{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T02:25:57Z","timestamp":1790821557801,"version":"4.1.0"},"reference-count":38,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2024,11,23]],"date-time":"2024-11-23T00:00:00Z","timestamp":1732320000000},"content-version":"vor","delay-in-days":327,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100021515","name":"Sanofi","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100021515","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,10,30]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Currently, there are limited therapeutic options for patients with non-active secondary progressive multiple sclerosis. Therefore, real-world studies have investigated differences between patients with relapsing-remitting multiple sclerosis, non-active secondary progressive multiple sclerosis and active secondary progressive multiple sclerosis. Here, we explore patterns and predictors of transitioning between these phenotypes. We performed a cohort study using data from The Danish Multiple Sclerosis Registry. We included patients with a relapsing-remitting phenotype, registered changes to secondary progressive multiple sclerosis and subsequent transitions between relapsing and non-relapsing secondary progressive multiple sclerosis, which was defined by the presence of relapses in the previous 2 years. We analysed predictors of transitioning from relapsing-remitting multiple sclerosis to relapsing and non-relapsing secondary progressive multiple sclerosis, as well as between the secondary progressive states using a multi-state Markov model. We included 4413 patients with relapsing-remitting multiple sclerosis. Within a median follow-up of 16.2\u2005years, 962 were diagnosed with secondary progressive multiple sclerosis by their treating physician. Of these, we classified 729 as non-relapsing and 233 as relapsing secondary progressive multiple sclerosis. The risk of transitioning from relapsing-remitting to non-relapsing secondary progressive multiple sclerosis included older age (hazard ratio per increase of 1\u2005year in age: 1.044, 95% confidence interval: 1.035\u20131.053), male sex (hazard ratio for female: 0.735, 95% confidence interval: 0.619\u20130.874), fewer relapses (hazard ratio per each additional relapse: 0.863, 95% confidence interval: 0.823\u20130.906), higher expanded disability status scale (hazard ratio per each additional point: 1.522, 95% confidence interval: 1.458\u20131.590) and longer time on disease-modifying therapies (hazard ratio per increase of 1\u2005year in treatment, high-efficacy disease-modifying therapy: 1.095, 95% confidence interval: 1.051\u20131.141; hazard ratio, moderate-efficacy disease-modifying therapy: 1.073, 95% confidence interval: 1.051\u20131.095). We did not find significant predictors associated with the transition from relapsing secondary progressive multiple sclerosis to non-relapsing secondary progressive multiple sclerosis, whereas older age (hazard ratio per increase of 1\u2005year in age: 0.956, 95% confidence interval: 0.942\u20130.971) prevented the transition from non-relapsing secondary progressive multiple sclerosis to relapsing secondary progressive multiple sclerosis. Our study suggests that transitioning from relapsing-remitting multiple sclerosis to non-relapsing secondary progressive multiple sclerosis depends on well-known factors affecting diagnosing secondary progressive multiple sclerosis. Further transitions between non-relapsing and relapsing secondary progressive multiple sclerosis are only affected by age. These findings add to the knowledge of non-active secondary progressive multiple sclerosis, a patient group with unmet needs in terms of therapies.<\/jats:p>","DOI":"10.1093\/braincomms\/fcae422","type":"journal-article","created":{"date-parts":[[2024,11,21]],"date-time":"2024-11-21T07:18:43Z","timestamp":1732173523000},"source":"Crossref","is-referenced-by-count":11,"title":["Patterns and predictors of multiple sclerosis phenotype transition"],"prefix":"10.1093","volume":"6","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1506-3827","authenticated-orcid":false,"given":"Luigi","family":"Pontieri","sequence":"first","affiliation":[{"name":"The Danish Multiple Sclerosis Registry, Department of Neurology, Copenhagen University Hospital\u2014Rigshospitalet Glostrup , 2600 Glostrup ,","place":["Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nupur","family":"Greene","sequence":"additional","affiliation":[{"name":"Sanofi , Cambridge, MA 02141 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7455-4829","authenticated-orcid":false,"given":"Malthe Faurschou","family":"Wandall-Holm","sequence":"additional","affiliation":[{"name":"The Danish Multiple Sclerosis Registry, Department of Neurology, Copenhagen University Hospital\u2014Rigshospitalet Glostrup , 2600 Glostrup ,","place":["Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4497-3616","authenticated-orcid":false,"given":"Svend Sparre","family":"Geertsen","sequence":"additional","affiliation":[{"name":"Sanofi , Cambridge, MA 02141 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8551-0947","authenticated-orcid":false,"given":"Nasrin","family":"Asgari","sequence":"additional","affiliation":[{"name":"Department of Neurology, Naestved, Slagelse and Ringsted Hospitals , 4200 Slagelse ,","place":["Denmark"]},{"name":"Department of Regional Health Research, University of Southern Denmark , 5000 Odense ,","place":["Denmark"]},{"name":"Department of Molecular Medicine, University of Southern Denmark , 5000 Odense ,","place":["Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6461-3787","authenticated-orcid":false,"given":"Henrik Boye","family":"Jensen","sequence":"additional","affiliation":[{"name":"Department of Regional Health Research, University of Southern Denmark , 5000 Odense ,","place":["Denmark"]},{"name":"Department of Brain and Nerve Diseases, Lilleb\u00e6lt Hospital , 6000 Kolding ,","place":["Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9655-0450","authenticated-orcid":false,"given":"Zsolt","family":"Illes","sequence":"additional","affiliation":[{"name":"Department