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신장이식 후 BK 바이러스 관련 신병증에서의 Leflunomide의 임상경험
손영기 ( Young Ki Son ),오준석 ( Joon Seok Oh ),오혜주 ( Hyae Ju Oh ),신용휸 ( Yong Hun Shin ),김중경 ( Joong Kyung Kim ),정현주 ( Hyeon Joo Jeong ) 대한신장학회 2009 Kidney Research and Clinical Practice Vol.28 No.3
목적: BK 바이러스 관련 신병증 (BK virus associated nephropathy, BKVAN)은 새로운 면역억제재 도입 이후 이식신 소실의 주요한 원인중의 하나로 부각되고 있다. Leflunomide는 류마티스관절염의 치료제로 개발된 이후 강력한 면역억제작용과 시험관 시험자료에서 BK virus의 억제 작용을 동시에 지님이 알려져 있다. 이에 저자들은 신장이식환자에서 발생한 BKVAN의 치료제로서 leflunomide의 효과에 대해서 알아보고자 하였다. 방법: 신장이식 후에 BKVAN pattern B로 진단된 환자 6명을 대상으로 하였다. 모든 환자들은 진단 당시 소변 내 decoy 세포 양성소견을 보였고 혈액 내 BK 바이러스 중합연쇄반응 양성이었으며 신 조직검사상 BKVAN에 합당한 소견을 보였다. 진단과 동시에 MMF를 중단하였고 tacrolimus의 혈중최저농도를 5 ng/mL 이하로 유지하였고 steroid의 투여양은 하루 5 mg으로 조절하였다. Leflunomide는 초기 하루 100 mg을 5일간 사용하였고 유지용량으로 하루 40 mg을 투여하였다. Leflunomide의 치료기간은 6-16개월 이었다. 결과: Leflunomid투여 전 평균 혈청 크레아티닌은 2.8±0.7 mg/dL에서 경과관찰종료 시점까지의 평균 혈청 크레아티닌은 2.3±0.5 mg/dL로 비교적 안정된 상태를 보이는 경향이었고 신기능소실은 관찰되지 않았다. Leflunomide투여 전 3명의 환자에서 빈혈이 관찰되었으나 약물투여 후 악화되는 경향은 관찰되지 않았고 간기능저하, 용혈성빈혈의 발생, 간질성 폐질환등 약물용량을 조절하거나 약물중단을 일으킬만한 심각한 부작용은 없는 것으로 조사되었다. 결론: 신장이식환자에서 발생한 BKVAN의 치료에 있어서 leflunomide의 사용이 도움이 될 수 있을 것으로 생각되나 항 바이러스작용과 안정성 등에 있어서 더 많은 연구가 있어야 할 것으로 생각된다. Purpose: BK virus associated nephropathy (BKVAN) affects 1-10% of kidney transplant (KT) patients and it produces a progressive destruction of allograft. Reducing immunosuppression is the only way to save the graft, while it needs tight monitoring of the graft rejection and graft survival is poorer in advanced case. Leflunomide has immunosuppressive effect and also antiviral activity. Addition of leflunomide may improve BK virus clearance and graft survival. Methods: 6 KT patients with biopsy proven BKVAN (Histological pattern B) were treated with leflunomide and reduced immunosuppression. All patients were monitored with serial determination of viral load in blood and graft function. Results: BKVAN was diagnosed at 14 months (7-28) post transplant, at that time median serum creatinine concentration was 2.8 mg/dL (1.8-3.6). 12.5 months (6-16) later of leflunomide treatment, median serum creatinine was 2.3 mg/dL and no graft loss was found. Conclusion: Leflunomide therapy with reduced immunosuppression may be effective in the treatment for BKVAN.
류마티스 관절염 환자에서 leflunomide 복용 중 발생한 용혈성 빈혈 1예
박소연,백수영,박세우,김주형,손창남,조수경,김일,배상철 대한임상약리학회 2008 Translational and Clinical Pharmacology Vol.16 No.2
Leflunomide is a new isoxazole based disease-modifying antirheumatic drug for the treatment of rheumatoid arthritis. Leflunomide alone or combination with methotrexate has been reported to be safe as well as effective in patients with rheumatoid arthritis. Although a few cases of leflunomide-induced pancytopenia were identified, leflunomide-induced hemolytic anemia in rheumatoid arthritis has not been reported yet. We present a case of leflunomide-induced hemolytic anemia in a patient with rheumatoid arthritis. Leflunomide is a new isoxazole based disease-modifying antirheumatic drug for the treatment of rheumatoid arthritis. Leflunomide alone or combination with methotrexate has been reported to be safe as well as effective in patients with rheumatoid arthritis. Although a few cases of leflunomide-induced pancytopenia were identified, leflunomide-induced hemolytic anemia in rheumatoid arthritis has not been reported yet. We present a case of leflunomide-induced hemolytic anemia in a patient with rheumatoid arthritis.
