Efficacy and Safety of Three Different Treatment Regimens in De Novo Renal Transplant Patients: Follow-Up Results of the HERAKLES Trial at Month 24

M. Zeier, K. Budde, W. Arns, M. Guba, C. Sommerer, H. Neumayer, J. Jacobi, V. Kliem, C. May, D. Baeumer, E. Paulus, O. Witzke, F. Lehner

HERAKLES Study Group, Germany
Novartis Pharma, Nuremberg, Germany

Meeting: 2013 American Transplant Congress

Abstract number: 495

Aim: To compare safety and efficacy of 3 different immunosuppressive (IS) regimens 2years after renal transplantation (Tx).

Methods: 802 patients (pts) were included in this 1year, prospective, open-label, randomized (rdz), controlled, multi-center study. After induction therapy with basiliximab all pts received cyclosporine A (CsA), enteric-coated mycophenolate sodium (EC-MPS) +steroids. 3 months (Mo) post Tx 499pts were rdz 1:1:1 to either a) continue standard (STD) treatment CsA(100-180ng/ml) + EC-MPS(n=166), or convert b) to a calcineurin inhibitor (CNI)-free regimen with everolimus (EVE;5-10ng/ml) + EC-MPS(n=171) or c) to CNI-low regimen with EVE(3-8ng/ml) + reduced CsA(50-75ng/ml) (n=162). All pts continued on steroids. Mo24 follow-up (FU) visit was performed by 131(96%) STD, 132(96%) CNI-free and 125(93%) CNI-low regimen pts of the ongoing FU population (pop).

Results: From rdz to Mo24 BPAR was reported in 17/144(12%) STD, 20/146(14%) CNI-free and in 17/141(12%) CNI-low pts (ITT). 2 deaths (1%) occurred in the CNI-low, none in the other groups. 1(1%) graft loss was observed in the STD and 4(3%) in the CNI-free group. Composite failure (BPAR, death, graft loss, loss to FU) was measured in 19(13%) STD, 22(15%) CNI-free, 20(14%) CNI-low treated pts. Premature discontinuation due to adverse events occurred in 1/147(1%) of STD, 3/148(2%) of CNI-free and 1/141(1%) of CNI-low group pts (safety-pop) from Mo12-24. Renal function expressed as cGFR (Nankivell) was significantly improved by +4.8mL/min/1.73m²(95%CI:[+1.0;+8.6]) in favor of the CNI-free regimen at Mo24(ITT;p=0.014).

Safety Pop. n(%) *	Standard	CNI-free	CNI-low
Infections	32 (21.8)	50 (33.8)	35 (24.8)
Severe infections	6 (4.1)	7 (4.7)	9 (6.4)
Infections with hospitalisation	21 (14.3)	32 (21.6)	28 (19.9)
CMV	4 (2.7)	4 (2.7)	2 (1.4)
BKV	1 (0.7)	2 (1.4)	2 (1.4)
Hospitalisation due to:
Acute rejection	9 (6.1)	10 (6.8)	8 (5.7)
Cardiovascular event	4 (2.7)	2 (1.4)	1 (0.7)
GI event	5 (3.4)	4 (2.7)	3 (2.1)
Malignancy	2 (1.4)	6 (4.1)	1 (0.7)
Metabolic disorder	2 (1.4)	0	0

*during FU (Mo12-24)

Conclusions: The 24Mo results from HERAKLES study showed that the IS regimens using EVE with low-dose or without CNI-exposure reflect an efficacious and safe therapeutic approach offering the opportunity for an individualized IS.

Zeier, M.: Other, Novartis, Speakers Fee, Honoraria, Research Grant, Bristol-Myers Squibb, Speakers Fee, Honoraria, Fresenius Medical Care, Speakers Fee, Honoraria, Abbott, Speakers Fee, Honoraria, Medronic Vascular Inc. Speakers Fee, Honoraria. Budde, K.: Other, Novartis, Research Funds and 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. Arns, W.: Other, Novartis, Study Honoraria, Roche, Study Honoraria, Pfizer, Study Honoraria, Astellas, Study Honoraria. Guba, M.: Other, Novartis, Travel Grant. Sommerer, C.: Other, Novartis, Honoraria, Astellas, Honoraria. Neumayer, H.: Grant/Research Support, Astellas, Roche, Fresenius, Other, Novartis, Research Funds and Honoraria, Bristol-Myers Squibb, Honoraria, Alexion, Honoraria. Jacobi, J.: Grant/Research Support, Novartis. Kliem, V

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