{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T00:20:49Z","timestamp":1791073249016,"version":"4.1.0"},"reference-count":148,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,3,21]],"date-time":"2025-03-21T00:00:00Z","timestamp":1742515200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Approximately 50% diagnosed with relapsing-remitting multiple sclerosis (RRMS) transition to secondary progressive multiple sclerosis (SPMS) within 20 years following disease onset. However, early diagnosis of SPMS and effective treatment remain important clinical challenges. The lack of established diagnostic criteria often leads to delays in identifying SPMS. Also, there are limited disease-modifying therapies (DMTs) available for progressive forms of MS, and these therapies require evidence of disease activity to be initiated. This review examines the challenges in diagnosing SPMS at an early stage and summarizes the current and potential use of biomarkers of disease progression in clinical practice. We also discuss the difficulties in initiating the DMTs indicated for active SPMS (aSPMS), particularly in patients already undergoing treatment with DMTs that suppress disease activity, which may mask the presence of inflammatory activity required for the therapy switch. The article also addresses the DMTs available for both active and non-active SPMS, along with the clinical trials that supported the approval of DMTs indicated for aSPMS or relapsing MS in Europe, which includes aSPMS. We also offer insights on when discontinuing these treatments may be appropriate.<\/jats:p>","DOI":"10.3389\/fimmu.2025.1543649","type":"journal-article","created":{"date-parts":[[2025,3,21]],"date-time":"2025-03-21T01:21:03Z","timestamp":1742520063000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":19,"title":["Current challenges in secondary progressive multiple sclerosis: diagnosis, activity detection and treatment"],"prefix":"10.3389","volume":"16","author":[{"given":"Luis","family":"Brieva","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmen","family":"Calles","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lamberto","family":"Landete","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Celia","family":"Oreja-Guevara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,3,21]]},"reference":[{"key":"B1","unstructured":"Epidemiology\n          \n          2024"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1177\/1352458517708672","article-title":"New insights into the burden and costs of multiple sclerosis in Europe: Results for Spain","volume":"23","author":"Oreja-Guevara","year":"2017","journal-title":"Multiple Sclerosis J"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-022-11169-w","article-title":"Patients with multiple sclerosis: a burden and cost of illness study","volume":"269","author":"Battaglia","year":"2022","journal-title":"J Neurol"},{"key":"B4","doi-asserted-by":"publisher","first-page":"105787","DOI":"10.1016\/j.msard.2024.105787","article-title":"Clinical characteristics and impact on patient-reported outcomes and quality of life of people with ambulatory secondary progressive multiple sclerosis: DISCOVER study","volume":"90","author":"Oreja-Guevara","year":"2024","journal-title":"Multiple Sclerosis Related Disord"},{"key":"B5","doi-asserted-by":"publisher","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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