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 48

K. Budde,¹ C. Sommerer,¹ P. Weithofer,¹ O. Witzke,¹ M. Guba,¹ J. Jacobi,¹ B. Vogt,³ I. Hauser,¹ R. Stahl,¹ P. Reinke,¹ T. Rath,¹ D. Baeumer,² M. Porstner,² M. Zeier,¹ F. Lehner,¹ W. Arns.¹

¹Herakles Study Group, Germany
²Novartis, Pharma, Germany
³Herakles Study Group, Switzerland.

Meeting: 2015 American Transplant Congress

Abstract number: D130

Keywords: Immunosuppression, Kidney transplantation, Multicenter studies, Renal function

Session Information

Session Name: Poster Session D: Kidney Immunosuppression: Drug Minimization

Session Type: Poster Session

Date: Tuesday, May 5, 2015

Session Time: 5:30pm-6:30pm

Presentation Time: 5:30pm-6:30pm

Location: Exhibit Hall E

Aim: To follow up on renal function (GFR) at month (Mo) 48 after kidney transplantation (Tx) in patients (pts) on immunosuppressive regimen with different calcineurin inhibitor (CNI) exposures.

Methods: 802 pts were included in this prospective, open-label, randomized 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 randomized 1:1:1 to either i) continue standard (STD) CsA(100-180ng/ml) with EC-MPS (n=166), ii) convert to a CNI-free regimen with everolimus (EVR;5-10ng/ml) +EC-MPS (n=171) or iii) convert to CNI-low regimen CsA (50-75ng/ml) with EVR(3-8ng/ml) (n=162).

Results: Here data from 48Mo observational follow-up are presented: GFR (Nankivell, ITT) was similar at randomization 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 +6.8mL/min in favor of CNI-free regimen at Mo48(p=0.02). 54% of CNI-free, 36% of CNI-low and 44% of STD pts had an improvement in GFR at Mo48 (p=0.09 CNI-free vs STD). All 3 groups had similar rejection rate since randomization (13%STD, 16%CNI-free, 16%CNI-low) and overall comparable safety profile. Median trough levels at Mo48: CsA 92ng/ml in STD, 80ng/ml in CNI-low pts and EVR 5.1ng/ml in CNI-free, 5.0 ng/ml in CNI-low pts.

Conclusion: CNI-free as well as reduced CNI in combination with EVR are both efficacious and safe regimen. CNI-low group had higher CsA levels than anticipated. The fact that CNI reduction was not fully accomplished might have prevented GFR differences compared to STD. However, CNI-free regimen was associated with better GFR maintained for 4 years post Tx. The results of this large trial confirm previous reports of improved GFR after CsA withdrawal with EVR in combination with EC-MPS.

To cite this abstract in AMA style:

Budde K, Sommerer C, Weithofer P, Witzke O, Guba M, Jacobi J, Vogt B, Hauser I, Stahl R, Reinke P, Rath T, Baeumer D, Porstner M, Zeier M, Lehner F, Arns W. 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 48 [abstract]. Am J Transplant. 2015; 15 (suppl 3). https://atcmeetingabstracts.com/abstract/superior-renal-function-in-an-everolimus-based-calcineurin-inhibitor-free-regimen-compared-to-standard-cyclosporinemycophenolate-and-low-cyclosporineeverolimus-follow-up-of-the-herakles-study-at-mo/. Accessed May 16, 2025.

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