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  • Title: The use of leflunomide in the treatment of rheumatoid arthritis: an experimental and clinical review.
    Author: Schattenkirchner M.
    Journal: Immunopharmacology; 2000 May; 47(2-3):291-8. PubMed ID: 10878295.
    Abstract:
    Leflunomide, the newest disease-modifying antirheumatic drug (DMARD) for the treatment of rheumatoid arthritis (RA), acts by inhibiting dihydroorotate dehydrogenase, the rate-limiting enzyme in the pathway for pyrimidine production. The drug thus limits T-cell proliferation, a process thought to be a key step in the pathogenesis of RA. In placebo-controlled trials, leflunomide was superior to placebo and comparable to sulfasalazine and methotrexate for improving the signs and symptoms of RA; and superior to placebo, sulfasalazine, and methotrexate for improving health-related quality of life. In the same trials, leflunomide was also superior to methotrexate and comparable to sulfasalazine for slowing radiographically assessed progression of RA. When used in combination therapy in an open-label trial, leflunomide resulted in improvement for over half of a group of RA patients who had failed to respond to methotrexate alone. The most common adverse events associated with leflunomide treatment were gastrointestinal symptoms, allergic reactions, alopecia, and elevated liver enzyme levels. Adverse events were generally mild to moderate in severity and resolved without sequelae. Clinical trial results indicate that leflunomide is an efficacious and safe addition to the roster of therapeutic agents used to treat RA.
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