Use of rituximab in multiple sclerosis: current progress and future perspectives.

In recent years, new insights into the immunological pathways in multiple sclerosis (MS) have been detected. This increasing knowledge has led to more distinct treatment options in modifying the disease course of MS. In 2006, natalizumab, an alpha4-integrin monoclonal antibody, introduced a new era of MS treatment. Another promising drug is the monoclonal CD20-antibody rituximab, which depletes CD20(+) cells, pre-B cells and mature B cells. Rituximab is approved for the treatment of a number of autoimmune diseases other than MS, such as rheumatoid arthritis and non-Hodgkin's lymphoma. Early-phase trials in the autoimmune-driven disorders Sjögren's syndrome, vasculitis and thrombocytopenic purpura confirmed the use of rituximab in B-cell-mediated diseases. Another autoimmune disease affecting the CNS is neuromyelitis optica (NMO). NMO is characterized by having some similarities with MS and several studies demonstrated successful therapy of NMO using rituximab. In addition, numerous case reports in MS patients showed a stabilization of the course with a reduction of the relapse rate and MRI pathologies in MS patients. To date, one Phase II clinical trial in MS patients confirmed the results from these case reports. In this article, we will focus on the role of B cells in MS and the immunomodulatory pathways of rituximab. Recent data from experimental and clinical trials, as well as safety aspects, are discussed. A future perspective is given regarding the possible role of rituximab, as well as possible other candidates for treating MS.