{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T11:50:42Z","timestamp":1788263442531,"version":"build-2803163510"},"reference-count":156,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2025,8,11]],"date-time":"2025-08-11T00:00:00Z","timestamp":1754870400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Next Generation EU\u2013NRRP M6C2\u2013Investment 2.1 Enhancement and Strengthening of Biomedical Research in the NHS","award":["PNRR-MAD-2022-12376868"],"award-info":[{"award-number":["PNRR-MAD-2022-12376868"]}]},{"name":"Italian National Recovery and Resilience Plan","award":["PNRR-MAD-2022-12376868"],"award-info":[{"award-number":["PNRR-MAD-2022-12376868"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Multiple sclerosis (MS) is characterized by a continuum of diverse neuroinflammatory and neurodegenerative processes that contribute to disease progression from the earliest stages. This leads to a highly heterogeneous clinical course, requiring early and accurate prognostic assessment: the identification of reliable prognostic biomarkers is crucial to support therapeutic decision-making and guide personalized disease management. In this narrative review, we critically examined the current MS literature, investigating prognostic factors associated with disease progression and irreversible disability in adult-onset MS, with a focus on different clinical, radiological, and molecular biomarkers. Particular attention is directed toward the prognostic value of baseline clinical and neuroimaging factors, emerging biomarkers of smoldering disease, and progression independent of relapse activity (PIRA) events. Additionally, we discussed the role of integrated prognostic tools and risk scores, as well as their potential impact on clinical practice. We aim to provide a comprehensive and clinically oriented synthesis of available evidence in the MS biomarkers field, supporting multifaceted prognostication strategies to improve long-term outcomes in people with MS.<\/jats:p>","DOI":"10.3390\/ijms26167756","type":"journal-article","created":{"date-parts":[[2025,8,11]],"date-time":"2025-08-11T14:32:36Z","timestamp":1754922756000},"page":"7756","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Refining Prognostic Factors in Adult-Onset Multiple Sclerosis: A Narrative Review of Current Insights"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5248-5981","authenticated-orcid":false,"given":"Tommaso","family":"Guerra","sequence":"first","affiliation":[{"name":"Department of Translational Biomedicine and Neurosciences-DiBraiN, University of Bari \u201cAldo Moro\u201d, Azienda Ospedaliero-Universitaria Consorziale Policlinico di Bari, 70100 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Massimiliano","family":"Copetti","sequence":"additional","affiliation":[{"name":"Unit of Biostatistics, Fondazione IRCCS \u201cCasa Sollievo della Sofferenza\u201d, 71013 San Giovanni Rotondo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariaclara","family":"Achille","sequence":"additional","affiliation":[{"name":"Department of Translational Biomedicine and Neurosciences-DiBraiN, University of Bari \u201cAldo Moro\u201d, Azienda Ospedaliero-Universitaria Consorziale Policlinico di Bari, 70100 Bari, Italy"},{"name":"Child Neuropsychiatry Unit, Department of Precision and Regenerative Medicine, Jonic Area University of Bari \u201cAldo Moro\u201d, 70100 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8699-7283","authenticated-orcid":false,"given":"Caterina","family":"Ferri","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, S. 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