Superior Renal Function in an Everolimus-Based Calcineurin Inhibitor Free Regimen Compared to Standard Cyclosporine/Mycophenolate and Low Cyclosporine/Everolimus: Follow-Up of the HERAKLES Study at Month 36.

Field: Medicine (Health Sciences)

Aim: To follow up (FU) on renal function (RF) at month (Mo) 36 after kidney transplantation(Tx) in patients(pts) on immunosuppressive regimen with different calcineurin inhibitor (CNI) exposures. Methods: 802 pts were included in a 1year, prospective, open-label, randomized (RDZ), multi-center study. After induction with basiliximab all pts received cyclosporine A (CsA), enteric-coated mycophenolate sodium (EC-MPS) and steroids. 3Mo post Tx 499 pts were RDZ 1:1:1 to either a) continue standard (STD) CsA(100-180ng/ml) with EC-MPS (n=166), b) convert to a CNI-free regimen with everolimus (EVR;5-10ng/ml) +EC-MPS (n=171) or c) convert to CNI-low regimen CsA(50-75ng/ml) with EVR(3-8ng/ml) (n=162). Mo36 FU visit was performed by 123(89%) STD, 130(95%) CNI-free and 123(94%) CNI-low pts. Results: Median trough levels were: CsA 98ng/ml in STD, 72ng/ml in CNI-low pts and EVR 6.0ng/ml in CNI-free, 5.4ng/ml in CNI-low pts. RF (Nankivell, ITT pop) was similar at RDZ 3Mo post Tx and had significantly improved at Mo12 by +5.6mL/min (95%CI:[+2.9;+8.3];p<0.001) and remained significantly improved by +7.0mL/min in favor of CNI-free regimen at Mo36(p=0.009).Table: No Caption available.58% of CNI-free, 36% of CNI-low and 46% of STD pts had an improvement in RF at Mo36 (p=0.04 CNI-free vs STD). All 3 groups had similar rejection rate since RDZ (13%STD, 15%CNI-free, 14%CNI-low) and overall comparable safety profile. Conclusion: CNI-free as well as reduced CNI in combination with EVR are both efficacious and safe regimen. The CsA trough levels showed that in CNI-low group CNI reduction was not fully met, hence might hampered to translate into better RF compared to STD. However, CNI-free regimen lead to better RF maintained for 3years post Tx. The results of this large trial confirm previous reports of improved RF after CsA withdrawal with EVR in combination with EC-MPS. DISCLOSURE:Budde, K.: Other, BMS, Chiesi, Novartis, Hexal, Pfizer, Veloxis, consultancy agreement, travel support, BMS, Chiesi, Novartis, Hexal, Pfizer, Veloxis, grant/research support, speakers / study honoraria, Effimune, consultancy agreement,, Siemens, AiCuris, Astellas, BmT GmbH, Roche, grant/research/travel support, speakers/study fee. Arns, W.: Other, Novartis, BMS, Roche and Astellas, study honoraria. Sommerer, C.: Grant/Research Support, Novartis, Astellas, Teva. Lehner, F.: Other, Novartis, Astellas, BMS und Roche, research and consultancy fee, speakers fee. Zeier, M.: Grant/Research Support, Novartis, Dietmar Hopp-Stiftung, Other, Novartis, BMS, Fresenius,Medronic Vascular Inc.,, speakers fee / honoraria. Neumayer, H.: Grant/Research Support, Astellas, Novartis, Roche, Fresenius, Other, Alexion Pharma,Bristol Myers Squibb,Novartis,Shire, honoraria. Guba, M.: Grant/Research Support, Novartis, Other, Astellas, travel support. Jacobi, J.: Grant/Research Support, Novartis. Weithofer, P.: Grant/Research Support, Novartis. Baeumer, D.: Employee, Novartis. Sieder, C.: Employee, Novartis. Paulus, E.: Employee, Novartis. Witzke, O.: Other, Amgen, Astellas, Bristol-Myers Squibb, Chiesi, grant/study honoraria,speakers fee,travel expenses, Novartis, Roche, Pfizer and Sanofi, grant/study honoraria,speakers fee,travel expenses.