Immunosuppression 2 (Videos Available)

Wednesday July 04, 2018 from 09:45 to 10:45

Room: N-103

517.3 Outcomes on allograft function after 12 months with everolimus plus either tacrolimus or cyclosporine compared to a standard tacrolimus-MPA regimen in de novo renal transplant recipients: The Athena Study

Peter Schenker, Germany

Ruhr-University Bochum

Abstract

Outcomes on Allograft Function after 12 Months with Everolimus Plus either Tacrolimus or Cyclosporine Compared to a Standard Tacrolimus-MPA Regimen in De Novo Renal Transplant Recipients: The Athena Study

Peter Schenker1, Claudia Sommerer1, Barbara Suwelack1, Duska Dragun1, Ingeborg A Hauser1, Oliver Witzke1, Christian Hugo1, Nassim Kamar2, Pierre Merville2, Martina Junge3, Friedrich Thaiss1, Björn Nashan1.

1Athena, Study Group, ., Germany; 2Athena, Study Group, ., France; 3Novartis, Pharma, ., Germany

Athena Study Group.

Background: The ATHENA study was designed to compare efficacy, safety and outcomes on renal function [GFR] of everolimus [EVR] combined with tacrolimus [TAC] or cyclosporine A [CyA] vs. a standard regimen of mycophenolic acid [MPA] +TAC in de novo kidney transplant [KTx] recipients.
Methods: In this prospective, open-label, 12 months [M], randomized study with 15 German and 12 French sites, 612 patients [pts] were randomized 1:1:1 at time of Tx to a regimen of either EVR (C0 target: 3-8ng/ml M1-M12) +TAC (C0 target: 4-8ng/ml M1-M3; 3-5ng/ml M3-M12), or EVR (3-8ng/ml M1-M12) + CyA (C0 target: 75-125ng/ml M1-M3; 50-100ng/ml M3-M12) or control TAC (C0 target: 4-8ng/ml M1-M3; 3-5ng/ml M3-M12) + MPA. Steroids were to be continued in all three treatment groups. Here we report M12 outcomes on allograft function from ITT full analysis set with 208 EVR+TAC vs 199 EVR+CyA vs 205 TAC+MPA pts.
Results: Mean trough levels for EVR were within planned target range throughout the whole study in both EVR groups. Mean CNI trough levels (TAC and CyA) were mostly above intended target range at each visit in all three treatment groups. From randomization to M12 allograft recovery was good in all 3 treatment groups with increase in GFR (Nankivell) as ΔeGFR M1-M12: for EVR+TAC group +6.6ml/min vs EVR+CyA group +9.6ml/min and for TAC+MPA group +7.6 ml/min (not significantly different). Analysis of donor age categories [<35; 35-49; 50-64; >65 years] showed that patients with organs from deceased donors with age >65 years had worst renal allograft outcomes, regardless of treatment (p<0.01 for age). Incidence of graft loss was overall low: 4.8% (10 pts) in EVR+TAC vs 6.5% (13 pts) in EVR+CyA and 2.9% (6 pts) in TAC+MPA group - including 5 primary non-functioning grafts / grafts with cold ischemia lesions in each of the EVR-groups and 1 in TAC+MPA group. There was no difference in urinary protein excretion at M12 between groups. Incidence of pts with proteinuria in nephrotic range [>339mg/mmol] was starting at M1 with 0.5% of TAC+MPA vs 2.4% EVR+TAC vs 3.1% EVR+CyA pts and developed over time to 3.7% of TAC+MPA vs 1.3% of TAC+EVR vs 0.7% of CyA+EVR pts at M12.
Conclusion: ATHENA, the largest European KTx study, showed comparable improvement in renal allograft function between all treatment groups with no difference in measured urinary protein excretion after 12 Mo. Strongest impact on post Tx GFR appears to be determined by donor age, which is shown here for the first time in a large prospective study.



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