Intervention Review

Cyclosporin versus tacrolimus for liver transplanted patients

  1. Elizabeth Haddad2,
  2. Vivian McAlister1,*,
  3. Elizabeth Renouf3,
  4. Richard Malthaner4,
  5. Mette S Kjaer5,
  6. Lise Lotte Gluud6

Editorial Group: Cochrane Hepato-Biliary Group

Published Online: 18 OCT 2006

Assessed as up-to-date: 23 AUG 2006

DOI: 10.1002/14651858.CD005161.pub2


How to Cite

Haddad E, McAlister V, Renouf E, Malthaner R, Kjaer MS, Gluud LL. Cyclosporin versus tacrolimus for liver transplanted patients. Cochrane Database of Systematic Reviews 2006, Issue 4. Art. No.: CD005161. DOI: 10.1002/14651858.CD005161.pub2.

Author Information

  1. 1

    Canadian Forces, 1 Canadian Field Hospital, London, Ontario, Canada

  2. 2

    Surgery, Chatham, Ontario, Canada

  3. 3

    London, Canada

  4. 4

    University of Western Ontario, Division of Thoracic Surgery, London, Ontario, Canada

  5. 5

    Rigshospitalet, Dept. of Hepatology A2121, Copenhagen O, Denmark

  6. 6

    Copenhagen Trial Unit, Centre for Clinical Intervention Research, Department 3344, Rigshospitalet, Copenhagen University Hospital, Cochrane Hepato-Biliary Group, Copenhagen, Denmark

*Vivian McAlister, 1 Canadian Field Hospital, Canadian Forces, C4-212, University Hospital, London, Ontario, N6A 5A5, Canada. vmcalist@uwo.ca.

Publication History

  1. Publication Status: Edited (no change to conclusions)
  2. Published Online: 18 OCT 2006

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Abstract

  1. Top of page
  2. Abstract
  3. Plain language summary
  4. 摘要

Background

Most liver transplant recipients receive either cyclosporin or tacrolimus to prevent rejection. Both drugs inhibit calcineurin phosphatase which is thought to be the mechanism of their anti-rejection effect and principle toxicities. The drugs have different pharmacokinetic profiles and potencies. Several randomised clinical trials have compared cyclosporin and tacrolimus in liver transplant recipients, but it remains unclear which is superior.

Objectives

To evaluate the beneficial and harmful effects of immunosuppression with cyclosporin versus tacrolimus for liver transplanted patients.

Search methods

The Cochrane Hepato-Biliary Group Controlled Trials Register, the Cochrane Central Register of Controlled Trials in The Cochrane Library, MEDLINE, EMBASE, and Science Citation Index Expanded, and conference proceedings were searched (August 2005) to identify relevant randomised clinical trials. Our search included scanning of reference lists in relevant articles and correspondence with investigators and pharmaceutical companies.

Selection criteria

All randomised clinical trials where tacrolimus was compared with cyclosporin for the initial treatment of first-time liver transplant recipients. We included randomised trials irrespective of blinding, language, and publication status.

Data collection and analysis

The primary outcome measure was all-cause mortality. Data were synthesised (fixed-effect model) and results expressed as relative risk (RR), values less than 1.0 favouring tacrolimus, with 95% confidence intervals (CI). Two authors assessed trials for eligibility, quality, and extracted data independently.

Main results

We included 16 randomised trials. The number of deaths was 254 in the tacrolimus group (1899 patients) and 302 in the cyclosporin group (1914 patients). At one year, mortality (RR 0.85, 95% CI 0.73 to 0.99) and graft loss (RR 0.73, 95% CI 0.61 to 0.86) were significantly reduced in tacrolimus-treated recipients. Tacrolimus reduced the number of recipients with acute rejection (RR 0.81, 95% CI 0.75 to 0.88), and steroid-resistant rejection (RR 0.54, 95% CI 0.47 to 0.74) in the first year. Differences were not seen with respect to lymphoproliferative disorder or de-novo dialysis rates, but more de-novo insulin-requiring diabetes mellitus (RR 1.38, 95% CI 1.01 to 1.86) occurred in the tacrolimus group. More patients were withdrawn from cyclosporin therapy than from tacrolimus (RR 0.57, 95% CI 0.49 to 0.66).

Authors' conclusions

Tacrolimus is superior to cyclosporin in improving survival (patient and graft) and preventing acute rejection after liver transplantation, but it increases the risk of post-transplant diabetes. Treating 100 recipients with tacrolimus instead of cyclosporin would avoid acute rejection and steroid-resistant rejection in nine and seven patients, respectively, and graft loss and death in five and two patients, respectively, but four additional patients would develop diabetes after liver transplantation.

