Treating primary-progressive multiple sclerosis: potential of ocrelizumab and review of B-cell therapies

Abstract

Multiple sclerosis (MS) therapy has evolved rapidly with an increased availability of several immunomodulating therapies over the past two decades. Disease-modifying therapies have proven to be effective in treating relapse-remitting MS (RRMS). However, clinical trials involving some of the same agents for secondary-progressive and primary-progressive MS (SPMS and PPMS) have been largely negative. The pathogenesis of progressive MS remains unclear, but B-cells may play a significant role in chronic compartmentalized inflammation, likely contributing to disease progression. Biologics targeted at B-cells, such as rituximab, are effective in treating RRMS. Ocrelizumab is a humanized monoclonal antibody to CD20(+) B-cells that has shown positive results in PPMS with a significant reduction in disease progression. This review aims to discuss in detail the involvement of B-cells in MS pathogenesis, current progress of currently available and investigational biologics, with focus on ocrelizumab, and future prospects for B-cell therapy in PPMS.