Predictive factors of response to rituximab therapy in rheumatoid arthritis: What do we know today?

Interest in the role of B cells in the pathogenesis of rheumatoid arthritis (RA) has increased over recent years. Rituximab (RTX), a chimeric monoclonal antibody specific for human CD20 targeting B lymphocytes, has been used to treat RA patients, and its efficacy has been clearly demonstrated in controlled clinical trials and open-label observational studies. However, it is still not known which sub-group(s) of patients will respond to RTX therapy or whether there are any factors predicting a response. The aim of this review is to discuss the most important predictive factors that are so far known. It is known that the clinical response to RTX therapy is associated with lower interferons (IFN-γ) and B-cell activating factor (BAFF) levels, the Fcγ receptor III (FcγRIII) genotype, and the C/G-174 polymorphism of interleukin 6 (IL-6); that an initial non-response to RTX depends on circulating pre-plasma cell numbers at baseline and incomplete depletion; that synovial B cells are decreased but not eliminated by RTX therapy, and that a good clinical response correlates with more substantial synovial B depletion; and, finally, that a good clinical response correlates with rheumatoid factor positivity, but not anti-cyclic citrullinated peptide antibody positivity.