Monoclonal antibody therapy in rheumatoid arthritis

Monoclonal antibodies bind to their targets with high specificity andtherefore have excellent potential as therapeutic agents. Biotechnologicaladvances have allowed the production of large quantities of engineeredmonoclonal antibodies for therapeutic use. Recent research in rheumatoidarthritis has identified important mediators of synovitis. Monoclonalantibodies targeting these have been tested in clinical trials over thelast decade. Anti-cytokine therapies, in particular anti-tumour necrosisfactor alpha monoclonal antibodies, suppressed inflammation and producedrapid symptomatic improvement. Anti-lymphocyte monoclonal antibodiesproduced long- lasting disease suppression in animal models of rheumatoidarthritis. The use of depleting anti-lymphocyte monoclonal antibodies inrheumatoid arthritis had been disappointing as they did not penetrate thesynovial joint in sufficient quantity to suppress disease without producingsevere and protracted peripheral blood lymphopenia. Consequently, their usein rheumatoid arthritis had been abandoned. In contrast, clinical trials ofnon-depleting anti-CD4 monoclonal antibodies in rheumatoid arthritis showedthat they could suppress synovitis. However, it remains unclear whetherthey could lead to prolonged disease improvement.