Introduction: The ATHENA study [NCT01843348], was conducted to evaluate efficacy and safety of everolimus combined with cyclosporine A [EVR+CyA] or tacrolimus [EVR+TAC] vs. TAC and mycophenolic acid [TAC+MPA] in patients [pts] after de novo kidney transplantation [KTx] ⁽¹⁾.
Materials and Methods: From a total of 15 German [GER] and 12 French [FRA] clinical centers, 612 patients [pts] participated in this 12-months [M] controlled, prospective, open-label, randomized, study. Randomization was done at a 1:1:1 ratio to either [EVR+CyA] (C0: 3-8 ng/mL for M1-12 and C0: 75-125 ng/mL for M1-3; 50-100 ng/mL for M3-12, respectively), [EVR+TAC] (C0: 3-8 ng/mL for M1-12 and C0: 4-8 ng/mL for M1-3; 3-5 ng/mL for M3-12, respectively), or to the control arm [TAC+MPA] (C0: 4-8 ng/mL for M1-3; 3-5 ng/mL for M3-12 and 1440-2000 mg/d M1-12); all with steroids. In this abstract, we present country-based (GER vs. FRA) efficacy and safety data at M12 of N=208, N=199, and N=205 pts treated with EVR+TAC, EVR+CyA, and TAC+MPA, respectively.
Results and Discussion: Interestingly, when comparing the overall intent-to-treat (ITT) findings within the two cohorts GER/FRA, a clear difference was seen. Treated BPAR events (excluding BANFF IA) were recorded at 10.3/6.5%, 16.7/7.3%, and 5.3/13.2% for the EVR+TAC, EVR+CyA, and MPA+TAC groups in the GER/FRA cohorts, respectively. For the key secondary endpoint CMV infections, significantly less occurrences were recorded overall in the EVR-based regimens (in 6.2% of EVR+TAC, 2.5% of EVR+CyA, vs. 20.6% of MPA+TAC treated pts; ITT; p<0.01). Notably, also here we observed a country-dependent difference with overall less CMV infections in the French cohort (8.1/1.6%, 2.8/1.8%, and 22.5/15.1% in the GER/FRA groups for EVR+TAC, EVR+CyA, and MPA+TAC, respectively).
Conclusion: ATHENA, the to date largest randomized and controlled European KTx study, confirmed overall good efficacy and safety across the thee different treatment arms [EVR+TAC, EVR+CyA, and MPA+TAC] . Strikingly, a noteworthy difference regarding treatment attitudes as well as patient and allograft outcomes was observed in pts of the two neighboring European countries Germany and France after de novo KTx. Potential reasons for this observation will be discussed.