• Tuberculosis and Respiratory Diseases
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• v.66 no.6
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• pp.477-481
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• 2009

Leflunomide, a disease-modifying antirheumatic drug (DMARD) for the treatment of rheumatoid arthritis has been available in Korea since 2003. Leflunomide-associated interstitial pneumonitis has been appearing recently. A 25-year-old woman with a 12-month history of seronegative rheumatoid arthritis (RA) presented with acute respiratory insufficiency. She developed fever, dyspnea, and non-productive cough. Her medication history included methotrexate (15 mg/week. commencing 1 year prior) and leflunomide (20 mg/day, no loading dose, commencing 4 months prior). She was diagnosed with leflunomide-associated interstitial pneumonitis based on history, physical examination, laboratory and radiologic findings. She recovered quickly after leflunomide was withdrawn and steroids and cholestyramine were initiated quickly. We report a case of leflunomide-associated interstitial pneumonitis treated successfully with intravenous high-dose steroid and cholestyramine.

• Tuberculosis and Respiratory Diseases
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• v.58 no.1
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• pp.83-88
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• 2005

Leflunomide is a new disease modifying anti rheumatic drug (DMARD) for the treatment of active rheumatoid arthritis. Its mechanism of action differs from other DMARDs in that it inhibits the de novo pyrimidine synthesis by inhibiting dihydroorotate dehydrogenase and therefore prevents the proliferation of activated lymphocytes. As it has been prescribed worldwide, there is a great deal of much concerns regarding its potential adverse effects. Because leflunomide has an active metabolite with a long elimination half-life of approximately 2 weeks, serious adverse reactions may occur even after the leflunomide treatment has been stopped. The profile of serious reactions includes liver dysfunction, hematological disorders, severe skin reactions and respiratory dysfunction. Respiratory dysfunctions with leflunomide therapy are very rare and its incidence is lower than that of methotrexate therapy. However, there are reports in Japan showing that 5 patients died of interstitial pneumonitis and another 11 patients developed serious lung complications associated with leflunomide. This suggests the possibility of fatal respiratory toxicity of leflunomide. There are no reports of interstitial pneumonitis associated with leflunomide in Korea. We report a case of a 62-year old woman who developed interstitial pneumonitis, which might have been induced by leflunomide during the treatment of rheumatoid arthritis.

• Biomedical Science Letters
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• v.15 no.1
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• pp.61-66
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• 2009

Leflunomide is an immunomodulatory agent used for the treatment of rheumatoid arthritis (RA). Leflunomide known as a regulator of iNOS synthesis which largely decreases NO production in diverse cell type. However, the effect of leflunomide on chondrocyte is still poorly understood. In our previous studies, we have shown that direct production of Nitric oxide (NO) by treating chondrocytes with NO donor, sodium nitroprusside (SNP), causes apoptosis via p38 mitogen-activated protein kinase in association with elevation of p53 protein level, caspase-3 activation. In this study, we characterized the molecular mechanism by which A77 1726 inhibit apoptosis. We found that A77 1726 inhibit NO-induced apoptosis as determined by MTT (Thiazolyl Blue Tetrazolium Bromide) assay and DNA fragmentation. The inhibition of apoptosis by A77 1726 was accompanied by increased PI-3 kinase and AKT activities. So, inhibition of phosphatidylinositol (PI)-3kinase with LY294002 rescued apoptosis. Triciribine, the specific inhibitor of AKT, also abolished anti-apoptotic effect. Our results indicate that A77 1726, the active metabolite of leflunomide, mediates NO-induced apoptosis in chondrocytes by modulating up-regulation of PI-3 kinase and AKT.

• Archives of Pharmacal Research
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• v.26 no.3
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• pp.197-201
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• 2003

Novel $\beta$-hydroxy propenamides as analogues of the active metabolite of leflunomide (A 771726) were synthesized and evaluated for their inhibitory activity on dihydroorotate dehydrogenase (DHODH) in an investigation into their immunosuppressive activity. Compounds 2a, 3a, and 3h were approximately 4-40 times more potent than leflunomide in their activity while they were-less active than A 771726.

• YAKHAK HOEJI
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• v.50 no.2
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• pp.70-77
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• 2006

A cost effective analysis was performed for comparing leflunomide+methotrexate, etanercept monotherapy and etanercept+methotrexate for 6 months. For the patients with methotrexate-resistant RA, ACR20 data were extracted from the published clinical trials searched from Pubmed. The direct medical cost was estimated based on ACR guideline and Korean National Health Insurance reimbursement. Combination therapy of etanercept+methotrexate was found to be more cost-effective than etanercept monotherapy, which meant it was a better therapeutic strategy for methotrexate- resistant RA.

• Tuberculosis and Respiratory Diseases
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• v.77 no.6
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• pp.266-270
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• 2014

Recently, the incidence of pulmonary cryptococcosis is gradually increasing in rheumatoid arthritis (RA) patients. Pulmonary rheumatoid nodules (PRN) are rare manifestations of RA. Eighteen months ago, a 65-year old woman was admitted to hospital due to multiple nodules ( $2.5{\times}2.1{\times}2cm$) with cavitations in the right lower lobe. She was diagnosed with RA three year ago. She had been taking methotrexate, leflunomide, and triamcinolone. A video-assisted thoracoscopic surgery biopsy was performed and PRN was diagnosed. However, a newly growing huge opacity with cavitation was detected in the same site. Pulmonary cryptococcal infection was diagnosed through a transthoracic computed tomograpy guided needle biopsy. Cryptococcus antigen was detected in serum but not in cerebrospinal fluid. The patient was treated with oral fluconazole which resulted clinical improvement and regression of the nodule on a series of radiography. Herein, we report the case of pulmonary cryptococcosis occurring in the same location as that of the PRN.

• Proceedings of the Korean Society of Veterinary Clinics Conference
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• 2006.11a
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• pp.134-134
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• 2006