New and future drug therapies for rheumatoid arthritis.

Several new drugs have recently been introduced for the treatment of rheumatoid arthritis (RA). These include the cyclooxygenase-2 inhibitor, celecoxib, the anti-tumour necrosis factor agents, etanercept and infliximab, and the new disease-modifying anti-rheumatic drug (DMARD), leflunomide. In clinical trials, celecoxib has been shown to be effective for palliation of the signs and symptoms of RA and to have fewer gastrointestinal side-effects than conventional non-steroidal anti-inflammatory drugs. Etanercept and infliximab are indicated for reduction of the signs and symptoms of RA in patients who have failed to respond adequately to previous DMARDs. The clinical success rate in etanercept-treated patients is significantly better than in placebo-treated patients for up to 18 months. Leflunomide is a DMARD with a novel mechanism of action that has been approved as a first-line treatment for RA. Treatment with leflunomide results in significantly greater improvement of the signs and symptoms of RA than placebo for up to 2 yr and slows radiographically assessed disease progression. Agents are currently in development that will be targeted against components of the immune activation and co-stimulatory pathways. These include antibodies directed against the interleukin-2 receptor and blockers of the CD28 and CD40 co-stimulatory pathways. Continuing research into the pathogenesis of RA will undoubtedly identify even more effective therapeutic approaches for the management of this disease in the future.