DE NOVO EVEROLIMUS COMBINED WITH REDUCED CYCLOSPORINE EXPOSURE - ANALYSIS OF RENAL FUNCTION AT 12 MONTHS IN RENAL TRANSPLANT RECIPIENTS

USE OF MTOR INHIBITORS AND MPA I

F. Shihab¹, D. Cibrik², Y.S. Kim³, T. Johnston⁴, R. Walker⁵, R. Roland⁶, G. Zibari⁷, K. Mange⁸, C. Panis⁸, Z. Wang⁸, H. Tedesco-silva^9
1, University of Utah Medical Center, Salt Lake City/UT/UNITED STATES OF AMERICA, ², University of Michigan, Ann Arbor/MI/UNITED STATES OF AMERICA, ³, Yonsei University College of Medicine, Seoul/KOREA, ⁴, University of Kentucky Transplant Center, Lexington/AL/UNITED STATES OF AMERICA, ⁵, Royal Melbourne Hospital, Melbourne/AUSTRALIA, ⁶Fn L.pasteura, Robert Roland, Kosice/SLOVAK REPUBLIC, ⁷, Willis Knighton - LSU Health Sciences Center, Shreveport,/UNITED STATES OF AMERICA, ⁸, Novartis Pharmaceuticals Corporation, East Hanover/UNITED STATES OF AMERICA, ⁹, Hospital do Rim e Hipertensao, Sao Paulo/BRAZIL

Body: Introduction: In renal transplant recipients, everolimus (EVR) allows for low exposure of calcineurin inhibitors while maintianing comparable efficacy to standard regimens with mycophenolic acid. Methods: A2309 is a 24-month (M), randomized, multicenter, open-label, non-inferiority study comparing 2 targets for EVR (C0 3–8 ng/mL or C0 6–12 ng/mL) with CsA minimization versus a control group receiving enteric-coated mycophenolate sodium (MPA) 1.44g/day with standard exposure CsA. All patients received basiliximab induction and steroids per center practice. Primary objectives were to determine non-inferiority of the composite efficacy endpoint (biopsy proven acute rejection [BPAR], graft loss, death, loss to follow-up) and of the primary safety endpoint (renal function as estimated using MDRD formula) between the EVR groups and MPA control group at 12M. Results: Donor and recipient characteristics were comparable between the groups. An approximately 60% reduction in CsA exposure for both EVR groups was achieved at 12M versus MPA control group (mean CsA C0: 55, 49 & 137ng/mL for EVR 3–8ng/ml, 6–12ng/ml and MPA groups, respectively). Both EVR groups were statistically non-inferior to the MPA control group for the composite efficacy endpoint and for renal function at 12M. GFR data (in mL/min) for the ITT population.

	EVR 3–8ng/mL N=277	EVR 6–12ng/mL N=279	MPA 1.44g/day N=277
TIME	Mean (SD) Median	Mean (SD) Median	Mean (SD) Median
Baseline	9.3 (7.9) 8.0	9.2 (5.4) 7.9	8.7 (4.5) 7.6
Month 1	59.7 (22.5)* 56.9	54.9 (21.4) 54.6	55.9 (21.4) 52.7
Month 3	57.9 (20.8) 54.7	53.2 (19.7) 51.9	54.5 (20.2) 52.2
Month 6	57.2 (19.9)* 53.6	53.7 (18.6) 52.6	52.1 (18.0) 51.1
Month 9	55.9 (18.3)* 54.8	54.1 (18.8) 53.2	52.5 (17.5) 50.7
Month 12	56.3 (20.1) 55.3	55.0 (19.8) 53.8	54.4 (26.4) 50.8

*p<0.05 for Wilcoxon Rank-Sum EVR 3–8ng/mL vs MPA; p=0.057 for 12M In addition, glomerular filtration rate (GFR) as measured by Cockcroft-Gault formula and by least square means method for repeated measures was better in the EVR groups than in the MPA group at 12 M. The highest proportion of patients who maintained a GFR > 60 mL/min from 1M to 12M was seen in the EVR 3–8ng/ml group. Urinary protein-creatinine ratios were slightly higher in the EVR groups at 12M (314, 543, and 274mg/g for EVR 3–8ng/ml, 6–12ng/ml and MPA groups, respectively) but were clinically insignificant. Conclusion: This study demonstrates that EVR targeted to 3–8ng/ml in combination with reduced CsA exposure allows for benefits in renal function without compromising overall efficacy and safety.

Disclosure: All authors have declared no conflicts of interest.