{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T03:10:41Z","timestamp":1792811441445,"version":"4.5.0"},"reference-count":35,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2025,1,1]],"date-time":"2025-01-01T00:00:00Z","timestamp":1735689600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2025,1,1]],"date-time":"2025-01-01T00:00:00Z","timestamp":1735689600000},"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":["Ther Adv Neurol Disord"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:sec>\n            <jats:title>Background:<\/jats:title>\n            <jats:p>Sex differences in multiple sclerosis (MS) progression are poorly characterized, especially for disability worsening independent of relapses.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Objectives:<\/jats:title>\n            <jats:p>To assess sex-specific risks of progression independent of relapse activity (PIRA), relapse and magnetic resonance imaging (MRI) activity (PIRMA), and relapse-associated worsening (RAW) in a real-world MS cohort, quantify each event\u2019s contribution to disability accumulation, and explore variation across clinical subgroups.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Design:<\/jats:title>\n            <jats:p>Inverse probability-weighted analysis of adults with relapsing-remitting MS ambispectively enrolled in a local registry who had their first recorded neurological evaluation within 12\u2009months of MS onset.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods:<\/jats:title>\n            <jats:p>We used weighted conditional proportional hazard models for recurrent events, adjusted for visit\/MRI frequency, to compare risks between sexes. We also tested the homogeneity of sex effects across prespecified subgroups: age at MS onset, symptom location at onset, presence of \u2a7e10 T2-hyperintense brain lesions, \u2a7e1 spinal T2 lesion, \u2a7e1 Gadolinium-enhancing brain lesion at baseline, initial MS treatment type, and percentage of follow-up time on disease-modifying therapy (DMT).<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results:<\/jats:title>\n            <jats:p>\n              We included 492 people with MS (median age 44.0\u2009years, interquartile range (IQR) 35.0\u201353.6; 68.9% women), followed for a median of 5.1\u2009years (IQR 3.1\u20137.2). In the weighted cohort, women had higher hazards of PIRA (hazard ratio (HR) 2.44, 95% confidence interval (CI) 1.56\u20133.70;\n              <jats:italic>p<\/jats:italic>\n              \u2009&lt;\u20090.001) and PIRMA (HR 2.13, 95% CI 1.25\u20133.70;\n              <jats:italic>p<\/jats:italic>\n              \u2009&lt;\u20090.001), mainly postmenopausal (56.6% and 52.4%). RAW risk was similar (HR 1.07, 95% CI 0.54\u20132.11;\n              <jats:italic>p<\/jats:italic>\n              \u2009=\u20090.843), despite higher relapse rates in women (0.13\u2009\u00b1\u20090.18 vs 0.06\u2009\u00b1\u20090.16;\n              <jats:italic>p<\/jats:italic>\n              \u2009&lt;\u20090.001). Men had greater Expanded Disability Status Scale worsening per PIRA (+0.29\u2009\u00b1\u20090.71 vs +0.16\u2009\u00b1\u20090.53;\n              <jats:italic>p<\/jats:italic>\n              \u2009=\u20090.023) and PIRMA (+0.25\u2009\u00b1\u20090.71 vs +0.09\u2009\u00b1\u20090.38;\n              <jats:italic>p<\/jats:italic>\n              \u2009=\u20090.001). Age \u2a7e50 at onset increased PIRA\/PIRMA risk without sex interaction. Significant sex interaction was seen for onset symptom location (\n              <jats:italic>p<\/jats:italic>\n              \u2009&lt;\u20090.001 for both outcomes) and initial DMT (\n              <jats:italic>p<\/jats:italic>\n              \u2009=\u20090.013 for PIRA;\n              <jats:italic>p<\/jats:italic>\n              \u2009=\u20090.022 for PIRMA).\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusion:<\/jats:title>\n            <jats:p>Women, especially postmenopausal, had higher PIRA\/PIRMA risk, but disability worsening per event was greater in men, associations varied by onset phenotype and initial DMT strategy.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1177\/17562864251376807","type":"journal-article","created":{"date-parts":[[2025,9,24]],"date-time":"2025-09-24T05:23:46Z","timestamp":1758691426000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":5,"title":["Sex differences in relapse-independent and relapse-associated disability progression in relapsing-remitting multiple sclerosis: a real-world inverse-probability weighted study"],"prefix":"10.1177","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0321-7155","authenticated-orcid":false,"given":"Matteo","family":"Foschi","sequence":"first","affiliation":[{"name":"Department of Neuroscience, Multiple Sclerosis Center\u2014Neurology Unit, S. Maria delle Croci Hospital, AUSL Romagna, Viale Vincenzo Randi 5, Ravenna 48121, Italy"},{"name":"Department of Biotechnological and Applied Clinical Sciences, University of L\u2019Aquila, L\u2019Aquila, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0358-9431","authenticated-orcid":false,"given":"Damiano","family":"Marastoni","sequence":"additional","affiliation":[{"name":"Neurology B, Department of Neurosciences, University of Verona, Verona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivan","family":"Panzera","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Multiple Sclerosis Center\u2014Neurology Unit, S. Maria delle Croci Hospital, AUSL Romagna, Ravenna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca","family":"Mancinelli","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Multiple Sclerosis Center\u2014Neurology Unit, Maurizio Bufalini Hospital, AUSL Romagna, Cesena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristiana","family":"Ganino","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Multiple Sclerosis Center\u2014Neurology Unit, Infermi Hospital, AUSL Romagna, Rimini, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gianmarco","family":"Abbadessa","sequence":"additional","affiliation":[{"name":"Department of Advanced Medical and Surgical Sciences, University of Campania \u201cLuigi Vanvitelli,\u201d Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6794-3850","authenticated-orcid":false,"given":"Lucio","family":"D\u2019Anna","sequence":"additional","affiliation":[{"name":"Department of Brain Sciences, Imperial College London, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Gabriele","sequence":"additional","affiliation":[{"name":"Department of Biotechnological and Applied Clinical Sciences, University of L\u2019Aquila, L\u2019Aquila, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simona","family":"Sacco","sequence":"additional","affiliation":[{"name":"Department of Biotechnological and Applied Clinical Sciences, University of L\u2019Aquila, L\u2019Aquila, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5753-6752","authenticated-orcid":false,"given":"Elisabetta","family":"Signoriello","sequence":"additional","affiliation":[{"name":"Second Division of Neurology, University of Campania \u201cLuigi Vanvitelli,\u201d Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandra","family":"Lugaresi","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Neuromotor Science, University of Bologna, Bologna, Italy"},{"name":"IRCCS Istituto delle Scienze Neurologiche di Bologna, Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Tsantes","sequence":"additional","affiliation":[{"name":"Neurology Unit, Department of General and Specialized Medicine, Parma University Hospital, Parma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Grazia","family":"Piscaglia","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Multiple Sclerosis Center\u2014Neurology Unit, S. Maria delle Croci Hospital, AUSL Romagna, Ravenna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Surcinelli","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Multiple Sclerosis Center\u2014Neurology Unit, S. 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