Leflunomide in the treatment of rheumatoid arthritis and other autoimmune disorders

Abstract Leflunomide (Arava) is an isoxazole derivative approved by the US Food and Drug Administration (FDA) for the treatment of rheumatoid arthritis (RA). Its mechanism of action is based on the inhibition of dihydro‐orotate dehydrogenase, an enzyme that controls the pathway for denovo synthesis of uridine ribose monophosphate (rUMP) in activated T‐cells. Leflunomide is structurally unrelated to other known immunomodulatory drugs in clinical use. Data have demonstrated benefit in control of clinical symptoms and quality of life in RA and prevention of radiologic progression after 24 months of treatment. Further, studies suggest a role for the combination of methotrexate plus leflunomide in the treatment of some patients with refractory RA. Recent studies have also indicated efficacy in psoriatic arthritis, other autoimmune disorders and in prevention of allograft rejection. A recent important issue is reports of potentially serious liver toxicity and guidelines for monitoring toxicity.