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 6.7 mL/min/1.73 m2(97.5% CI 1.9, 11.4 mL/min/1.73 m2, p = 0.002). Among patients who remained on treatment, mean (SD) eGFR at month 24 was 77.6 (26.5) mL/min/1.73 m2in the EVR + Reduced TAC group and 66.1 (19.3) mL/min/1.73 m2in 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.

acute graft rejection, adult, anemia, article, ascites, bacterial infection, cardiovascular disease, controlled study, creatinine blood level, cytomegalovirus infection, diabetes mellitus, digestive system ulcer, drug blood level, drug dose reduction, drug exposure, drug safety, drug withdrawal, estimated glomerulus filtration rate, female, glomerulus filtration rate, graft failure, graft recipient, human, hyperlipidemia, incisional hernia, infection rate, interstitial lung disease, kidney failure, kidney function, liver cell carcinoma, liver transplantation, major clinical study, male, multicenter study, mycosis, nephrotic syndrome, neutropenia, open study, peripheral edema, pleura effusion, priority journal, prospective study, proteinuria, randomized controlled trial, stomatitis, thrombocytopenia, thromboembolism, thrombotic thrombocytopenic purpura, treated biopsy proven acute rejection,
American Journal of Transplantation
Erasmus MC: University Medical Center Rotterdam

Saliba, F, de Simone, P, Nevens, F, de Carlis, L, Metselaar, H.J, Beckebaum, S, … Junge, G. (2013). Renal function at two years in liver transplant patients receiving everolimus: Results of a randomized, multicenter study. American Journal of Transplantation, 13(7), 1734–1745. doi:10.1111/ajt.12280