Everolimus versus mycophenolate mofetil in combination with tacrolimus: a propensity score-matched analysis in liver transplantation
Paolo De Simone1, MD PhD, Paola Carrai1, MD, Laura Coletti1, MD PhD, Davide Ghinolfi1, MD PhD,Arianna Precisi2, MD, Daniela Campani3, MD PhD, Piero Marchetti4, MD PhD, and Franco Filipponi1 MD PhD
1. Hepatobiliary surgery and liver transplantation, University of Pisa Medical School Hospital, Via Paradisa 2, I-56124, Pisa, Italy
2. Laboratory, University of Pisa Medical School Hospital, Via Roma 67, I-56126, Pisa, Italy
3. Department of Pathology, University of Pisa Medical School Hospital, Via Paradisa 2, I-56124 Pisa, Italy
4. Department of Clinical and Experimental Medicine, University of Pisa Medical School Hospital, Via Paradisa 2, I–56124, Pisa, Italy
Contact for correspondence:
Paolo De Simone, MD PhD, Hepatobiliary surgery and liver transplantation, University of Pisa Medical School Hospital, Via Paradisa 2, I-56124 Pisa, Italy
Abstract
Background: No trial has investigated the long-term outcome of everolimus (EVR)-incorporating immunosuppression versus tacrolimus (TAC) and mycophenolate mofetil (MMF) after liver transplantation.
Materials and methods: With a propensity score methodology, 178 recipients on TAC+MMF were compared to 178 patients on TAC+EVR.
Results: At a median (interquartile range) follow-up of 45 (46.3) months, the probability of treated biopsy-proven acute rejection, graft loss, and death was 36.6% for MMF and 28.1% for EVR (p=0.0891). Treated biopsy-proven acute rejection was numerically lower for EVR (3.3% versus 7.3%, p=0.09), while adverse events (70.2% versus 58.9%, p=0.02) and drug discontinuations (21.3% versus 11.8%, p=0.01) were significantly higher, in regard to hypercholesterolemia (p=0.001), thrombocytopenia (p=0.0062), and edema (p=0.0107). Patients on MMF showed more hypertension (p=0.0315), tremor (p=0.0006), cytomegalovirus infection (p=0.0165), and malignancies (p=0.0175). EVR was associated with lesser deterioration in mean (SD) renal function at the latest follow-up (-2.2 (1.8) versus -5.1 (3.2) mL/min/1.73m2, t=3.6, p=0.005).
Conclusions: The combination of TAC and EVR provides comparable efficacy versus TAC and MMF. Drug discontinuations and adverse events were higher for patients on EVR, but these latter showed less hypertension, cytomegalovirus infection, and renal dysfunction. The observed reduction in posttransplant malignancies for EVR requires longer follow-up to be confirmed.
