RANDOMIZED TRIAL COMPARING TACROLIMUS (FK506) AND CYCLOSPORINE IN PREVENTION OF LIVER ALLOGRAFT-REJECTION

Studies in the USA and Japan have shown that tacrolimus (FK506) is a p otent immunosuppressant. To compare the efficacy and safety of tacroli mus-based and conventional cyclosporin-based immunosuppressive regimen s we recruited 545 liver transplant recipients from eight European cen tres into a randomised open trial. Analysis of the data at 12 months p ost-transplant showed that tacrolimus was associated with a significan t reduction in acute, refractory acute, and chronic rejection episodes . The rates were, for acute rejection, tacrolimus 40.5% vs 49.8% cyclo sporin (p=0.040; absolute difference 9.3% [95% Cl 0.9-17.8%]). For ref ractory acute and chronic rejections the comparisons were 0.8% vs 5.3% (p=0.005) and 1.5% vs 5.3% (p=0.032). These results were seen despite significantly lower corticosteroid usage. The incidence of infection was also lower in patients receiving tacrolimus. Patient and graft sur vival 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 metabo lism, 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 con current immunosuppression was administered.