Management of Rheumatoid Arthritis: Defining the Role of Leflunomide
Christopher I. Carswell
Caroline M. Perry
Rheumatoid arthritis is a progressive, disabling disease which can lead to long-term deformity and disability. Leflunomide is a disease-modifying antirheumatic drug (DMARD) approved to reduce signs and symptoms, inhibit structural damage and improve physical function in adults with active rheumatoid arthritis. In clinical trials in patients with active rheumatoid arthritis, leflunomide had a more rapid onset of action than methotrexate, sulfasalazine and placebo. In trials of 24 months' duration, leflunomide was more effective than sulfasalazine and placebo and at least as effective as methotrexate in reducing rheumatoid arthritis disease activity (assessed using the American College of Rheumatology [ACR] criteria). In addition, leflunomide was as effective as sulfasalazine or methotrexate in decreasing the rate of radiological progression over 24 months. Over 12 months leflunomide was more effective than methotrexate and placebo in reducing the rate of structural damage. Data from a nonblind extension study suggests that the efficacy of leflunomide may be maintained when administered for periods up to 5 years. Leflunomide was significantly more effective than methotrexate, sulfasalazine and placebo in improving physical function measures among patients with active rheumatoid arthritis, and improved physical function was maintained after 2 years of treatment. Few well designed pharmacoeconomic analyses of leflunomide treatment in patients with rheumatoid arthritis exist. Economic studies to date show leflunomide to be either less cost effective or cost neutral compared to methotrexate. In addition, leflunomide has been shown to be a cost effective option compared with etanercept, infliximab and infliximab plus methotrexate. Leflunomide was generally well tolerated in clinical trials. Common adverse events associated with leflunomide treatment include diarrhea, respiratory infections, nausea and headache. Hematological and hepatotoxic adverse events are a concern, particularly in a setting of multiple risk factors such as concomitant hepatotoxins. Liver function monitoring should be adhered to in all patients receiving leflunomide and ACR guidelines should be followed in those receiving concomitant methotrexate. In conclusion, leflunomide is a DMARD which produces a rapid and sustained reduction in disease activity in patients with active rheumatoid arthritis. Leflunomide has a more rapid onset of action than sulfasalazine or methotrexate. Leflunomide is at least as effective as methotrexate and more effective than sulfasalazine in reducing disease activity after 24 months' treatment. In addition, leflunomide is more effective than both of these agents in improving physical function and health-related quality of life. Thus it is predicted that leflunomide therapy may improve the long-term outcome of patients with rheumatoid arthritis and reduce the substantial burden imposed by the disease for patient, healthcare provider and payers. Consequently, leflunomide should be considered as an important treatment option for those patients with active rheumatoid arthritis including those intolerant to methotrexate.
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