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).

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