Improved Renal Function of an Everolimus/Enteric-Coated Mycophenolate Sodium Regimen after Calcineurin Inhibitor Withdrawal in De Novo Renal Transplant Patients: 5 Years Follow-Up of the ZEUS Trial

K. Budde, O. Witzke, C. Sommerer, P. Reinke, U. Eisenberger, E. Paulus, M. Porstner, C. May, W. Arns, F. Lehner

ZEUS Study Group, Germany
Novartis Pharma, Nuremberg, Germany

Meeting: 2013 American Transplant Congress

Abstract number: 18

Aim: To follow-up (FU) on renal function (RF), efficacy and safety after conversion to an Everolimus (EVE)/Enteric-Coated Mycophenolate Sodium (EC-MPS) regimen after cyclosporine A (CsA) withdrawal in de novo kidney allograft recipients at month (Mo)60 after transplantation (Tx).

Methods: In this prospective, open-label, controlled, multi-center study renal Tx patients (pts) were randomized (rdz) at Mo 4.5 post Tx to an immunosuppressive (IS) regimen consisting of either EVE/EC-MPS or CsA/EC-MPS. After completion of core-study (Mo12) pts were included in an observational FU-study.

Results: 300 pts were rdz to either EVE+EC-MPS (n=155) or CsA+EC-MPS (n=145), 221(73.7%) pts completed Mo60 visit. RF expressed as eGFR (Nankivell, ITT) was similar in both groups at baseline (4.5Mo post Tx) with an improvement by +3.7mL/min/1.73m²(95%CI:[+0.2;+7.3];p=0.041) in favor of the EVE regimen at Mo60 compared to +9.8mL/min/1.73m² at Mo12. All pts who remained on the assigned EVE therapy (On-therapy) had a higher improvement of RF +7.3mL/min/1.73m²(95%CI:[+3.4;+11.3]p<0.001). Improved GFR was observed in 69% of pts remaining on EVE therapy vs. only 46% in CsA group (p=0.007).


eGFR Nankivell (ml/min/1.73m²)	EVE	CsA	Difference EVE/CsA	P-value
ITT pop.	n=97	n=97
eGFR mean±SD	68.0±16.8	65.3±15.6	2.7	0.481^b
eGFR change^a, mean±SD	+5.4±13.6	-0.0±12.8	5.4	0.003^b
eGFR LS-mean^c [95%CI]	68.7 [64.5;73.0]	65.0 [60.6;69.4]	3.7 [0.2;7.3]	0.041^c
On-therapy pop.	n=71	n=76
eGFR mean±SD	70.3±17.1	66.3±15.1	4.1	0.141^b
eGFR change^a, mean±SD	8.3±13.1	-0.9±11.8	9.2	<0.001^b
eGFR LS-mean^c [95%CI]	71.1 [66.4;75.9]	63.8 [59.1;68.5]	7.3 [3.4;11.3]	<0.001^c

^aRandomizedTreatmentPeriod ^bWilcoxon Rank-Sum test ^cANCOVA

3 deaths and 3 graft losses were observed in the CsA group vs. 4 deaths and 4 graft losses in the EVE group. Number of pts with infections was 31(20.0%) in EVE vs 21(14.5%) in CsA group, for hospitalisation 35pts (22.6%) in the EVE vs 20pts (13.8%) in CsA group between Mo48 and Mo60. No significant difference in BPAR was reported with 21(13.6%) in the EVE vs. 11(7.5%) in CsA group (p=0.095) from rdz to Mo60.

Conclusions: The conversion to EVE in de novo KTx pts after CNI withdrawal early after Tx reflects a novel therapeutic approach that maintains better RF over a period of 60Mo without compromising efficacy and safety.

Budde, K.: Other, Novartis, Research Funds and/or Honoraria, Roche, Research Funds and/or Honoraria, Pfizer, Research Funds and/or Honoraria, Astellas, Research Funds and/or Honoraria, Bristol-Myers Squibb, Research Funds and/or Honoraria, Hexal, Research Funds and/or Honoraria. Witzke, O.: Other, Novartis, Honoraria, Research Funds, Speaker Fee, Roche, Honoraria, Speaker Fee and Research Grant, Teva, Honoraria and Speaker Fee, Astellas, Honoraria and Speaker Fee. Sommerer, C.: Other, Novartis, Honoraria, Astellas, Honoraria. Eisenberger, U.: Other, Novartis, Speakers Fee. Paulus, E.: Employee, Novartis. Porstner, M.: Employee, Novartis. May, C.: Employee, Novartis. Arns, W.: Other, Novartis, Study Honoraria, Roche, Study Honor

To cite this abstract in AMA style:

Budde K, Witzke O, Sommerer C, Reinke P, Eisenberger U, Paulus E, Porstner M, May C, Arns W, Lehner F. Improved Renal Function of an Everolimus/Enteric-Coated Mycophenolate Sodium Regimen after Calcineurin Inhibitor Withdrawal in De Novo Renal Transplant Patients: 5 Years Follow-Up of the ZEUS Trial [abstract]. Am J Transplant. 2013; 13 (suppl 5). https://atcmeetingabstracts.com/abstract/improved-renal-function-of-an-everolimusenteric-coated-mycophenolate-sodium-regimen-after-calcineurin-inhibitor-withdrawal-in-de-novo-renal-transplant-patients-5-years-follow-up-of-the-zeus-trial/. Accessed November 23, 2024.

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