{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T16:18:28Z","timestamp":1792685908751,"version":"4.5.0"},"reference-count":39,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2026,2,28]],"date-time":"2026-02-28T00:00:00Z","timestamp":1772236800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,2,28]],"date-time":"2026-02-28T00:00:00Z","timestamp":1772236800000},"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":[[2026,3]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>Siponimod, a selective sphingosine-1-phosphate receptor modulator was approved for patients with Secondary progressive Multiple Sclerosis (SPMS) with ongoing disease activity. However, its real-world positioning and management after discontinuation remain challenging.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives:<\/jats:title>\n                    <jats:p>To evaluate the real-world use of siponimod in Italian real world setting, focusing on discontinuation rates, possible predictors, and post-treatment management.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>A retrospective, multicenter study on patients treated with siponimod across six Italian MS centers. Demographics, prior disease modifying therapy (DMTs), reasons for discontinuation, adverse events, and subsequent therapies were collected. Statistical analyses included propensity-adjusted Cox model.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      A total cohort of 188 patients (63.8% female, median age 52\u2009years) was enrolled, out of them 76(40.4%) discontinued siponimod, with a median treatment duration of 26\u2009months. The main reason for discontinuation was safety concerns (72.4%), particularly persistent lymphopenia (43.6%) and recurrent infections (27.3%). Disease activity accounted for 27.6% of discontinuations. No significant demographic or clinical predictors of discontinuation were identified. After discontinuation, 49 patients (64%) started a new DMT, most commonly ocrelizumab (\n                      <jats:italic toggle=\"yes\">n<\/jats:italic>\n                      \u2009=\u200922) or cladribine (\n                      <jats:italic toggle=\"yes\">n<\/jats:italic>\n                      \u2009=\u200915), while 25 (32.9%) received no further therapy.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>High discontinuation rates, mainly due to safety, and frequent post-treatment gaps highlight the need for improved, individualized management strategies for SPMS after siponimod.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/17562864251399560","type":"journal-article","created":{"date-parts":[[2026,2,28]],"date-time":"2026-02-28T12:31:33Z","timestamp":1772281893000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":1,"title":["Positioning siponimod and the post-treatment gap: the unmet needs of SPMS patients in Italian real-world practice"],"prefix":"10.1177","volume":"19","author":[{"given":"Aurora","family":"Zangh\u00ec","sequence":"first","affiliation":[{"name":"Department of Medical and Surgical Sciences, University of Foggia, Foggia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanna","family":"Borriello","sequence":"additional","affiliation":[{"name":"Fatebenefratelli Hospital, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0321-7155","authenticated-orcid":false,"given":"Matteo","family":"Foschi","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, MS Center\u2014Neurology Unit, S.Maria delle Croci Hospital, AUSL Romagna, Ravenna, Italy"},{"name":"Department of Biotechnological and Applied Clinical Sciences, University of L\u2019Aquila, L\u2019Aquila, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Assunta","family":"Bianco","sequence":"additional","affiliation":[{"name":"Multiple Sclerosis Center, Fondazione Policlinico Universitario \u201cA. 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Gemelli\u201d IRCCS, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giacomo","family":"Lus","sequence":"additional","affiliation":[{"name":"Multiple Sclerosis Centre, II Division of Neurology, Department of Clinical and Experimental Medicine, University of Campania Luigi Vanvitelli, Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matilde","family":"Inglese","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, and Mother-Child Health, University of Genoa, Genoa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Massimiliano","family":"Mirabella","sequence":"additional","affiliation":[{"name":"Multiple Sclerosis Center, Fondazione Policlinico Universitario \u201cA. 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