Effect of induction therapy on outcomes of de novo renal transplant recipients receiving everolimus with reduced-dose calcineurin inhibitor: 24-month results from transform study
Pernin V, Legendre C, Büchler M, Oberbauer R, Vincenti F, Viklicky O, Huynh-Do U, Kim D, Narvekar P, Hernandez-Gutierrez MP, Bernhardt P, Gharbi H, and Kuypers D. Effect of induction therapy on outcomes of de novo renal transplant recipients receiving everolimus with reduced-dose calcineurin inhibitor: 24-month results from transform study. Transplant International 2020; 33:12.
Background: To assess the effect of induction therapy on efficacy and safety outcomes of de novo RTx recipients (RTxR) receiving everolimus with reduced calcineurin inhibitor (EVR+rCNI) vs mycophenolate with standard CNI (MPA + sCNI) in the TRANSFORM (NCT01950819) study.
Methods: In this 24-month (M), phase IV, multicenter, open-label study, adult RTxR stratified by induction type (basiliximab [Bax] or rabbit anti- thymocyte globulin [rATG]) were randomized (RND) to receive EVR + rCNI or MPA + sCNI with steroids. Efficacy assessments were incidence of binary composite of tBPAR or eGFR < 50 mL/min/1.73 m2, incidence of tBPAR, graft loss (GL), or death, and evolution of eGFR up to M24; safety assessments were incidence of adverse events (AE) and infections.
Results: Of 2037 RND patients, 1693 received Bax and 342 received rATG. Consistent with overall data, the EVR + rCNI regimen was noninferior (p < 0.001) to MPA + sCNI for the binary endpoint at M24 for both induction groups. At M24, incidences of tBPAR, GL, and death were comparable between EVR + rCNI and MPA + sCNI arms regardless of induction type. Compared to Bax group, incidence of tBPAR was lower in both arms of rATG group. Mean eGFR was stable from Week 4 to M24 and comparable between arms at M24 for both induction groups. Though the incidence of AE leading to study drug discontinuation was higher in EVR + rCNI arm, the incidence of AE leading to dose adjustment/interruption was higher in MPA + sCNI arm. Incidence of viral infections was lower in EVR + rCNI vs MPA + sCNI arm in both induction groups. Consistent with overall data, incidence of CMV (Bax:8.4% vs 22.6%; rATG:10.1% vs 20.5%) and BKV (Bax:10.1% vs 14.1%; rATG:10.7% vs 20.5%) infections was lower in EVR + rCNI vs MPA + sCNI arm in both induction groups.
Conclusion: Irrespective of the induction type, EVR + rCNI regimen offers comparable efficacy and safety and stable renal function to that of MPA + sCNI regimen up to M24 post-RTx.