Renal Function at Two Years in Liver Transplant Patients Receiving Everolimus: Results of a Randomized, Multicenter Study

In a 24-month prospective, randomized, multicenter, open-label study, de novo liver transplant patients were randomized at 30 days to everolimus (EVR)+Reduced tacrolimus (TAC; n=245), TAC Control (n=243) or TAC Elimination (n=231). Randomization to TAC Elimination was stopped prematurely due to a significantly higher rate of treated biopsy-proven acute rejection (tBPAR). The incidence of the primary efficacy endpoint, composite efficacy failure rate of tBPAR, graft loss or death postrandomization was similar with EVR+Reduced TAC (10.3%) or TAC Control (12.5%) at month 24 (difference -2.2%, 97.5% confidence interval [CI] -8.8%, 4.4%). BPAR was less frequent in the EVR+Reduced TAC group (6.1% vs. 13.3% in TAC Control, p=0.010). Adjusted change in estimated glomerular filtration rate (eGFR) from randomization to month 24 was superior with EVR+Reduced TAC versus TAC Control: difference 6.7mL/min/1.73m2 (97.5% CI 1.9, 11.4mL/min/1.73m2, p=0.002). Among patients who remained on treatment, mean (SD) eGFR at month 24 was 77.6 (26.5)mL/min/1.73m2 in the EVR+Reduced TAC group and 66.1 (19.3)mL/min/1.73m2 in the TAC Control group (p<0.001). Study medication was discontinued due to adverse events in 28.6% of EVR+Reduced TAC and 18.2% of TAC Control patients. Early introduction of everolimus with reduced-exposure tacrolimus at 1 month after liver transplantation provided a significant and clinically relevant benefit for renal function at 2 years posttransplant.