The use of immunomodulators in early rheumatoid arthritis

Immunomodulators represent a unique class of drugs that are not biologics, usually are isolated from nature, and have relatively specific noncytotoxic effects on the immune system. Although most slow-acting antirheumatic drugs (SAARDs) have effects on the immune system, these effects usually are not specific, often are cytotoxic, are not associated with specific cellular binding proteins, and their effect on immunity is difficult to correlate with their clinical effects. Most immunomodulators primarily affect T cells; because of their apparent role in rheumatoid arthritis (RA), studies of these agents are appropriate. Cyclosporine, the most widely tested of the immunomodulators, has shown significant efficacy in established RA in studies worldwide. However, only one study using cyclosporine has been performed in relatively early RA, in which the most positive effects might be expected. FK506 and rapamycin, agents similar to cyclosporine, are being tested in human transplantation; the only arthritis studies have been performed in animals. Tilomisole, imuthiol, and mycophenolate mofetil have been studied in limited RA trials, with positive effects. However, no trials have been conducted in early RA. Although promising, this class of drugs will require more studies to establish their efficacy and safety, especially in early RA.