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 dihydroorotate 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.

Leflunomide-Induced Acute Interstitial Pneumonia in a Patient Treated for Rheumatoid Arthritis

“…Chikura et al found that 75% of the reviewed cases had received steroids, 31% had received antimicrobial treatment, and 22% were treated with both steroids and antibiotics [12]. The elimination of leflunomide may be accelerated by cholestyramine, and this is a very promising treatment option [2,12,13]. Wong et al reported a case of successful treatment with cholestyramine in monotherapy administered orally in a dose of 8 g three times daily [14], but further convincing data on the efficacy of this drug in the treatment of leflunomide-induced lung injury are required.…”

“…Leflunomide, a DMARD introduced more than a decade ago, was reported to alleviate RA symptoms and retard radiological progression of the disease [2]. However, adverse-event moni-toring revealed an increased risk of interstitial lung disease in predisposed individuals.…”

Diagnosis and management of rheumatoid arthritis

“…Concurrent NSAID use may exacerbate this phenomenon. 18 Frequent blood pressure monitoring is often advised. Other adverse effects of leflunomide include nausea, diarrhoea and rash.…”

“…It has a half life of around 15 days. 18 Elimination is via the gastrointestinal tract and kidneys. Teriflunomide goes through extensive enterohepatic recircula tion.…”