Treatment of rheumatoid arthritis with rituximab: an update and possible indications.

Based on new biologic and clinical insights, the number of drugs blocking different biologic targets in rheumatoid arthritis (RA) [e.g., tumor necrosis factor alpha (TNFalpha), CTLA4, interleukin (IL)-1, IL-6, IL-15, IL-18, B lymphocyte stimulator (BLyS), CD20] has increased considerably over the last decade. Rituximab, a chimeric monoclonal antibody that was developed for the treatment of B-cell lymphomas, has been used in different autoimmune diseases where B-cells are thought to play a pivotal role. However, blinded randomised controlled trials have been completed only for RA so far, indicating the clear efficacy of B-cell blockade in RA and highlighting the pathogenetic B-cell in rheumatoid synovitis. The use of rituximab in RA is herein updated, from early preliminary studies to more recent presentations in International Conferences. Key clinical and biologic issues are discussed, i.e., efficacy and safety of rituximab, role of concomitant therapies, use in the long term and retreatment strategies, differences with anti-TNFalpha therapy. The possible indications in RA are finally discussed, also on the ground of personal experience with rituximab in RA and other rheumatic diseases associated with B-cell lymphoproliferation. Further clinical research should go hand in hand with laboratory research, and tissue studies are now needed.