Leflunomide - New DMARD for Rheumatoid Arthritis
Leflunomide, an isoxazole derivative, is rapidly converted to an active metabolite which inhibits lymphocyte proliferation. Like other disease-modifying anti-rheumatic drugs (DMARDs), leflunomide slows the rate of progression of joint damage in patients with rheumatoid arthritis. The drug produces a clinical response in about 40 to 65% of patients with active disease. Leflunomide appears to be at least as effective as methotrexate and more so than sulfasalazine in the longer term; as well, leflunomide may reduce functional disability more effectively and be faster acting than methotrexate or sulfasalazine.
The tolerability of leflunomide is generally similar to that of methotrexate or sulfasalazine. Hepatic function must be monitored regularly and haematological adverse events and serious skin reactions can occur rarely in patients who receive leflunomide; the drug also has the potential to be teratogenic. Therefore, all recommendations for use of the drug should be strictly observed. The long term efficacy and comparative pharmacoeconomics of leflunomide treatment are not yet known.
Rheumatoid arthritis is a progressive, debilitating disease, characterised by chronic inflammation of multiple synovial joints, that affects 0.5 to 1% of the population. The disease has an unpredictable course but in most patients active phases alternate with periods of remission. Significant pain, fatigue, loss of function and psychosocial impairment are common symptoms. Joint damage develops in 75% of patients within 2 years of the onset of symptoms. Although the disease is thought to be mediated by activated, autoimmune lymphocytes, its aetiology is unknown. As there is no cure, the goal of therapy is to achieve complete remission.
Active rheumatoid arthritis is managed primarily with pharmacotherapy. First-line therapy usually relies on nonsteroidal anti-inflammatory drugs (NSAIDs) to control joint pain and improve function. Second-line therapy is with DMARDs such as methotrexate or sulfasalazine, often in combination with NSAIDs and other anti-inflammatory agents. Anti-inflammatory agents do not alter the disease process, but DMARDs can slow or prevent damage to affected joints.
Adverse events are a major limitation in the use of all DMARDs. Among the older DMARDs, methotrexate appears to have the best efficacy/toxicity ratio, while sulfasalazine appears to be nearly as effective as methotrexate but is generally not as well tolerated. Leflunomide, a new DMARD, is effective against active rheumatoid arthritis in adults and is about as well tolerated as these 2 older drugs (see Differential features table).
Leflunomide, an isoxazole derivative, is rapidly converted to an active metabolite which inhibits lymphocyte proliferation. Like other disease-modifying anti-rheumatic drugs (DMARDs), leflunomide slows the rate of progression of joint damage in patients with rheumatoid arthritis. The drug produces a clinical response in about 40 to 65% of patients with active disease. Leflunomide appears to be at least as effective as methotrexate and more so than sulfasalazine in the longer term; as well, leflunomide may reduce functional disability more effectively and be faster acting than methotrexate or sulfasalazine.
The tolerability of leflunomide is generally similar to that of methotrexate or sulfasalazine. Hepatic function must be monitored regularly and haematological adverse events and serious skin reactions can occur rarely in patients who receive leflunomide; the drug also has the potential to be teratogenic. Therefore, all recommendations for use of the drug should be strictly observed. The long term efficacy and comparative pharmacoeconomics of leflunomide treatment are not yet known.
Rheumatoid arthritis is a progressive, debilitating disease, characterised by chronic inflammation of multiple synovial joints, that affects 0.5 to 1% of the population. The disease has an unpredictable course but in most patients active phases alternate with periods of remission. Significant pain, fatigue, loss of function and psychosocial impairment are common symptoms. Joint damage develops in 75% of patients within 2 years of the onset of symptoms. Although the disease is thought to be mediated by activated, autoimmune lymphocytes, its aetiology is unknown. As there is no cure, the goal of therapy is to achieve complete remission.
Active rheumatoid arthritis is managed primarily with pharmacotherapy. First-line therapy usually relies on nonsteroidal anti-inflammatory drugs (NSAIDs) to control joint pain and improve function. Second-line therapy is with DMARDs such as methotrexate or sulfasalazine, often in combination with NSAIDs and other anti-inflammatory agents. Anti-inflammatory agents do not alter the disease process, but DMARDs can slow or prevent damage to affected joints.
Adverse events are a major limitation in the use of all DMARDs. Among the older DMARDs, methotrexate appears to have the best efficacy/toxicity ratio, while sulfasalazine appears to be nearly as effective as methotrexate but is generally not as well tolerated. Leflunomide, a new DMARD, is effective against active rheumatoid arthritis in adults and is about as well tolerated as these 2 older drugs (see Differential features table).
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