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search has been conducted and European public assessment reports of DMTs approved for RMS have been screened for unpublished data specific to SPMS.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

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© The Author(s), 2023.

Déclaration de conflit d'intérêts

The authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: AB: personal compensation from Merck Serono, Biogen, Novartis, TEVA, Roche, Sanofi/Genzyme, Celgene/Bristol Myers Squibb, Janssen, Sandoz/HEXAL; grants for congress travel and participation from Biogen, TEVA, Novartis, Sanofi/Genzyme, Merck Serono, Celgene, Janssen. MC declares that there is no conflict of interest. SF: speaker’s and/or scientific board honoraria and/or travel grants from Biogen, Bristol Myers Squibb, Celgene, Janssen, Merck, Novartis, and Roche. His research is funded by Ruhr-University Bochum, Deutsche Multiple Sklerose Gesellschaft, Stiftung für therapeutische Forschung, Lead Discovery Center GmbH, and Novartis. JK: personal compensation from Merck Serono, Biogen, Novartis, TEVA, Roche, Sanofi/Genzyme, Celgene/Bristol Myers Squibb, and Janssen. RP: honoraria for lectures and travel grants from Alexion, Bayer Healthcare, Biogen, Bristol Myers Squibb/Celgene, Horizon, Janssen-Cilag, MedDay Pharmaceuticals, Merck, Novartis, Roche, Sanofi Genzyme, Sanofi-Aventis, and Teva. He received research funding from HERZ Burgdorf, Merck, and Novartis. TS: honoraria for lectures and travel grants from Alexion, Alnylam Pharmaceuticals, Bayer Vital, Biogen, Celgene, Centogene, CSL Behring, Euroimmun, Janssen, Merck Serono, Novartis, Pfizer, Roche, Sanofi, Siemens, Sobi, and Teva. His research is funded by Alnylam Pharmaceuticals, Bristol Myers Squibb Foundation for Immuno-Oncology, Claudia von Schilling Foundation, CSL Behring, Else Kröner Fresenius Foundation, Hannover Biomedical Research School (HBRS), Internal funding of the MHH (HilF), Novartis, Sanofi Genzyme, VHF Stiftung. SGM: Honoraria for lecturing and travel expenses for attending meetings from Almirall, Amicus Therapeutics Germany, Bayer Health Care, Biogen, Bristol Myers Squibb/Celgene, Diamed, Genzyme, MedDay Pharmaceuticals, Merck Serono, Novartis, Novo Nordisk, Ono Pharma, Roche, Sanofi-Aventis, Chugai Pharma, QuintilesIMS, and Teva. His research is funded by the German Ministry for Education and Research, Bundesinstitut für Risikobewertung, Deutsche Forschungsgemeinschaft, Else Kröner Fresenius Foundation, Gemeinsamer Bundesausschuss, German Academic Exchange Service, Hertie Foundation, Interdisciplinary Center for Clinical Research Muenster, German Foundation Neurology, and Alexion, Almirall, Amicus Therapeutics Germany, Biogen, Diamed, Fresenius Medical Care, Genzyme, HERZ Burgdorf, Merck Serono, Novartis, Ono Pharma, Roche, and Teva.