T-cell-activation inhibitors in rheumatoid arthritis.

As rheumatoid arthritis (RA) is a chronic inflammatory disabling disease and a cure is not available, optimisation of therapeutic strategies is mandatory. Within recent years many new details of the inflammatory cascade(s) have been elaborated, leading to new therapeutic options such as neutralisation of tumour necrosis factor-alpha (TNFalpha). T-cell inhibition is another new approach to the treatment of RA. However, it is important to note two points: first, the role of T lymphocytes in the initiation and/or perpetuation of RA is still debated controversially. Second, there are few truly T-cell-specific agents that have proven to be effective and are established in the treatment of inflammatory disorders. Leflunomide may be considered one such agent; another in development is the fusion protein CTLA4-Ig. From a clinical perspective, studies demonstrating efficacy of these agents might represent the strongest support for a role of T cells in RA. In addition to leflunomide and CTLA4-Ig, therapeutic agents with activity against T cells, including anti-CD4 antibodies, cyclosporin, tacrolimus and T-cell receptor (TCR)-Vbeta-chain vaccination strategies, have been studied in patients with RA. Combination therapies including any of these T-cell-activation inhibitors with non-T-cell-specific agents such as methotrexate, antimalarials or anti-TNFalpha biologicals may prove the most effective strategies in controlling this complex disease.