Although calcineurin inhibitors are the most commonly used immunosuppressive drugs in liver transplantation, the optimum initial immunosuppression regimen is not known.
In this study, published in the latest issue of the Lancet, the research team compared tacrolimus with microemulsified ciclosporin, in a regimen with standardized concomitant immunosuppressive therapy.
A total of 606 patients, undergoing a first orthotopic liver transplantation, were randomly assigned open-label tacrolimus or microemulsified ciclosporin.
The team regarded the primary outcome as the combined frequency of death, retransplantation, or treatment failure for immunological reasons (whichever occurred first). These data were analyzed by intention to treat.
The research team found 96% of patients received the treatment allocated to them.
The primary outcome was reached in 21% of the patients in the tacrolimus group versus 32% allocated microemulsified ciclosporin (relative risk 0·63).
|Patients reaching primary outcome:|
- tacrolimus = 21%
- ciclosporin = 32%
Death occurred in 17% of patients receiving tacrolimus compared to 24% in those receiving microemulsified ciclosporin. Retransplantations occurred in 4% versus 10%, and treatment failure for immunological reasons in 2% versus 4%.
Furthermore, the relative risk for the composite outcome was in favor of tacrolimus.
The team found the main causes of death in both trial groups to be sepsis and multiple organ failure (10% for both drugs). The main cause of retransplantation was hepatic artery thrombosis (2% versus 6%).
Renal dysfunction and the need for antihypertensive therapy were much the same in both groups.
However, the team discovered tacrolimus to be more diabetogenic.
Dr John O'Grady's team concluded that, "Clinical outcome at 1 year was better with tacrolimus-based immunosuppression than with microemulsified ciclosporin during the first year after liver transplantation".
"Tacrolimus should be the first choice of calcineurin inhibitor for patients receiving their first liver graft".