Leflunomide (HWA486) is a disease-modifying antirheumatic drug (DMARD) used to treat rheumatoid and psoriatic arthritis. Its active metabolite, teriflunomide, inhibits dihydroorotate dehydrogenase (DHODH), suppressing pyrimidine synthesis in proliferating lymphocytes. This mechanism is validated in both in vitro cellular assays and in vivo animal models of autoimmune disease.