{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T18:41:35Z","timestamp":1785436895729,"version":"3.56.0"},"reference-count":44,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T00:00:00Z","timestamp":1780012800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Bristol Myers Squibb"},{"id":[{"id":"https:\/\/ror.org\/0433f0x41","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Relapsing\u2013remitting multiple sclerosis (RRMS) is characterized by neuroaxonal damage, astrogliosis and inflammation. These mechanisms may already be active from early disease stages, underscoring the need for sensitive biomarkers capable of capturing treatment-related biological effects beyond conventional clinical measures. In this multicenter, ambispective, observational real-world study, the longitudinal effects of ozanimod on serum biomarkers were evaluated, during the first year of treatment in patients with low-to-moderate activity RRMS. Serum neurofilament light chain (sNfL), glial fibrillary acidic protein (sGFAP) and cytokines associated with immune activity (IFN-\u03b3, IL-17, IL-6, IL-10, and IL-1\u03b2) were quantified at baseline, 6 months, and 12 months using an ultrasensitive single-molecule array (SIMOA). Ozanimod was associated with significant reductions in sNfLs and sGFAP at 12 months. Concomitantly, significant decreases in IFN-\u03b3 and IL-1\u03b2 were observed. IL-17 levels remained unchanged in the overall cohort but decreased in patients with higher baseline IL-17 levels. These findings demonstrate coordinated modulation of biomarkers reflecting neuroaxonal damage, astroglial activation, and inflammatory activity under ozanimod treatment in early RRMS in real-world conditions. These results highlight the biological relevance of early intervention within a therapeutic window of opportunity and support the potential utility of serum biomarkers for monitoring biological treatment effects in clinical practice.<\/jats:p>","DOI":"10.3390\/ijms27114933","type":"journal-article","created":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T12:45:08Z","timestamp":1780404308000},"page":"4933","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Ozanimod Reduces Serum Neurofilament Light Chain (NfL) and Glial Fibrillary Acidic Protein (GFAP) and Modulates Innate and Adaptive Immunity in Patients with Low-to-Moderate Activity Relapsing\u2013Remitting Multiple Sclerosis"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6512-4413","authenticated-orcid":false,"given":"Lucienne","family":"Costa-Frossard","sequence":"first","affiliation":[{"name":"Department of Neurology, Hospital Universitario Ram\u00f3n y Cajal, Red Espa\u00f1ola de Esclerosis, M\u00faltiple (REEM), Red de Enfermedades Inflamatorias (REI), IRYCIS, Universidad de Alcal\u00e1, 28034 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luis","family":"Brieva","sequence":"additional","affiliation":[{"name":"Neuroimmunology Group, Department of Medicine, Department of Neurology, University of Lleida, IRBLleida, Hospital Universitari Arnau de Vilanova, 25198 Lleida, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2968-5288","authenticated-orcid":false,"given":"Daniel Apolinar","family":"Garc\u00eda-Est\u00e9vez","sequence":"additional","affiliation":[{"name":"Department of Neurology, Complejo Hospitalario Universitario de Orense, 32005 Orense, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jes\u00fas Manuel","family":"Mart\u00edn-Mart\u00ednez","sequence":"additional","affiliation":[{"name":"Department of Neurology, Hospital Miguel Servet, 50009 Zaragoza, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gary","family":"\u00c1lvarez-Bravo","sequence":"additional","affiliation":[{"name":"Neuroimmunology and Multiple Sclerosis Unit, Neurodegeneration and Neuroinflammation Research Group, Girona Biomedical Research Institute (IDIBGI), Dr. Josep Trueta University Hospital, 17001 Girona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2719-4629","authenticated-orcid":false,"given":"Mar\u00eda Rosario","family":"Blasco-Qu\u00edlez","sequence":"additional","affiliation":[{"name":"Neuroimmunology Unit, Department of Medicine, Department of Neurology, University Autonoma de Madrid IRBLleida, Hospital Universitario Puerta de Hierro, 28222 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5050-9890","authenticated-orcid":false,"given":"Jos\u00e9 E.","family":"Meca-Lallana","sequence":"additional","affiliation":[{"name":"Multiple Sclerosis CSUR and Clinical Neuroimmunology Unit, Neurology Department, Virgen de la Arrixaca Clinical University Hospital (IMIB-Arrixaca), NICEM Cathedra-UCAM-San Antonio Catholic University, 30120 Murcia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda Carmen","family":"Calles-Hern\u00e1ndez","sequence":"additional","affiliation":[{"name":"Department of Neurology, Hospital Son Espases, 07120 Palma de Mallorca, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8643-5053","authenticated-orcid":false,"given":"Cristina","family":"Ramo Tello","sequence":"additional","affiliation":[{"name":"Multiple Sclerosis Unit, Department of Neurosciences, Germans Trias i Pujol 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Mar\u00eda","family":"Prieto Gonz\u00e1lez","sequence":"additional","affiliation":[{"name":"Department of Neurology, Complejo Hospitalario Universitario de Santiago, 15706 Santiago de Compostela, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9978-0198","authenticated-orcid":false,"given":"Antonio","family":"Candeliere-Merlicco","sequence":"additional","affiliation":[{"name":"Department of Neurology, Hospital Rafael M\u00e9ndez, 30817 Lorca, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5957-0046","authenticated-orcid":false,"given":"Olga","family":"Carmona","sequence":"additional","affiliation":[{"name":"Department of Neurology, Fundaci\u00f3 Salut Empord\u00e0, 17600 Girona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Javier","family":"Riancho","sequence":"additional","affiliation":[{"name":"Department of Medicine and Psychiatry, University of Cantabria, 39005 Santander, Spain"},{"name":"Service of Neurology, Hospital General Sierrallana-IDIVAL, 39300 Torrelavega, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nuria","family":"Sola-Valls","sequence":"additional","affiliation":[{"name":"Clinical and Epidemiological Neuroscience Group (Neuro\u00c8pia) IRBCatSud, Department of Neurology, Hospital Sant Joan de Reus, 43204 Reus, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda","family":"Carcel\u00e9n-Gadea","sequence":"additional","affiliation":[{"name":"Department of Neurology, Hospital General Universitario de Valencia, 46014 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1425-1789","authenticated-orcid":false,"given":"Laura","family":"Borrega","sequence":"additional","affiliation":[{"name":"Neurology Unit, Hospital Universitario Fundaci\u00f3n Alcorc\u00f3n, 28922 Alcorc\u00f3n, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5171-9910","authenticated-orcid":false,"given":"Francisco","family":"Gasc\u00f3n-Gim\u00e9nez","sequence":"additional","affiliation":[{"name":"Department of Neurology, Hospital Cl\u00ednico Universitario de Valencia, 46010 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Vilanova","sequence":"additional","affiliation":[{"name":"Bristol Myers Squibb, 28050 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xavier","family":"P\u00e9rez","sequence":"additional","affiliation":[{"name":"Bristol Myers Squibb, 28050 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luisa Mar\u00eda","family":"Villar","sequence":"additional","affiliation":[{"name":"Department of Immunology, Hospital Universitario Ram\u00f3n y Cajal, Red Espa\u00f1ola de Esclerosis M\u00faltiple (REEM), Red de Enfermedades 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