New therapeutic targets for rheumatoid arthritis

New insights into the pathogenesis of rheumatoid arthritis (RA) and consequ ently new targets of therapy are covered in a broad overview fashion. Short -term significant beneficial effect on RA disease activity has been establi shed in a small but rapidly growing number of double-blind placebo-controll ed trials now including recombinant human IL-1 receptor antagonist, chimeri c (mouse/human) monoclonal antibodies (mAb) against TNF alpha (cA2), humani sed (human/mouse) anti-TNF alpha mAb (CDP571) and recombinant human TNF-rec eptor-Fc fusion protein (TNFR : Fc). Placebo-controlled trials of anti-T ce lls agents such as chimeric anti-CD4 mAb (cM-T412) and anti-CD5 immunoconju gate, did not demonstrate clinical benefit. A placebo-controlled study of t he anti-T cell derived cytokine IL-2 (DAB(486)IL-2) showed only modes clini cal improvement. Other anti-T cell approaches such as autologous T cell vac cination and induction of tolerance by oral type II collagen have been unsu ccessful. The one controlled trial with an anti-inflammatory cytokine, reco mbinant human IFN-gamma, showed modest clinical benefits. Controlled trials with IL-4 and IL-10 and with anti-adhesion molecules are awaited.