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October 2004

Leflunomide in Psoriasis and Psoriatic Arthritis: A Preliminary Study

Arch Dermatol. 2004;140(10):1288-1289. doi:10.1001/archderm.140.10.1288

Psoriasis and its associated arthritis is an immunologic disease that is characterized by chronic inflammatory dermatosis and a seronegative arthropathy that resembles rheumatoid arthritis.1,2 Disease-modifying antirheumatic drugs, such as methotrexate, cyclosporine, and sulfasalazine, are variably effective in treating both rheumatoid and psoriatic arthritis (PA).2 Recently, leflunomide, a newer disease-modifying antirheumatic drug that has shown promising results in rheumatoid arthritis, has been used in patients with PA, with some benefit.1-3 Its active metabolite, teriflunomide (A77-1726), inhibits de novo pyrimidine synthesis through selective inhibition of a dihydro-orotase dehydrogenase.1 Actively proliferating cells, such as activated T and B lymphocytes, which require increased pyrimidine pools, undergo cell cycle arrest and inhibition of clonal expansion in the presence of leflunomide. The anti-inflammatory and immunomodulatory effects of leflunomide in PA and psoriasis may also be due to inhibition of nuclear factor κB–dependent gene transcription, tumor necrosis factor–induced activation of nuclear factor κB, and expression of cell adhesion molecules and protein kinases.3 We studied the efficacy of leflunomide in the treatment of patients with psoriasis with or without associated PA.