The efficacy of de novo Everolimus ( Certican ) with reduced-exposure calcineurin inhibitor ( CNI ) was examined in kidney transplant subpopulations from the A2309 study that were identified to be at increased risk for efficacy events.
A2309 was a 24-month, multicenter, open-label trial in which 833 de novo kidney transplant recipients were randomized to Everolimus targeting 3–8 or 6–12 ng/ml with reduced-exposure Cyclosporine, or Mycophenolic acid with standard-exposure Cyclosporine, all with Basiliximab induction.
The composite efficacy endpoint was treated biopsy-proven acute rejection ( BPAR ), graft loss, death, or loss to follow-up.
Cox proportional hazard modeling showed male gender, younger recipient age, black race, delayed graft function, human leukocyte antigen ( HLA ) mismatch greater than or equal to 3 and increasing donor age to be significantly predictive for the composite efficacy endpoint at months 12 or 24 post-transplant.
Cyclosporine exposure was 53–75 % lower, and 46–75 % lower, in patients receiving Everolimus 3–8 ng/ml or receiving Everolimus 6–12 ng/ml, respectively, versus Mycophenolic acid-treated patients.
The incidence of the composite endpoint was similar in all three treatment groups within each subpopulation analyzed. The incidence of treated BPAR was similar with Everolimus 3–8 ng/ml or MPA in all subpopulations, but less frequent with Everolimus 6–12 ng/ml versus Mycophenolic acid in patients with HLA mismatch greater than or equal to 3 ( p = 0.049 ).
This post hoc analysis of a large, randomized trial suggests that a de novo regimen of Everolimus with reduced-exposure Cyclosporine maintains immunosuppressive efficacy even in kidney transplant patients at increased risk for efficacy events despite substantial reductions in Cyclosporine exposure. ( Xagena )
Carmellini M et al, J Nephrol 2015; 28: 633-639