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We aimed to describe disease activity and treatment trajectories in patients with MS who de\u2010escalated from an HE DMT to an moderate\u2010efficacy (ME) DMT.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We performed a cohort study based on data from the Danish Multiple Sclerosis Registry (DMSR) including patients with relapsing\u2013remitting MS (RRMS), who switched from an HE DMT to an ME DMT as defined by Danish authorities. We included patients from October 2007 to July 2023. Median follow\u2010up time was 0.8\u2009years (IQR 0.3\u20132.5).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In total 333 patients (76.0% females, mean age: 45.1\u2009years) de\u2010escalated for various reasons. Most patients de\u2010escalated from natalizumab or fingolimod (43.8% and 42.0%, respectively) to dimethyl fumarate (47.5%). At 2\u2009years after de\u2010escalation, the cumulative risk of relapse was 38% (95% CI 31\u201344) and 53% (95% CI 46\u201360) for inflammatory disease activity (relapses and\/or radiological disease activity). Age (HR 0.96, 95% CI 0.94\u20130.98) and inflammatory disease activity prior to de\u2010escalation (HR 2.05, 95% CI 1.45\u20132.91) were associated with inflammatory disease activity post de\u2010escalation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>De\u2010escalation from primarily natalizumab and fingolimod did not effectively ensure disease stability in this cohort. Younger age and inflammatory disease activity prior to de\u2010escalation were risk factors for inflammatory disease activity post de\u2010escalation, which can help guide future studies on de\u2010escalation.<\/jats:p><\/jats:sec>","DOI":"10.1111\/ene.70042","type":"journal-article","created":{"date-parts":[[2025,2,3]],"date-time":"2025-02-03T07:39:51Z","timestamp":1738568391000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["De\u2010Escalation of Disease\u2010Modifying Therapy in Multiple Sclerosis\u2014A Danish Nationwide Cohort Study"],"prefix":"10.1111","volume":"32","author":[{"given":"Frederik","family":"Elberling","sequence":"first","affiliation":[{"name":"The Danish Multiple Sclerosis Registry, Danish Multiple Sclerosis Center, Department of Neurology Copenhagen University Hospital \u2013 Rigshospitalet  Glostrup 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, Danish Multiple Sclerosis Center, Department of Neurology Copenhagen University Hospital \u2013 Rigshospitalet  Glostrup Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1506-3827","authenticated-orcid":false,"given":"Luigi","family":"Pontieri","sequence":"additional","affiliation":[{"name":"The Danish Multiple Sclerosis Registry, Danish Multiple Sclerosis Center, Department of Neurology Copenhagen University Hospital \u2013 Rigshospitalet  Glostrup Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Finn","family":"Sellebjerg","sequence":"additional","affiliation":[{"name":"The Danish Multiple Sclerosis Registry, Danish Multiple Sclerosis Center, Department of Neurology Copenhagen University Hospital \u2013 Rigshospitalet  Glostrup Denmark"},{"name":"Department of Clinical Medicine University of Copenhagen  Copenhagen 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, Danish Multiple Sclerosis Center, Department of Neurology Copenhagen University Hospital \u2013 Rigshospitalet  Glostrup Denmark"},{"name":"Department of Clinical Medicine University of Copenhagen  Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"for the DMSG Study Group","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,2,2]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41572\u2010018\u20100041\u20104"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474\u20104422(20)30063\u20106"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1097\/WCO.0000000000000937"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000010135"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp\u20102022\u2010329058"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1080\/14737175.2023.2208347"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00415\u2010024\u201012584\u2010x"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41582\u2010019\u20100183\u20103"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/ene.12690"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11940\u2010021\u201000662\u20108"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2017.00577"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1097\/WCO.0000000000000701"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2021.799138"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11910\u2010024\u201001355\u2010w"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/brb3.1921"},{"key":"e_1_2_10_17_1","unstructured":"Medicinr\u00e5det Medicinr\u00e5dets L\u00e6gemiddelrekommandation Vedr. 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