Randomised trial comparing tacrolimus (FK506) and cyclosporin in prevention of liver allograft rejection. European FK506 Multicentre Liver Study Group

Lancet. 1994 Aug 13;344(8920):423-8.


Studies in the USA and Japan have shown that tacrolimus (FK506) is a potent immunosuppressant. To compare the efficacy and safety of tacrolimus-based and conventional cyclosporin-based immunosuppressive regimens we recruited 545 liver transplant recipients from eight European centres into a randomised open trial. Analysis of the data at 12 months post-transplant showed that tacrolimus was associated with a significant reduction in acute, refractory acute, and chronic rejection episodes. The rates were, for acute rejection, tacrolimus 40.5% vs 49.8% cyclosporin (p = 0.040; absolute difference 9.3% [95% CI 0.9-17.8%]). For refractory acute and chronic rejections the comparisons were 0.8% vs 5.3% (p = 0.005) and 1.5% vs 5.3% (p = 0.032). There results were seen despite significantly lower corticosteroid usage. The incidence of infection was also lower in patients receiving tacrolimus. Patient and graft survival rates were not significantly different (tacrolimus 82.9% and 77.5%; cyclosporin 77.5% and 72.6%). Safety data were comparable--the most serious events being renal impairment, disturbances of glucose metabolism, and neurological complications--but these events were more common in the tacrolimus group. In this trial tacrolimus had advantages over cyclosporin in respect of lower rejection rates, even though less concurrent immunosuppression was administered.

Publication types

  • Clinical Trial
  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Adolescent
  • Adrenal Cortex Hormones / therapeutic use
  • Adult
  • Aged
  • Chronic Disease
  • Cyclosporine / pharmacology
  • Cyclosporine / therapeutic use*
  • Female
  • Graft Rejection / drug therapy*
  • Graft Rejection / epidemiology
  • Graft Survival / drug effects
  • Humans
  • Immunosuppression / adverse effects
  • Immunosuppression / methods*
  • Incidence
  • Infections / epidemiology
  • Liver Transplantation*
  • Male
  • Middle Aged
  • Survival Rate
  • Tacrolimus / pharmacology
  • Tacrolimus / therapeutic use*


  • Adrenal Cortex Hormones
  • Cyclosporine
  • Tacrolimus