Rheumatoid_Arthiritis

Rheumatoid arthritis (RA) is a systemic autoimmune disease that causes persistent chronic inflammation in the synovial membrane of affected joints involving peripheral joints in a symmetric distribution. Synovial inflammation leads to cartilage damage, bone erosion and subsequent changes in joint integrity. Around the globe almost 0.5-1% population is affected. A three times higher prevalence has been observed in women as compared to men. The disease can begin at any age, but it most often starts after age 40 and before 60.A genetic predisposition is also thought upon as cases of multiple sufferers in single families are being observed. Etiology of this disease is yet a question but the understanding of the pathophysiology of RA had increased many folds over years. The complex paraphernalia of immune response comprising of activated T-cells, stimulatory monocytes , synovial fibroblasts, macrophages and B-cells all come into play. This starts a ball game of inflammatory mediators which causes the various signs and symptoms of the disease. Depending on this understanding, many novel therapies are designed. This paper discusses one such, the “Efficacy of B-cell targeted therapy with Rituximab in patients with RA.” (1) The actual function of B-cell in RA is not clear but various evidences like B-cells migration into and accumulation within rheumatoid synovium, production of auto-antibodies like rheumatoid factors which is associated with more aggressive articular disease, also that B-cells function as antigen-presenting cells and provide co-stimulatory signals needed for CD4+ T-cells clonal expansion proves its critical role in RA. So a drug which would deplete B-cells subpopulation would show beneficial effect on RA and this was evident in an open level study of Rituximab with Cyclophosphamide and corticosteroids. Rituximab is a chimeric monoclonal antibody to the B-cell specific antigen CD20. This antigen is expressed on both pre and mature B-cells but not on stem cells and plasma cells. So rituximab binds to CD20 and deplete Bcells via mechanisms including complement mediated lysis antibody dependent cytotoxicity and apoptosis. To confirm the role of B-cells in RA this randomized, multicenter, double blind controlled study was conducted and results were assessed at week 24(primary analysis) and 48(exploratory analysis).