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

Antonios Bayas; Monika Christ; Simon Faissner; Juliane Klehmet; Refik Pul; Thomas Skripuletz; Sven G Meuth

doi:10.1177/17562864221146836

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

Ther Adv Neurol Disord. 2023 Jan 24:16:17562864221146836. doi: 10.1177/17562864221146836. eCollection 2023.

Authors

Antonios Bayas¹, Monika Christ¹, Simon Faissner², Juliane Klehmet³, Refik Pul⁴, Thomas Skripuletz⁵, Sven G Meuth⁶

Affiliations

¹ Department of Neurology, Faculty of Medicine, University of Augsburg, Augsburg, Germany.
² Department of Neurology, St. Josef-Hospital, Ruhr-University Bochum, Bochum, Germany.
³ Department of Neurology, Jüdisches Krankenhaus Berlin, Berlin, Germany.
⁴ Department of Neurology and Center for Translational and Behavioral Neurosciences (C-TNBS), University Medicine Essen, Essen, Germany.
⁵ Department of Neurology, Hannover Medical School, Hannover, Germany.
⁶ Department of Neurology, Medical Faculty, Heinrich Heine University Düsseldorf, Moorenstr. 5, Düsseldorf 40225, Nordrhein-Westfalen, Germany.

Abstract

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search has been conducted and European public assessment reports of DMTs approved for RMS have been screened for unpublished data specific to SPMS.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.

Keywords: disease modifying treatment; multiple sclerosis; relapsing-remitting multiple sclerosis; review; secondary progressive.

Publication types

Review