Renal Function at Two Years in Liver Transplant Patients Receiving Everolimus: Results of a Randomized,Multicenter Study |
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| Authors: | F Saliba P De Simone F Nevens L De Carlis H J Metselaar S Beckebaum S Jonas D Sudan L Fischer C Duvoux K D Chavin B Koneru M A Huang W C Chapman D Foltys G Dong P M Lopez J Fung G Junge for the H Study Group |
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| Institution: | 1. Hepatobiliary Center, AP‐HP H?pital Paul Brousse, Université Paris‐Sud, , Villejuif, France;2. General Surgery and Liver Transplantation, Azienda Ospedaliero‐Universitaria Pisana, , Pisa, Italy;3. Department of Hepatology, University Hospital KU Leuven, , Leuven, Belgium;4. Department of General Surgery and Transplantation, Azienda Ospedaliera Niguarda Cà Granda, , Milan, Italy;5. Department of Gastroenterology and Hepatology, Erasmus MC, University Hospital Rotterdam, , Rotterdam, the Netherlands;6. Department of General, Visceral and Transplantation Surgery, University Hospital Essen, , Essen, Germany;7. Department of Transplant Medicine, University Hospital Münster, , Münster, Germany;8. Department of Visceral, Transplantation, Thoracic and Vascular Surgery, University Medical Center Leipzig, , Leipzig, Germany;9. Division of Transplant Surgery, Department of General Surgery, Duke University Medical Center, , Durham, NC;10. Department of Hepatobiliary Surgery and Transplantation, University Medical Center Eppendorf, , Hamburg, Germany;11. Liver Transplant Unit, AP‐HP H?pital Henri Mondor, , Créteil, France;12. Division of Transplant Surgery, Medical University of South Carolina, , Charleston, SC;13. Department of Surgery, University of Medicine and Dentistry—New Jersey Medical School, , Newark, NJ;14. Division of Gastroenterology, Department of Internal Medicine, Henry Ford Hospital, , Detroit, MI;15. Department of Surgery, Washington University School of Medicine, , St Louis, MO;16. Department of Transplant Surgery, University Medical Center, Johannes Gutenberg University, , Mainz, Germany;17. Novartis Pharmaceuticals, , East Hanover, NJ;18. Novartis Pharma AG, , Basel, Switzerland;19. Transplantation Center, Cleveland Clinic, , Cleveland, OH |
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| Abstract: | 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 m2 in the EVR + Reduced TAC group and 66.1 (19.3) mL/min/1.73 m2 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. |
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| Keywords: | Everolimus glomerular filtration rate mTOR inhibitors renal function tacrolimus |
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