New and future drug therapies for rheumatoid arthritis

Several new drugs have recently been introduced for the treatment of rheuma toid arthritis (RA). These include the cyclooxygenase-2 inhibitor, celecoxi b, the anti-tumour necrosis factor agents, etanercept and infliximab, and t he new disease-modifying anti-rheumatic drug (DMARD), leflunomide. In clini cal trials, celecoxib has been shown to be effective for palliation of the signs and symptoms of RA and to have fewer gastrointestinal side-effects th an conventional non-steroidal anti-inflammatory drugs. Etanercept and infli ximab are indicated for reduction of the signs and symptoms of RA in patien ts who have failed to respond adequately to previous DMARDs. The clinical s uccess 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 improv ement of the signs and symptoms of RA than placebo for up to 2 yr and slows radiographically assessed disease progression. Agents are currently in dev elopment 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 pat hways. Continuing research into the pathogenesis of RA will undoubtedly ide ntify even more effective therapeutic approaches for the management of this disease in the future.