박용범 ( Yong Beom Park ),이수곤 ( Soo Kon Lee ) 대한류마티스학회 2000 대한류마티스학회지 Vol.7 No.4
Leflunomide is a novel, isoxazol based disease-modifying anti-rheumatic drug (DMARD) for the treatment of rheumatoid arthritis (RA). Its mechanism differs from other DMARDs in that it inhibits de novo pyrimidine synthesis by inhibiting the enzyme dihydroorotate dehydrogenase (DHODH). It is a pro-drug and undergoes rapid conversion to its active form in vivo, A77-1726. A77-1726 inhibits the mitochondrial enzyme DHODH, which plays a key role in the denovo synthesis of pyrimidine ribonucleotide uridine monophosphate (rUMP). Leflunomide prevents clonal expansion of activated lymphocytes by interfering with the cell cycle progression due to inadequate production of rUMP and utilizing mechanisms involving p53. The relative lack of toxicity of A77-1726 on non-lymphoid cells may be due to the ability of these cells to fulfill their ribonucleotide requirements by use of salvage pyrimidine pathway, which makes them less dependent on de novo synthesis. Several phase II clinical trials of patients with RA revealed that leflunomide was effective and well tolerated. Large-scale phase III clinical trials have shown that leflunomide (20mg/day) provided a statistically significant clinical benefit and prevention of radiographic progression in comparison to placebo. The clinical benefits of leflunomide were similar to or greater than methotrexate and sulfasalazine. Now, many multi-national studies are in progress and planning, including combination therapy with other DMARD. In future, those studies will provide us more information about the effectiveness and potential adverse effect of leflunomide.
Leflunomide로 치료중인 류마티스 관절염 환자에서 발생한 간질성 폐렴
신아영 ( Ah Young Shin ),김승수 ( Seung Soo Kim ),김경희 ( Kyung Hee Kim ),주일남 ( Il Nam Ju ),고혁재 ( Hyeok Jae Ko ) 대한결핵 및 호흡기학회 2009 Tuberculosis and Respiratory Diseases Vol.66 No.6
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.
Case Report : Leflunomide-induced Toxic Epidermal Necrolysis in a Patient with Rheumatoid Arthritis
( Ji Hye Je ),( Hyun Jung Lee ),( Young Ju Na ),( Ji Hye Seo ),( Young Ho Seo ),( Jae Hoon Kim ),( Sung Jae Choi ),( Young Ho Lee ),( Jong Dae Ji ),( Gwan Gyu Song ) 대한류마티스학회 2014 대한류마티스학회지 Vol.21 No.6
Leflunomide was licensed for the treatment of rheumatoid arthritis in 1998 and has been available in Korea since 2003. Allergic cutaneous reactions (rash, purpura) are common (<10%) side effects of leflunomide, but severe cases such as Stevens-Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN) are rarely reported. There has not been a report of SJS or TEN induced by leflunomide in Korea. Here we report a case of leflunomide-induced TEN in a patient with rheumatoid arthritis. Leflunomide was discontinued, and the TEN was treated with methylprednisolone, cholestyramine and immunoglobulin. The skin lesion eventually resolved over four weeks with residual post-inflammatory hyperpigmentation.
류마티스관절염 환자에서 레플루노마이드와 메토트렉세이트 병합요법의 간독성 조사
장재호 ( Je Ho Chang ),정은숙 ( Eun Sook Jung ),이주현 ( Ju Hyun Lee ),윤보영 ( Bo Young Yoon ),이찬희 ( Chan Hee Lee ),이윤우 ( Yun Woo Lee ) 대한류마티스학회 2009 대한류마티스학회지 Vol.16 No.1
Objective: Leflunomide is the newest disease-modifying anti-rheumatic drug (DMARD) that is known to have an equivalent clinical efficacy and tolerability to methotrexate (MTX). Previous studies reported that a co-treatment with MTX and leflunomide can induce additive clinical improvements in RA patients. However, a previous study also demonstrated a reversible elevation of the transaminase levels in up to 63% of patients administered a combination treatment of leflunomide and MTX. This study examined the hepatotoxicity of a combination treatment of MTX and leflunomide. Methods: From March, 2004, to February, 2006, 203 patients who had been treated in 3 rheumatology clinics, Goyang city, South Korea, were reviewed retrospectively. The data showed that 38.92% of patients scored higher than grade 1 hepatotoxicity and 6.90% of patients scored higher than grade 2 according to the NCI/NIH (National Cancer Institute/National Institutes of Health) Common Toxicity Criteria. Results: The median onset time of hepatotoxicity was 5.91 months after treatment. Leflunomide administration was stopped in 39 patients due to several adverse reactions. Among the 39 patients, hepatotoxicity was observed in only 20.51%, suggesting that the hepatotoxicity was not more frequent than expected. Hepatotoxicity did not increase in proportion to the dose of leflunomide and MTX, age, gender, and disease activity. Conclusion: These results indicate that a combined treatment of leflunomide and MTX can be used safely by monitoring the liver enzyme, particularly in the first six months.
