Efficacy and safety of everolimus with reduced tacrolimus in living-donor liver transplant recipients: 12-month results of a randomized multicenter study

In a multicenter, open-label, study, 284 living-donor liver transplant patients were randomized at 305days posttransplant to start everolimus+reduced tacrolimus (EVR+rTAC) or continue standard tacrolimus (TAC Control). EVR+rTAC was non-inferior to TAC Control for the primary efficacy endpoint of treated BPAR, graft loss or death at 12months posttransplant: difference -0.7% (90% CI -5.2%, 3.7%); P<.001 for non-inferiority. Treated BPAR occurred in 2.2% and 3.6% of patients, respectively. The key secondary endpoint, change in estimated glomerular filtration rate (eGFR) from randomization to month 12, achieved non-inferiority (P<.001 for non-inferiority), but not superiority and was similar between groups overall (mean -8.0 vs. -12.1mL/min/1.73m(2), P=.108), and in patients continuing randomized treatment (-8.0 vs. -13.3mL/min/1.73m(2), P=.046). In the EVR+rTAC and TAC control groups, study drug was discontinued in 15.5% and 17.6% of patients, adverse events with suspected relation to study drug occurred in 57.0% and 40.4%, and proteinuria 1g/24h in 9.3% and 0%, respectively. Everolimus did not negatively affect liver regeneration. At 12months, hepatocellular recurrence was only seen in the standard TAC-treated patients (5/62; 8.1%). In conclusion, early introduction of EVR+rTAC was non-inferior to standard tacrolimus in terms of efficacy and renal function at 12months, with hepatocellular carcinoma recurrence only in TAC Control patients. ClinicalTrials.gov Identifier: NCT01888432.