Updates on efficacy and safety outcomes of new and emerging disease modifying therapies and stem cell therapy for Multiple Sclerosis: A review

MS is a chronic autoimmune inflammatory and demyelinating disease affecting the CNS that can present with a myriad of focal and non-focal neurologic symptoms (Lassmann et al., 2007). Over recent decades, our understanding of MS from both an immunological and therapeutic perspective has expanded a great deal. Currently, MS can be classified under several different subtypes based on the clinical course of the disease, including the more classically known subtypes of relapsing remitting MS (RRMS), primary progressive MS (PPMS), secondary progressive MS (SPMS), and progressive relapsing MS (PRMS) as well as the more recently characterized radiologically isolated syndrome (RIS) and clinically isolated syndrome (CIS) (Klineova and Lublin, 2018). Of these subtypes, RRMS is a common therapeutic target as approximately 85% of patients initially present with this disease course, some of which later progress to SPMS. A much smaller population of approximately 10–15% of patients present initially with a PPMS course, with even fewer presenting with other subtypes (Faissner and Gold, 2018). Alongside the understanding of these subtypes have come advancements in treatments targeting all or even specific subtypes based on their clinical pathology. However, as we have studied MS and its clinical presentation over the years, our understanding has begun to evolve into that of MS as a continuum rather than strict categories or subtypes, and this may change characterizations in the future.

The first MS DMT ever developed was subcutaneous interferon (IFN) beta 1b, approved in 1993 by the Food and Drug Administration (FDA) for the treatment of RRMS (Bayas and Gold, 2003). Soon after this, other IFN agents and a new agent, glatiramer acetate (GA), were introduced. New therapies then began to develop rapidly over the next 30 years, including oral agents such as fingolimod, dimethyl fumarate, teriflunomide, cladribine, siponimod, ozanimod, and ponesimod, as well as the now commonly used parenteral monoclonal antibodies such as natalizumab, rituximab, alemtuzumab, ocrelizumab, and ofatumumab (TaŞKapilioĞLu, 2018).

However, despite these advances, we continue to have a strong need for continued development of treatment options for people living with MS. There are still many patients who fail to respond to current treatment regimens, and there are few options available for patients that have progressed to SPMS or have more aggressive forms of MS such as PPMS (Rotstein et al., 2015; Kappos et al., 2018; Montalban et al., 2017). This has prompted the continuous research into novel therapies with improved efficacy and safety outcomes to better treat the MS patient population.

Due to the rapid growth of the field of DMTs, it can be a challenge for clinicians to stay up to date with all of the current and up-and-coming treatment options available to their MS patients. The progress in the development of new DMT options is still occurring every day, with many new therapies currently undergoing clinical trials. In this review, we aim to provide a comprehensive overview of these emerging DMTs, their clinical trial status, results, and available safety data in the hopes that this information will better prepare clinicians for the appropriate prescribing of future treatment options.

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