Ankylosing spondylitis, Henoch-Schönlein purpura
김현철,전재범,이경아,김담,김희선,김승현 대한류마티스학회 2008 대한류마티스학회지 Vol.15 No.3
Leflunomide is a new disease-modifying drug licensed for treatment of rheumatoid arthritis. Recently, neuropathy has been reported with leflunomide. We report a case of peripheral neuropathy in rheumatoid arthritis treated with leflunomide. Nerve conduction study and electromyogram show sensory-motor polyneuropathy of both upper and lower limbs. Leflunomide medication was discontinued and cholestryamine washout was performed with some improvement in a couple of weeks.
증예(症例) : 류마티스 관절염 환자에서 Leflunomide와 Methotrexate의 병용 투여시 나타난 범혈구 감소증 1예
이일수 ( Il Soo Lee ),성백진 ( Back Jin Seong ),이중철 ( Jung Cheol Lee ),최인기 ( In Key Choi ),강혜미 ( Hye Mi Kang ),민병도 ( Byeng Do Min ),황민호 ( Min Ho Hwang ) 전북대학교 의과학연구소 2006 全北醫大論文集 Vol.30 No.2
DMARDs 단독투여에 반응하지 않는 류마티스 관절염 환자에서 Leflunomide와 MTX의 병용투여를 시도하게 되는 경우에 반드시 정기적인 혈액검사를 하고, 범형구 감소증 발생시 에는 약물 투여를 중단한 후 광범위 항생제, G-CSF를 사용하며, 병용투여 약물과 관련하여 folic acid 의 보충과 약물 배설을 유도하기 위해 charco1과 cholestyramine의 사용을 고려해야 할 것으로 사료된다. The combination therapy of leflunomide and methotrexate(MTX) for whom have inadequate response to long-term therapy of other disease modifying antirheumatic drug is increased recently in rheumatoid arthritis (RA). There are few reports that pancytopenia is more frequently occurred when treated with combination of leflunomide and MTX compared to single therapy. Even if some case be reporedt that the incidence and mortality of pancytopenia is increased after combination therapy, there are not sufficient case report of that. We report a case of pancytopenia due to combination therapy of leflunomide and MTX for 8months, which is improved by using folic acid, cholestyramine and granulocyte colony stimulating factor(G-CSF).
이정화 ( Jung Hwa Lee ),천원석 ( Won Seok Cheon ),서영일 ( Young Il Seo ),엄광석 ( Kwang Seok Eom ),장승훈 ( Seung Hun Jang ),반준우 ( Joon Woo Bahn ),김동규 ( Dong Gyu Kim ),정기석 ( Ki Suck Jung ) 대한결핵 및 호흡기학회 2005 Tuberculosis and Respiratory Diseases Vol.58 No.1
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 dehydr
면역글로불린과 Leflunomide로 치료한 BK 바이러스 신병증
조선영 ( Sun Young Cho ),배정모 ( Jeong Mo Bae ),남우진 ( Woo Jin Nam ),김진건 ( Jin Gun Kim ),김수현 ( Su Hyun Kim ),오동진 ( Dong Jin Oh ),유석희 ( Suk Hee Yu ) 대한내과학회 2011 대한내과학회지 Vol.81 No.4
BK virus nephropathy has emerged as an important cause of renal allograft dysfunction. It affects 1-10% of renal transplant patients and results in significant graft dysfunction in more than 50% of cases. A reduction in the amount of immunosuppressants is not an appropriate treatment option for advanced stage BK nephropathy; therefore, other treatment strategies need to be considered such as cidofovir, leflunomide, and intravenous immunoglobulin (IVIG) in combination with reduced immunosuppression. The use of IVIG may be a valuable treatment option in patients with BK virus nephropathy. We report our experience with IVIG rescue therapy in a patient and the progression of BK nephropathy despite leflunomide therapy. (Korean J Med 2011;81:512-516)