Post-transplant immunosuppression with calcineurin inhibitors (CNIs) is associated with impaired renal function. The PROTECT study showed that conversion from CNI to the mTOR-inhibitor everolimus (EVR) at 4 weeks after liver transplantation (LTx) achieves better renal function at 11 months (M) without compromising efficacy. Results of the PROTECT extension period up to 35 M are presented.
In this multicenter, prospective, open label study LTx patients with initial good renal function (calculated GFR ≥50mL/min) 4-8 weeks after liver transplantation (LTx) were randomized to either continued CNI treatment (n=96; standard CNI dose tacrolimus or cyclosporine] ±steroids) or switch to EVR ± steroids (n=98). EVR was adjusted to target trough level of 5-12ng/mL and CNI was withdrawn stepwise until week 16 post randomization. Patients who completed the 11 month core study were followed up to month 35 in the extension phase.
A total of 81 patients (EVR, n=41; CNI, n=40) continued in the follow-up phase. From M12 to M35 further renal function deterioration was observed in the CNI-arm while renal function remained stable in patients receiving EVR. Difference in eGFR between EVR and CNI: Cockcroft-Gault M11: -6.8 mL/min [p=0.240]; M23: -9.8 ml/min [p=0.104]; M35: -10.5 mL/min [p=0.096) and Nankivell formula (M11: -6.6 mL/min [p=0.084]; M23: -8.8 ml/min [p=0.039];M35: -10.5 mL/min [p=0.015]). At M35 there were no significant differences in rates of mortality (EVR: 4.3% vs. CNI: 10.0%, p=0.535), biopsy-proven acute rejection (24.4% vs. 15.8%, p=0.434), and efficacy failure (29.8% vs. 28.2%, p=0.903) were similar. Discontinuation of study treatment due to an AE during the follow-up period was observed in 5 (12.2%) patients on EVR vs. 6 (15.0%) in the CNI group.
Conversion from CNI-based to EVR-based immunosuppression proved to be a safe alternative post-LTx and potentially reduces the risk of end-stage renal disease.
Schlitt, H.: Grant/Research Support, Everolimus. Kaiser, G.: Grant/Research Support, Everolimus. Richter, N.: Grant/Research Support, Everolimus. Heyne, N.: Grant/Research Support, Everolimus. Rauchfuss, F.: Grant/Research Support, Everolimus. Neuhaus, P.: Grant/Research Support, Everolimus. Schemmer, P.: Grant/Research Support, Everolimus. Fischer, L.: Grant/Research Support, Everolimus. Paulus, E.: Employee, Novartis. Mertens, M.: Employee, Novartis. Sterneck, M.: Grant/Research Support, Everolimus.
To cite this abstract in AMA style:Schlitt H, Kaiser G, Richter N, Heyne N, Rauchfuss F, Neuhaus P, Schemmer P, Fischer L, Paulus E, Mertens M, Sterneck M. PROTECT Study: 35 Months of Everolimus Monotherapy vs. Calcineurin Inhibitor-Based Therapy Showed To Be a Safe Alternative with Superior Renal Function in Liver Transplant Recipients, The [abstract]. Am J Transplant. 2013; 13 (suppl 5). https://atcmeetingabstracts.com/abstract/protect-study-35-months-of-everolimus-monotherapy-vs-calcineurin-inhibitor-based-therapy-showed-to-be-a-safe-alternative-with-superior-renal-function-in-liver-transplant-recipients-the/. Accessed October 31, 2020.
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