Multiple Sclerosis: Unprecedented Progress But Significant Challenges Ahead

Abstract

One of the most challenging aspects of our role as guest editors for this special issue of Neurotherapeutics was deciding on the topics for review. Progress in the field of multiple sclerosis (MS) research has been substantial over the last several years. Whereas it may once have been possible to cover the entire field of MS in a single issue, that is certainly not the case today. Thus, rather than trying to be comprehensive, we selected topics that we felt would be the most high impact for our readers, allowing them to treat, educate, and advise patients with MS through the varied and complicated circumstances that they often present in the clinic. Additionally, despite much progress, several significant challenges in MS management remain, which we have attempted to highlight.The issue focuses on 4 main themes. First, several disease modifying therapies (DMTs) with complex safety profiles recently received regulatory approval, and we felt it important to cover these agents. Second, despite the rapid proliferation of DMTs over the last 10 years, situations sometimes arise in which no available treatment option is sufficiently potent for a patient. Further, unmet needs with respect to remyelination and neuroprotection, especially in progressive MS, are quite urgent. Thus, we wanted to acquaint our readers with the current pipeline of treatments and procedures that will hopefully be routinely available for patients with MS in the near future. Third, MS clinical trials are a constantly evolving subject, especially with respect to outcomes, which prompted us to review some of the newest concepts in clinical trial design. Finally, with so many DMTs available, the decision of which to use and when requires greater sophistication than ever before. Not only is the choice a delicate balance of safety, efficacy, and cost, but there are also special populations to consider, such as pregnant women and children. Therefore, we conclude with a series of articles addressing important treatment considerations.With respect to currently available therapies, ocrelizumab has generated significant excitement not only due to its potent efficacy in relapsing-remitting MS, but also as the first agent to receive approval for the treatment of primary progressive MS. Gelfand et al.[1] provide a comprehensive review of Bcell biology and its relationship to MS, as well as covering ocrelizumab, rituximab, and ofatumumab. Daclizumab is a recently approved agent that requires intensive safety monitoring, especially with respect to hepatotoxicity and cutaneous events. Baldassari and Rose [2] provide a thoughtful analysis of its place in the DMT landscape. Finally, Chaudhry et al. [3] review fingolimod and present a bridge into the pipeline section with a discussion of second-generation sphingosine-1-phosphate receptor modulators with greater receptor subtype specificity.Pipeline treatments include cladribine, which was rejected by the Food and Drug Administration and the European Medicines Agency several years ago but recently received approval ...