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REVIEW article

Front. Immunol.

Sec. Multiple Sclerosis and Neuroimmunology

Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1543649

Current Challenges in Secondary Progressive Multiple Sclerosis: Diagnosis, Activity Detection and Treatment

Provisionally accepted
  • 1 Neurology Department, Hospital Universitari Arnau de Vilanova, Lleida, Spain
  • 2 Universitat de Lleida, Lleida, Catalonia, Spain
  • 3 Institut de Recerca Biomedica de Lleida (IRBLLEIDA), Lleida, Spain
  • 4 Neurology Department, Hospital Universitario Son Espases, Palma de Mallorca, Spain
  • 5 Neurology Department, Hospital Universitario Doctor Peset, Valencia, Spain
  • 6 Servicio de NeurologĂ­a, Hospital ClĂ­nico San Carlos, Madrid, Spain
  • 7 Departament of Medicine, Medicine Faculty, Universidad Complutense de Madrid (UCM), Madrid, Spain

The final, formatted version of the article will be published soon.

    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 29 treatments may be appropriate. 30

    Keywords: Silent progression, smouldering disease, Secondary progressive multiple sclerosis, Multiple sclerosis treatment, disease activity, disease-modifying treatments, Multiple Sclerosis

    Received: 11 Dec 2024; Accepted: 25 Feb 2025.

    Copyright: © 2025 Brieva, Calles, Pascual and Oreja-Guevara. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Celia Oreja-Guevara, Servicio de NeurologĂ­a, Hospital ClĂ­nico San Carlos, Madrid, Spain

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.

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