Immunosuppression 1 (Videos Available)

Tuesday July 03, 2018 from 08:30 to 09:30

Room: N-102

401.2 Significant anti-CMV/BKV effect of a modern everolimus-based regimen comparted to standard tacrolimus-MPA regimen in de novo kidney transplant recipients: Athena 12 months data on infections

Duska Dragun, Germany

Full Professor, Managing Director of Department of Nephrology and Critical care medicine
Department of nephrology and critical care medicine
Charité Universitätsmedizin Berlin

Abstract

Significant Anti-CMV/BKV Effect of a Modern Everolimus-Based Regimen Comparted to Standard Tacrolimus-MPA Regimen in de Novo Kidney Transplant Recipients: Athena 12 months Data on Infections

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

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

Athena Study Group.

Background: The ATHENA trial was designed to compare everolimus [EVR] in combination with tacrolimus [TAC] or cyclosporine A [CyA] vs. a standard regimen of mycophenolic acid [MPA] and TAC in de novo kidney transplant [Tx] recipients. Of specific interest was monitoring of infections with main focus on CMV and BKV.
Methods: In this randomized 12 months [M] prospective, open-label study with 15 German and 12 French study sites, in total 612 patients [pts] were randomized 1:1:1 at time of Tx to either EVR (target trough: 3-8ng/ml M1-M12) +TAC (target trough: 4-8ng/ml M1-M3; 3-5ng/ml M3-M12), or EVR (3-8ng/ml M1-M12) + CyA (target trough: 75-125 ng/ml M1-M3; 50-100 ng/ml M3-M12) or to control TAC regimen (target trough: 4-8ng/ml M1-M3; 3-5ng/ml M3-M12) with MPA. All pts received ongoing steroids. Here we present M12 data on infections within ITT population with 208 EVR+TAC pts, 199 EVR+CyA pts and 205 TAC+MPA pts.
Results: From randomization to M12 total incidence of infections was significantly higher in TAC+MPA group with 82% compared to 73% in EVR+TAC and 72% in EVR+CyA treated pts (p<0.05 for both EVR groups). In general, most frequent evet was urinary tract infection with similar incidences across groups: 41% vs 41% vs 40%, respectively. Major differences were seen for viral infections with an incidence of 41% in TAC+MPA vs 26% in EVR+TAC and 12% in EVR+CyA treatment groups (p<0.01). Of specific interest was incidence of BKV and CMV infections: BKV events were reported with 23% in TAC+MPA vs 17% in EVR+TAC vs 9% in EVR+CyA treatment groups (p<0.01) and CMV infections - as well significantly less under EVR treatment - with 21% in TAC+MPA vs 6% in EVR+TAC and 3% in EVR+CyA group (p<0.01). In addition to this more than three-fold difference for CMV infections between TAC+MPA and EVR-treatment, patients with CMV disease and / or recurrent CMV events occurred only in TAC+MPA group, not under EVR-treatment. Matching of CMV-donor / recipient status at baseline was balanced across groups for all risk-constellations and, of note: 3 months CMV-prophylaxis with valganciclovir for D+/R- and D+/R+ pts was requested per protocol.
Conclusion: ATHENA as largest European KTx study confirmed comparable efficacy and safety of all 3 regimens together with beneficial outcomes on viral infections: significantly less viral infections for EVR-based treatment groups compared to TAC+MPA group and a significant, protective effect of EVR-based regimens vs CMV/BKV events was robustly demonstrated.



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