Everolimus with Reduced Calcineurin Inhibitor Exposure in Renal Transplantation

TRANSFORM Investigators

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Abstract

Background Everolimus permits reduced calcineurin inhibitor (CNI) exposure, but the efficacy and safety outcomes of this treatment after kidney transplant require confirmation.

Methods In a multicenter noninferiority trial, we randomized 2037 de novo kidney transplant recipients to receive, in combination with induction therapy and corticosteroids, everolimus with reduced-exposure CNI (everolimus arm) or mycophenolic acid (MPA) with standard-exposure CNI (MPA arm). The primary end point was treated biopsy-proven acute rejection or eGFR <50 ml/min per 1.73 m(2) at post-transplant month 12 using a 10% noninferiority margin.

Results In the intent-to-treat population (everolimus n=1022, MPA n=1015), the primary end point incidence was 48.2% (493) with everolimus and 45.1% (457) with MPA (difference 3.2%; 95% confidence interval, -1.3% to 7.6%). Similar between-treatment differences in incidence were observed in the subgroups of patients who received tacrolimus or cyclosporine. Treated biopsy-proven acute rejection, graft loss, or death at post-transplant month 12 occurred in 14.9% and 12.5% of patients treated with everolimus and MPA, respectively (difference 2.3%; 95% confidence interval, -1.7% to 6.4%). De novo donor-specific antibody incidence at 12 months and antibody-mediated rejection rate did not differ between arms. Cytomegalovirus (3.6% versus 13.3%) and BK virus infections (4.3% versus 8.0%) were less frequent in the everolimus arm than in the MPA arm. Overall, 23.0% and 11.9% of patients treated with everolimus and MPA, respectively, discontinued the study drug because of adverse events.

Conclusions In kidney transplant recipients at mild-to-moderate immunologic risk, everolimus was non-inferior to MPA for a binary composite end point assessing immunosuppressive efficacy and preservation of graft function.

Original languageEnglish
Pages (from-to)1979-1991
Number of pages13
JournalJournal of the American Society of Nephrology
Volume29
Issue number7
DOIs
Publication statusPublished - Jul-2018

Keywords

  • ANTIBODY-MEDIATED REJECTION
  • GLOMERULAR-FILTRATION-RATE
  • KIDNEY-TRANSPLANT
  • ALLOGRAFT DYSFUNCTION
  • MYCOPHENOLIC-ACID
  • RANDOMIZED-TRIAL
  • CANCER INCIDENCE
  • MTOR-INHIBITORS
  • OPEN-LABEL
  • RECIPIENTS

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