The use of leflunomide in the treatment of rheumatoid arthritis: an experimental and clinical review

Leflunomide, the newest disease-modifying antirheumatic drug (DMARD) for th e treatment of rheumatoid arthritis (RA), acts by inhibiting dihydroorotate dehydrogenase, the rate-limiting enzyme in the pathway for pyrimidine prod uction. The drug thus limits T-cell proliferation, a process thought to be a key step in the pathogenesis of RA. In placebo-controlled trials, lefluno mide was superior to placebo and comparable to sulfasalazine and methotrexa te for improving the signs and symptoms of RA; and superior to placebo, sul fasalazine, and methotrexate for improving health-related quality of life. In the same trials, leflunomide was also superior to methotrexate and compa rable to sulfasalazine for slowing radiographically assessed progression of RA. When used in combination therapy in an open-label trial, leflunomide r esulted in improvement for over half of a group of RA patients who had fail ed to respond to methotrexate alone. The most common adverse events associa ted with leflunomide treatment were gastrointestinal symptoms, allergic rea ctions, alopecia, and elevated liver enzyme levels. Adverse events were gen erally mild to moderate in severity and resolved without sequelae. Clinical trial results indicate that leflunomide is an efficacious and safe additio n to the roster of therapeutic agents used to treat RA. (C) 2000 Elsevier S cience B.V. All rights reserved.