• Olaf Hoffmann and Ralf Gold.
• NeuroCure Clinical Research Center, Charité - Universitätsmedizin Berlin, Charitéplatz 1, 10117, Berlin, Deutschland. olaf.hoffmann@charite.de.
• Nervenarzt. 2021 Oct 1; 92 (10): 1052-1060.

BackgroundMultiple sclerosis (MS) is a disease continuum from a clinically isolated syndrome through relapsing remitting MS to secondary progressive MS (SPMS). There are numerous therapeutic approaches with proven efficacy on relapse and focal inflammatory disease aspects, whereas treatment of secondary progression and associated neuropathological aspects continues to be a challenge.ObjectiveOverview of the current options for disease-modifying treatment of SPMS.Material And MethodsResults of randomized clinical trials are presented and evaluated on a substance-specific basis.ResultsRandomized SPMS trials showed inconsistent results regarding disability progression for beta interferons and negative results for natalizumab. Oral cladribine and ocrelizumab reduced disability progression in relapsing MS but have not been specifically studied in an SPMS population. Positive results for mitoxantrone are only partially applicable to current SPMS patients. For siponimod, a substance that crosses the blood-brain barrier, the EXPAND trial demonstrated a significant reduction in the risk of disability progression in typical SPMS. Subgroup analyses suggest a higher efficacy of siponimod in younger patients with active SPMS.ConclusionThere is limited evidence for the use of previously available disease-modifying treatment in SPMS. Siponimod represents a new therapeutic option for active SPMS, defined by relapses or focal inflammatory MRI activity. To establish the therapeutic indications for siponimod, early detection of relapse-independent progression as well as differentiation of active SPMS from inactive disease are of critical importance.© 2021. The Author(s).

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