Disease-modifying therapies for relapsing/active secondary progressive multiple sclerosis: a review of population-specific evidence from randomized clinical trials

  • Although the understanding of secondary progressive multiple sclerosis (SPMS) is evolving, early detection of relapse-independent progression remains difficult. This is further complicated by superimposed relapses and compensatory mechanisms that allow for silent progression. The term relapsing multiple sclerosis (RMS) subsumes relapsing-remitting multiple sclerosis (RRMS) and SPMS with relapses. The latter is termed ‘active’ SPMS, for which disease-modifying therapies (DMTs) approved for either RMS or active SPMS can be used. However, the level of evidence supporting efficacy and safety in SPMS differs between drugs approved for RMS and SPMS. Our review aims to identify current evidence from published clinical trials and European public assessment reports from the marketing authorization procedure on the efficacy, especially on progression, of DMTs approved for RMS and SPMS. To identify relevant evidence, a literature search has been conducted and European public assessment reports ofAlthough the understanding of secondary progressive multiple sclerosis (SPMS) is evolving, early detection of relapse-independent progression remains difficult. This is further complicated by superimposed relapses and compensatory mechanisms that allow for silent progression. The term relapsing multiple sclerosis (RMS) subsumes relapsing-remitting multiple sclerosis (RRMS) and SPMS with relapses. The latter is termed ‘active’ SPMS, for which disease-modifying therapies (DMTs) approved for either RMS or active SPMS can be used. However, the level of evidence supporting efficacy and safety in SPMS differs between drugs approved for RMS and SPMS. Our review aims to identify current evidence from published clinical trials and European public assessment reports from the marketing authorization procedure on the efficacy, especially on progression, of DMTs approved for RMS and SPMS. To identify relevant evidence, a literature search has been conducted and European public assessment reports of DMTs approved for RMS have been screened for unpublished data specific to SPMS. Only two clinical trials demonstrated a significant reduction in disability progression in SPMS study populations: the EXPAND study for siponimod, which included a typical SPMS population, and the European study for interferon (IFN)-beta 1b s.c., which included patients with very early and active SPMS. Both DMTs also achieved significant reductions in relapse rates. Ocrelizumab, cladribine, ofatumumab, and ponesimod are all approved for RMS – ocrelizumab, ofatumumab, and ponesimod based on an RMS study, cladribine based on an RRMS study. Data on efficacy in SPMS are only available from post hoc analyses of very small subgroups, representing only up to 15% of the total study population. For these DMTs, approval for RMS, including active SPMS, was mainly based on the assumption that the reduction in relapse rate observed in patients with RRMS can also be applied to SPMS. Based on that, the potential of these drugs to reduce relapse-independent progression remains unclear.show moreshow less

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Metadaten
Author:Antonios BayasORCiDGND, Monika ChristGND, Simon Faissner, Juliane Klehmet, Refik Pul, Thomas Skripuletz, Sven G. Meuth
URN:urn:nbn:de:bvb:384-opus4-1034216
Frontdoor URLhttps://opus.bibliothek.uni-augsburg.de/opus4/103421
ISSN:1756-2864OPAC
Parent Title (English):Therapeutic Advances in Neurological Disorders
Publisher:SAGE Publications
Place of publication:London
Type:Article
Language:English
Year of first Publication:2023
Publishing Institution:Universität Augsburg
Release Date:2023/04/04
Tag:Neurology (clinical); Neurology; Pharmacology
Volume:16
First Page:1
Last Page:21
DOI:https://doi.org/10.1177/17562864221146836
Institutes:Medizinische Fakultät
Medizinische Fakultät / Universitätsklinikum
Medizinische Fakultät / Lehrstuhl für Neurologie
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Licence (German):CC-BY 4.0: Creative Commons: Namensnennung (mit Print on Demand)