[e-med] (2)Monitoring de la ciclosporine et tacrolimus

["dalila abdessemed" <adalila57@hotmail.com>]

Bonsoir

[Review]
Cyclosporin versus tacrolimus for liver transplanted patients

EM Haddad, VC McAlister, E Renouf, R Malthaner, MS Kjaer, LL Gluud

Cochrane Database of Systematic Reviews 2007 Issue 1
Copyright © 2007 The Cochrane Collaboration. Published by John Wiley & Sons, 
Ltd.
DOI: 10.1002/14651858.CD005161.pub2   This version first published online: 
18 October 2006 in Issue 4, 2006
Date of Most Recent Substantive Amendment: 24 August 2006

This record should be cited as: Haddad EM, McAlister VC, 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.

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Abstract

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 strategy
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.

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Plain language summary
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.

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Dalila Abdessemed
adalila57@hotmail.com