New therapeutic targets for rheumatoid arthritis

New insights into the pathogenesis of rheumatoid arthritis (RA) and consequently new targets of therapy are covered in a broad overview fashion. Short‐term significant beneficial effect on RA disease activity has been established in a small but rapidly growing number of double‐blind placebo‐controlled trials now including recombinant human IL‐1 receptor antagonist, chimeric (mouse/human) monoclonal antibodies (mAb) against TNFa (cA2), humanised (human/mouse) anti‐TNFa mAb (CDP571) and recombinant human TNF‐receptor‐Fc fusion protein (TNFR : Fc). Placebo‐controlled trials of anti‐T cells agents such as chimeric anti‐CD4 mAb (cM‐T412) and anti‐CD5 immunoconjugate, did not demonstrate clinical benefit. A placebo‐controlled study of the anti‐T cell derived cytokine IL‐2 (DAB486IL‐2) showed only modes clinical improvement. Other anti‐T cell approaches such as autologous T cell vaccination and induction of tolerance by oral type II collagen have been unsuccessful. The one controlled trial with an anti‐inflammatory cytokine, recombinant human IFN‐g, showed modest clinical benefits. Controlled trials with IL‐4 and IL‐10 and with anti‐adhesion molecules are awaited.