Treatment of Patients with Multiple Sclerosis Transitioning Between Relapsing and Progressive Disease

Multiple sclerosis (MS) is a chronic autoimmune demyelinating and neurodegenerative disease of the central nervous system with a wide variety of clinical phenotypes. In spite of the phenotypic classification of MS patients, current data provide evidence that diffuse neuroinflammation and neurodegeneration coexist in all MS forms, the latter gaining increasing clinical relevance in progressive phases. Given that the transition phase of relapsing-remitting MS (RRMS) to secondary progressive MS (SPMS) is not well defined, and widely accepted criteria for SPMS are lacking, randomised controlled trials (RCTs) specifically designed for the transition phase have not been conducted. This review summarizes primary and secondary analyses and reports derived from phase III prospective clinical RCTs listed in PubMed of compounds authorised through the European Medicines Agency (EMA) and the US Food and Drug Administration (FDA) for the treatment of MS. The best data are available for interferon beta-1a (IFNb-1a) subcutaneous (s.c.), IFNb-1b s.c., mitoxantrone and siponimod, the latter being the most modern compound with likely the best risk-to-effect ratio. Moreover, there is a labels discrepancy for many disease-modifying treatments (DMTs) between the FDA and EMA, which have to be taken into consideration when opting for a specific DMT.