Five‐year outcomes in liver transplant patients receiving everolimus with or without a calcineurin inhibitor: Results from the CERTITUDE study

Background and Aims To report 5‐year outcomes of the CERTITUDE study. Methods An observational study in patients with liver transplantation (LTx) compared the long‐term impact of immunosuppression (with/without a calcineurin inhibitor) on renal function, cancers, major cardiovascular events (MACEs) and other safety parameters. All patients completing the 6‐month SIMCER study were recruited and analysed according to treatment received at randomization and actual treatment received during the follow‐up. Results Of the 143 enrolled patients, 119 completed the 5‐year follow‐up (everolimus [EVR], n = 55; tacrolimus [TAC], n = 64). The mean absolute change in estimated glomerular filtration rate was not statistically different between both groups (TAC, −15.53 ml/min/1.73 m2 and EVR, –14.56 ml/min/1.73 m2). In the treatment subgroups based on actual treatment received, renal function was preserved better in the EVR subgroup compared with other subgroups (p = .051). Treated biopsy‐proven acute rejection was higher in the EVR group (15.4% vs. 6.4%); however, the majority of events were mild in severity. MACE occurred in 9.2% vs. 14.1% of patients in the EVR and TAC groups respectively (p = .370). De novo cancer was reported in 14 and 5 patients in EVR and TAC groups respectively. Hepatocellular carcinoma (HCC) recurrence was observed in the TAC group alone (n = 4). Adverse events and treatment discontinuation owing to an adverse event were higher in the EVR group. Conclusions The CERTITUDE study demonstrated that EVR‐ and TAC‐based regimens have comparable efficacy, safety and tolerability up to 5 years post‐LTx.