of Neurology, Odense University Hospital , 5000 Odense ,","place":["Denmark"]},{"name":"Department of Clinical Research, University of Southern Denmark , 5000 Odense ,","place":["Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2562-1818","authenticated-orcid":false,"given":"Jakob","family":"Sch\u00e4fer","sequence":"additional","affiliation":[{"name":"Department of Neurology, Aalborg University Hospital , 9100 Aalborg ,","place":["Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rikke Marie","family":"Jensen","sequence":"additional","affiliation":[{"name":"Danish Multiple Sclerosis Center, Department of Neurology, Copenhagen University Hospital\u2014Rigshospitalet Glostrup , 2600 Glostrup ,","place":["Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7682-2188","authenticated-orcid":false,"given":"Tobias","family":"Sejb\u00e6k","sequence":"additional","affiliation":[{"name":"Department of Regional Health Research, University of Southern Denmark , 5000 Odense ,","place":["Denmark"]},{"name":"Department of Neurology, Southwest Jutland Hospital, University Hospital of Southern Denmark , 6700 Esbjerg ,","place":["Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arkadiusz","family":"Weglewski","sequence":"additional","affiliation":[{"name":"Department of Neurology, Herlev and Gentofte Hospital , 2730 Herlev ,","place":["Denmark"]},{"name":"Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen , 2200 Copenhagen ,","place":["Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0484-8220","authenticated-orcid":false,"given":"Mie Reith","family":"Mahler","sequence":"additional","affiliation":[{"name":"The Danish Multiple Sclerosis Registry, Department of Neurology, Copenhagen University Hospital\u2014Rigshospitalet Glostrup , 2600 Glostrup ,","place":["Denmark"]},{"name":"Danish Multiple Sclerosis Center, Department of Neurology, Copenhagen University Hospital\u2014Rigshospitalet Glostrup , 2600 Glostrup ,","place":["Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5525-0678","authenticated-orcid":false,"given":"Mai Bang","family":"Poulsen","sequence":"additional","affiliation":[{"name":"Department of Neurology, Copenhagen University Hospital\u2014North Zealand , 3400 Hiller\u00f8d ,","place":["Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sivagini","family":"Prakash","sequence":"additional","affiliation":[{"name":"Department of Neurology, Viborg Regional Hospital , 8800 Viborg ,","place":["Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-2255-3380","authenticated-orcid":false,"given":"Morten","family":"Stilund","sequence":"additional","affiliation":[{"name":"Department of Neurology, Physiotherapy and Occupational Therapy, G\u00f8dstrup Hospital , 7400 Herning ,","place":["Denmark"]},{"name":"NIDO | Centre for Research and Education, G\u00f8dstrup Hospital , 7400 Herning ,","place":["Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5090-8234","authenticated-orcid":false,"given":"Matthias","family":"Kant","sequence":"additional","affiliation":[{"name":"Department of Neurology, Southern Jutland Hospital, University of Southern Denmark , 6200 Aabenraa ,","place":["Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6417-7743","authenticated-orcid":false,"given":"Peter Vestergaard","family":"Rasmussen","sequence":"additional","affiliation":[{"name":"Department of Neurology, Aarhus University Hospital , 8200 Aarhus N ,","place":["Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristina Bacher","family":"Svendsen","sequence":"additional","affiliation":[{"name":"Department of Neurology, Aarhus University Hospital , 8200 Aarhus N ,","place":["Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1333-9623","authenticated-orcid":false,"given":"Finn","family":"Sellebjerg","sequence":"additional","affiliation":[{"name":"Danish Multiple Sclerosis Center, Department of Neurology, Copenhagen University Hospital\u2014Rigshospitalet Glostrup , 2600 Glostrup ,","place":["Denmark"]},{"name":"Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen , 2200 Copenhagen ,","place":["Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0972-5222","authenticated-orcid":false,"given":"Melinda","family":"Magyari","sequence":"additional","affiliation":[{"name":"The Danish Multiple Sclerosis Registry, Department of Neurology, Copenhagen University Hospital\u2014Rigshospitalet Glostrup , 2600 Glostrup ,","place":["Denmark"]},{"name":"Danish Multiple Sclerosis Center, Department of Neurology, Copenhagen University Hospital\u2014Rigshospitalet Glostrup , 2600 Glostrup ,","place":["Denmark"]},{"name":"Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen , 2200 Copenhagen ,","place":["Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2024,11,23]]},"reference":[{"key":"2024122016280003000_fcae422-B1","author":"Multiple Sclerosis International Federation\u2014Atlas of MS"},{"issue":"4","key":"2024122016280003000_fcae422-B2","doi-asserted-by":"crossref","first-page":"907","DOI":"10.1212\/WNL.46.4.907","article-title":"Defining the clinical course of multiple sclerosis: Results of an international survey. 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(EDSS)","volume":"33","author":"Kurtzke","year":"1983","journal-title":"Neurology"},{"key":"2024122016280003000_fcae422-B19","author":"R Core Team"},{"issue":"3","key":"2024122016280003000_fcae422-B20","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1093\/biomet\/80.3.557","article-title":"Checking the cox model with cumulative sums of martingale-based residuals","volume":"80","author":"Lin","year":"1993","journal-title":"Biometrika"},{"issue":"8","key":"2024122016280003000_fcae422-B21","doi-asserted-by":"crossref","first-page":"1","DOI":"10.18637\/jss.v038.i08","article-title":"Multi-state models for panel data: The msm package for R","volume":"38","author":"Jackson","year":"2011","journal-title":"J Stat Softw"},{"issue":"9","key":"2024122016280003000_fcae422-B22","doi-asserted-by":"crossref","first-page":"3147","DOI":"10.1093\/brain\/awac016","article-title":"How patients with multiple sclerosis acquire 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