{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T23:39:36Z","timestamp":1777937976761,"version":"3.51.4"},"reference-count":32,"publisher":"SAGE Publications","issue":"10","license":[{"start":{"date-parts":[[2025,7,23]],"date-time":"2025-07-23T00:00:00Z","timestamp":1753228800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2025,7,23]],"date-time":"2025-07-23T00:00:00Z","timestamp":1753228800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"name":"Bristol Myers Squibb"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Mult Scler"],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>In phase 3 trials, ozanimod reduced brain atrophy and improved cognitive processing speed compared with interferon \u03b2-1a (IFN) in participants with relapsing multiple sclerosis (RMS).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives:<\/jats:title>\n                    <jats:p>To assess long-term brain volume changes and associations with clinical\/cognitive outcomes during an open-label extension ([OLE] DAYBREAK [NCT02576717]).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>Completers of phase 3 \u201cparent\u201d trials were eligible to receive ozanimod 0.92 mg in DAYBREAK. Whole brain, thalamic, and cortical gray matter volumes (WBV, TV, and CGMV, respectively) were analyzed annually.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>Participants receiving continuous ozanimod had sustained, low rates of WBV loss through OLE month (M)60 (annualized least-squares mean percent change from parent baseline: RADIANCE, \u22120.27; SUNBEAM, \u22120.35). Compared with participants switched from IFN, these participants had lower reductions in WBV (parent baseline through OLE M48 [RADIANCE] and OLE M60 [SUNBEAM]). Larger baseline brain volumes were associated with numerically better Symbol Digit Modalities Test scores and lower 3-month confirmed disability progression (CDP) incidence. Annualized TV atrophy \u2a7d1.0% was associated with lower 3-month CDP.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>This study confirms the sustained efficacy of ozanimod in reducing brain atrophy rates for up to 7 years. Brain volume preservation was associated with faster cognitive processing speed and slower physical disability progression.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/13524585251355842","type":"journal-article","created":{"date-parts":[[2025,7,23]],"date-time":"2025-07-23T10:55:21Z","timestamp":1753268121000},"page":"1218-1230","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Brain atrophy and associations with long-term disability and cognitive function in participants with relapsing multiple sclerosis treated with ozanimod: Results from phase 3 and open-label extension trials"],"prefix":"10.1177","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9245-9772","authenticated-orcid":false,"given":"Jeffrey A","family":"Cohen","sequence":"first","affiliation":[{"name":"Mellen Center for MS Treatment and Research, Cleveland Clinic, Cleveland, OH, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4266-0106","authenticated-orcid":false,"given":"Douglas L","family":"Arnold","sequence":"additional","affiliation":[{"name":"NeuroRx Research and Montr\u00e9al Neurological Institute, McGill University, Montr\u00e9al, QC, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3745-4156","authenticated-orcid":false,"given":"John","family":"DeLuca","sequence":"additional","affiliation":[{"name":"Kessler Foundation, West Orange, NJ, USA"},{"name":"Department of Physical Medicine &amp; Rehabilitation and Department of Neurology &amp; Neurosciences, Rutgers\u2014New Jersey Medical School, Newark, NJ, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hans-Peter","family":"Hartung","sequence":"additional","affiliation":[{"name":"Department of Neurology, Medical Faculty, Heinrich Heine University, D\u00fcsseldorf, Germany"},{"name":"Brain and Mind Centre, University of Sydney, Camperdown, NSW, Australia"},{"name":"Department of Neurology, Medical University of Vienna, Vienna, Austria"},{"name":"Department of Neurology, Palack\u00fd University Olomouc, Olomouc, Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4175-5509","authenticated-orcid":false,"given":"Ludwig","family":"Kappos","sequence":"additional","affiliation":[{"name":"Research Center for Clinical Neuroimmunology and Neuroscience Basel (RC2NB), Departments of Head Organs, Spine and Neuromedicine, Clinical Research, Biomedicine, and Biomedical Engineering, University Hospital and University of Basel, Basel, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giancarlo","family":"Comi","sequence":"additional","affiliation":[{"name":"Vita-Salute San Raffaele University and Casa di Cura Igea, Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Krzysztof","family":"Selmaj","sequence":"additional","affiliation":[{"name":"Center for Neurology, \u0141\u00f3d\u017a, Poland"},{"name":"Collegium Medicum, Department of Neurology, University of Warmia and Mazury, Olsztyn, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lawrence","family":"Steinman","sequence":"additional","affiliation":[{"name":"Department of Neurology and Neurological Sciences, Beckman Center for Molecular Medicine, Stanford University Medical Center, Stanford, CA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7179-0335","authenticated-orcid":false,"given":"Amit","family":"Bar-Or","sequence":"additional","affiliation":[{"name":"Center