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Presenter: Anantharaman, Vathsala, Singapore, Singapore
Authors: Vathsala A., Zibari G., Kim Y., Cibrik D., Johnston T., Walker R., Mange K., Panis C., Wang Z., Tedesco-Silva H.
CLINICAL IMMUNOSUPPRESSION - KIDNEY EARLY
A. Vathsala1, G. Zibari2, Y.S. Kim3, D. Cibrik4, T. Johnston5, R. Walker6, K. Mange7, C. Panis7, Z. Wang7, H. Tedesco-silva8
1, Singapore General Hospital, Singapore/SINGAPORE, 2, Willis Knighton - LSU Health Sciences Center, Shreveport/UNITED STATES OF AMERICA, 3, Yonsei University College of Medicine, Seoul/KOREA, 4, University of Michigan, Ann Arbor/MI/UNITED STATES OF AMERICA, 5, University of Kentucky Transplant Center, Lexington/AL/UNITED STATES OF AMERICA, 6, Royal Melbourne Hospital, Melbourne/AUSTRALIA, 7, Novartis Pharmaceuticals Corporation, East Hanover/UNITED STATES OF AMERICA, 8, Hospital do Rim e Hipertensao, Sao Paulo/BRAZIL
Body: Introduction: In renal transplant recipients (RTs), everolimus (EVR) has displayed comparable efficacy to mycophenolic acid (MPA) in the prevention of acute rejection when used with steroids and standard dose cyclosporine (sdCsA). EVR also allows for CsA dose reduction without loss of efficacy when compared with sdCsA regimens. However, the mTOR class has been associated with complications involving wound healing events (WHE) and tissue regeneration in RTs. This study compared effects of 2 dose regimens of EVR with reduced dose CsA (rdCsA) versus a control group receiving MPA with sdCsA on WHE. Methods: A2309 is a 24-month (M), randomized, multi-center, open-label, non-inferiority study comparing 2 regimens of EVR (targeting C0 either at 3–8 ng/mL or 6–12 ng/mL) with rdCsA versus a control group receiving MPA (1.44g/day) with sdCsA. All patients received basiliximab induction and steroids, given according to local practice guidelines. CsA C0 target ranges for the EVR groups were 100–200ng/mL from Day 5, 75–150ng/mL from 2M, 50–100ng/mL from 4M and 25–50ng/mL from 6M. CsA target ranges for the MPA group were 200–300ng/ml from Day 5 and 100–250ng/mL from 2M. Approximately 60% reduction in CsA exposure for both EVR regimens was achieved at 12M versus MPA control group. Primary composite endpoint was non-inferiority of efficacy (Biopsy proven acute rejection (BPAR), graft loss, death, loss to follow-up) between the EVR groups and the MPA control at 12M. Results: Donor and recipient characteristics were comparable between groups. Both the EVR groups were statistically non-inferior to the MPA control group for primary composite efficacy and renal function at 12M. Safety profiles of each regimen were consistent with findings from previous studies. Wound Healing Events as N(%)
EVR 3–8ng/mL | EVR 6–12ng/mL | MPA 1.44g/day | |
N=274 | N=278 | N=273 | |
Total WHEs* | 84(30.6) | 96(34.5) | 67(20.8) |
Vascular lymphocele | 18(6.7) | 31(11.2) | 14(5.1) |
Impaired healing | 5(1.8) | 11(4.0) | 3(1.1) |
Wound dehiscence | 4(1.5) | 9(3.2) | 4(1.5) |
WHE listed as serious AE | 17(6.3) | 22(8.0) | 11(4.2) |
Discontinued due to WHE | 4(1.5) | 7(2.5) | 0(0) |
WHEs needing surgical intervention | 29(10.6) | 35(12.6) | 18(6.6) |
Disclosure: All authors have declared no conflicts of interest.
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