Emerging treatments for rheumatoid arthritis.

Rheumatoid arthritis was considered for centuries to be a nuisance condition, limiting in its effects on an individual's range of motion and the source of considerable distress, but not a life-threatening disease. Recently, however, it has become apparent that patients with severe rheumatoid arthritis may have a decreased life span. Current pharmacologic therapies for patients with rheumatoid arthritis, which include nonsteroidal anti-inflammatory drugs, disease-modifying antirheumatic drugs, methotrexate, and corticosteroids, have been moderately successful in alleviating the discomforts associated with swollen, painful joints. Many practitioners have sought to improve use of these agents and slow joint destruction by challenging traditional treatment paradigms, altering the sequence in which drugs are given. Nevertheless, most standard medical approaches to treatment have had little or no impact on the course of rheumatoid disease. Innovative strategies, particularly those based on new concepts in the immunobiology of rheumatoid arthritis, are being developed to target cellular inflammatory mechanisms and actually prevent disease progression. Some agents, such as inhibitors of 5-lipoxygenase-omega-3 fatty acid and zileuton-may be most useful in treatment of milder disease manifestations such as moderate synovitis. Other agents, such as oral type II collagen, minocycline, subcutaneous interleukin-1ra, and anti-CD4 monoclonal antibodies, have produced such inconsistent results that substantial additional research will be required before any conclusions may be drawn about their value. Among the most promising agents, and the most extensively studied, are tumor necrosis factor-alpha monoclonal antibodies, immunosuppressive drugs such as cyclosporine and mycophenolate mofetil, and the novel compound tenidap, which has both cytokine-modulating and anti-inflammatory properties.