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
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 | 0.481b |
| eGFR changea, mean±SD | +5.4±13.6 | -0.0±12.8 | 5.4 | 0.003b |
| eGFR LS-meanc [95%CI] | 68.7 [64.5;73.0] | 65.0 [60.6;69.4] | 3.7 [0.2;7.3] | 0.041c |
| On-therapy pop. | n=71 | n=76 | ||
| eGFR mean±SD | 70.3±17.1 | 66.3±15.1 | 4.1 | 0.141b |
| eGFR changea, mean±SD | 8.3±13.1 | -0.9±11.8 | 9.2 | <0.001b |
| eGFR LS-meanc [95%CI] | 71.1 [66.4;75.9] | 63.8 [59.1;68.5] | 7.3 [3.4;11.3] | <0.001c |
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 22, 2024.« Back to 2013 American Transplant Congress