for Neuroinflammation and Experimental Therapeutics, and Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xavier","family":"Montalban","sequence":"additional","affiliation":[{"name":"Department of Neurology, Centre d\u2019Esclerosi M\u00faltiple de Catalunya (Cemcat), Hospital Universitari Vall d\u2019Hebron, Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eva K","family":"Havrdov\u00e1","sequence":"additional","affiliation":[{"name":"Department of Neurology and Center for Clinical Neuroscience, First Medical Faculty and General University Hospital, Charles University, Prague, Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James K","family":"Sheffield","sequence":"additional","affiliation":[{"name":"Bristol Myers Squibb, Princeton, NJ, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chahin","family":"Pachai","sequence":"additional","affiliation":[{"name":"Bristol Myers Squibb, Princeton, NJ, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chun-Yen","family":"Cheng","sequence":"additional","affiliation":[{"name":"Bristol Myers Squibb, Princeton, NJ, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jon V","family":"Riolo","sequence":"additional","affiliation":[{"name":"Bristol Myers Squibb, Princeton, NJ, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7689-2533","authenticated-orcid":false,"given":"Bruce AC","family":"Cree","sequence":"additional","affiliation":[{"name":"Weill Institute for Neurosciences, Department of Neurology, University of California San Francisco, San Francisco, CA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2025,7,23]]},"reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41572-018-0041-4"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(18)30481-1"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1401483"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1007\/s40263-014-0140-z"},{"key":"e_1_3_3_6_2","first-page":"93","article-title":"Establishing pathological cut-offs of brain atrophy rates in multiple sclerosis","volume":"87","author":"De Stefano N","year":"2016","unstructured":"De Stefano N, Stromillo ML, Giorgio A, et al. Establishing pathological cut-offs of brain atrophy rates in multiple sclerosis. J Neurol Neurosurg Psychiatry 2016; 87: 93\u201399.","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"e_1_3_3_7_2","article-title":"Brain health: Time matters in multiple sclerosis","volume":"9","author":"Giovannoni G","year":"2016","unstructured":"Giovannoni G, Butzkueven H, Dhib-Jalbut S, et al. Brain health: Time matters in multiple sclerosis. Mult Scler Relat Disord 2016; 9 Suppl. 1: S5\u2013S48.","journal-title":"Mult Scler Relat Disord"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp.73.2.141"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2022.1025"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1177\/1352458515616701"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.98.18_supplement.839"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.25145"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1177\/13524585231162586"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2020.00606"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.25150"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1177\/1352458514537012"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1177\/13524585211011390"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.rehab.2022.101677"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1177\/13524585211066598"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1177\/1352458515599075"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1590\/0004-282X20160015"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-011-6147-1"},{"key":"e_1_3_3_23_2","unstructured":"Zeposia [package insert]. Princeton NJ: Bristol Myers Squibb 2024."},{"key":"e_1_3_3_24_2","unstructured":"Zeposia [summary of product characteristics]. Dublin: Bristol-Myers Squibb Pharma 2024."},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(19)30238-8"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(19)30239-X"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1177\/13524585221102584"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1177\/1352458517690821"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jns.2017.08.019"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jns.2009.02.379"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awab132"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-014-1787-9"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(18)30475-6"}],"container-title":["Multiple Sclerosis Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/13524585251355842","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/13524585251355842","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/13524585251355842","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,2]],"date-time":"2026-05-02T04:18:57Z","timestamp":1777695537000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/13524585251355842"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,23]]},"references-count":32,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2025,9]]}},"alternative-id":["10.1177\/13524585251355842"],"URL":"https:\/\/doi.org\/10.1177\/13524585251355842","relation":{},"ISSN":["1352-4585","1477-0970"],"issn-type":[{"value":"1352-4585","type":"print"},{"value":"1477-0970","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,23]]}}}