Vita\u2010Salute San Raffaele  Milan Lombardy Italy"},{"name":"Laboratory of Human Genetics of Neurological Disorders, Division of Neuroscience IRCCS San Raffaele Scientific Institute  Milan Lombardy Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3685-8311","authenticated-orcid":false,"given":"Antonino","family":"Giordano","sequence":"additional","affiliation":[{"name":"Neurology Unit and MS Center IRCCS Ospedale San Raffaele  Milan Lombardy Italy"},{"name":"Universit\u00e0 Vita\u2010Salute San Raffaele  Milan Lombardy Italy"},{"name":"Laboratory of Human Genetics of Neurological Disorders, Division of Neuroscience IRCCS San Raffaele Scientific Institute  Milan Lombardy Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6313-4952","authenticated-orcid":false,"given":"Lucia","family":"Moiola","sequence":"additional","affiliation":[{"name":"Neurology Unit and MS Center IRCCS Ospedale San Raffaele  Milan Lombardy Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"Clinical SanRaf MS Study Group","sequence":"additional","affiliation":[],"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":"Neurology Unit and MS Center IRCCS Ospedale San Raffaele  Milan Lombardy Italy"},{"name":"Universit\u00e0 Vita\u2010Salute San Raffaele  Milan Lombardy 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":"Neurology Unit and MS Center IRCCS Ospedale San Raffaele  Milan Lombardy Italy"},{"name":"Universit\u00e0 Vita\u2010Salute San Raffaele  Milan Lombardy Italy"},{"name":"Laboratory of Human Genetics of Neurological Disorders, Division of Neuroscience IRCCS San Raffaele Scientific Institute  Milan Lombardy Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2550-0805","authenticated-orcid":false,"given":"Federica","family":"Esposito","sequence":"additional","affiliation":[{"name":"Neurology Unit and MS Center IRCCS Ospedale San Raffaele  Milan Lombardy Italy"},{"name":"Laboratory of Human Genetics of Neurological Disorders, Division of Neuroscience IRCCS San Raffaele Scientific Institute  Milan Lombardy Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,13]]},"reference":[{"issue":"9","key":"e_1_2_10_2_1","doi-asserted-by":"crossref","first-page":"3147","DOI":"10.1093\/brain\/awac016","article-title":"How Patients With Multiple Sclerosis Acquire Disability","volume":"145","author":"Lublin F. 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Multiple Sclerosis: An Observational Study in the Swiss Multiple Sclerosis Cohort","volume":"272","author":"Cagol A.","year":"2025","journal-title":"Journal of Neurology"},{"issue":"5","key":"e_1_2_10_6_1","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1136\/jnnp-2024-335704","article-title":"Comparative Effectiveness of Natalizumab and Anti\u2010CD20 Monoclonal Antibodies in Relapsing\u2010Remitting Multiple Sclerosis: A Real\u2010World Propensity\u2010Score Matched Study","volume":"97","author":"Yamout B.","year":"2026","journal-title":"Journal of Neurology, Neurosurgery, and Psychiatry"},{"key":"e_1_2_10_7_1","doi-asserted-by":"crossref","DOI":"10.1177\/17562864221142924","article-title":"Comparative Effectiveness of Natalizumab Versus Ocrelizumab in Multiple Sclerosis: A Real\u2010World Propensity Score\u2010Matched Study","volume":"15","author":"Pape K.","year":"2022","journal-title":"Therapeutic Advances in Neurological 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C.","year":"2026","journal-title":"European Journal of Neurology"},{"issue":"6","key":"e_1_2_10_11_1","doi-asserted-by":"crossref","first-page":"614","DOI":"10.1001\/jamaneurol.2025.0495","article-title":"Standardized Definition of Progression Independent of Relapse Activity (PIRA) in Relapsing\u2010Remitting Multiple Sclerosis","volume":"82","author":"M\u00fcller J.","year":"2025","journal-title":"JAMA Neurology"},{"issue":"9","key":"e_1_2_10_12_1","doi-asserted-by":"crossref","first-page":"1185","DOI":"10.1177\/13524585241243157","article-title":"Creating an Automated Tool for a Consistent and Repeatable Evaluation of Disability Progression in Clinical Studies for Multiple Sclerosis","volume":"30","author":"Montobbio N.","year":"2024","journal-title":"Multiple Sclerosis"},{"issue":"8","key":"e_1_2_10_13_1","first-page":"1","article-title":"MatchIt: Nonparametric Preprocessing for Parametric Causal Inference","volume":"42","author":"Ho D.","year":"2011","journal-title":"Journal of 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