 

Plain language summary

  1. Top of page
  2. Abstract
  3. Plain language summary
  4. 摘要

Tacrolimus is superior to cyclosporin in improving patient survival, graft survival, and in preventing acute rejection after liver transplantation, but increases post-transplant diabetes

Almost every liver transplant recipient takes either cyclosporin or tacrolimus to prevent rejection of the graft. This is a review of the clinical trials that compared patients initially prescribed one of the two anti-rejection drugs after liver transplantation. Sixteen trials (3813 participants) were included. The review shows that tacrolimus is marginally better than cyclosporin at preventing patient death and graft loss. Tacrolimus is substantially better than cyclosporin at preventing rejection. No differences were seen between the drugs with respect to adverse events (renal failure, lymphoproliferative disorder) except for diabetes mellitus, which was more common with tacrolimus. After liver transplantation more patients stayed on tacrolimus than on cyclosporin. Tacrolimus is more beneficial than cyclosporine and should be considered the treatment of choice after liver transplantation. This review does not evaluate the benefit or harm of switching from one anti-rejection drug to another.

 

摘要

  1. Top of page
  2. Abstract
  3. Plain language summary
  4. 摘要

背景

比較採用Cyclosporin和tacrolimus治療肝移植病人

多數肝移植受體接受Cyclosporin或者tacrolimus來避免排斥反應。 2種藥物可以抑制鈣調神經磷酸?(calcineurin phosphatase)而產生抗排斥療效和主要毒性。2種藥物具有不同的藥物動力學途徑和效力。一些隨機臨床試驗曾比較肝移植受體使用的Cyclosporin和tacrolimus,但是無法確定哪種藥物較好。

目標

評估Cyclosporin對照tacrolimus對肝移植病人進行免疫抑制的利弊。

搜尋策略

搜尋The Cochrane HepatoBiliary Group Controlled Trials Register, the Cochrane Central Register of Controlled Trials 、Cochrane Library的Cochrane Central Register of Controlled Trials, MEDLINE、EMBASE、 Science Citation Index Expanded以及研討會手冊 (2005年8月) 來找出相關隨機臨床試驗。 我們的搜尋包括掃描相關文章的參考文獻列表,聯繫研究人員和製藥公司。

選擇標準

包括在早期治療中對所有首次肝移植受體使用的tacrolimus對比Cyclosporin的隨機對照試驗。我們收納的隨機試驗不受盲法、語言和發表狀況的限制。

資料收集與分析

初步結果的測量值是全因死亡率。經過合成資料之後(固定效果模型),結果以相對風險度(relative risk ,RR)呈現,及其95%信賴區間(CI)。RR 數值<1.0表示支持tacrolimus。2位作者評估試驗的合格性和品質、獨立摘錄數據。

主要結論

我們收納16個隨機試驗。tacrolimus組的死亡人數是254 (1899 位病人),Cyclosporin組(1914位病人)是302。 一年內,接受tacrolimus的受體明顯降低死亡率 (RR 0.85, 95% CI 0.73 – 0.99)和肝移植損失 (RR 0.73, 95% CI 0.61 – 0.86)。在第一年,tacrolimus降低了急性排斥的受體人數(RR 0.81, 95% CI 0.75 ∼ 0.88)和類固醇治療無效之排斥的受體人數(RR 0.54, 95% CI 0.47 0.74)。 在治療淋巴組織增生疾病或重新透析率(denovo dialysis rates)2方面,2種藥物沒有差異;但是tacrolimus組出現較多的denovo胰島素依賴型糖尿病(RR 1.38, 95% CI 1.01 – 1.86) 。比起tacrolimus (RR 0.57, 95% CI 0.49 0.66), 更多的病人停止使用Cyclosporin治療。

作者結論

tacrolimus在改善存活率(病人和移植物)和避免肝移植後出現急性排斥方面,優於Cyclosporin,但是會增加移植後出現糖尿病的風險。如果100個受體使用tacrolimus(tacrolimus)而不使用Cyclosporin,這將分別使9個和7個病人避免出現急性排斥和類固醇治療無效之排斥,5個和2個病人避免出現肝移植損失和死亡,但是另外有4個病人在肝移植後會患有糖尿病。

翻譯人

此翻譯計畫由臺灣國家衛生研究院(National Health Research Institutes, Taiwan)統籌。

總結

tacrolimus在改善存活率,移植物存活率和避免肝移植後出現急性排斥方面,優於Cyclosporin,但是也提高了移植後出現糖尿病的風險。 幾乎每一個接受Cyclosporin或tacrolimus的肝移植受體都可以避免移植物發生排斥。 本次臨床試驗的文獻回顧比較了在肝移植後,病人首次分別服用2種抗排斥藥物其中之一的效果。 共包括16次試驗 (3813位受試者) 。本次文獻回顧指出,tacrolimus在避免病人死亡和移植物損失方面,明顯優於Cyclosporin。 tacrolimus比Cyclosporin更能有效的避免排斥。除了糖尿病以外,2種藥物在不良事件方面(腎衰竭,淋巴組織增生疾病)沒有差異,糖尿病在tacrolimus中發生的更為普遍。肝移植之後,更多的病人使用tacrolimus而不是Cyclosporin。 tacrolimus比Cyclosporin更有益,應考慮作為肝移植之後的治療選擇。本次文獻回顧沒有評估一種抗排斥藥物轉化為另外一種藥物的利弊。