Everolimus plus reduced-exposure CsA versus mycophenolic acid plus standard-exposure CsA in renal-transplant recipients

Am J Transplant. 2010 Jun;10(6):1401-13. doi: 10.1111/j.1600-6143.2010.03129.x. Epub 2010 Apr 28.

Abstract

Everolimus allows calcineurin-inhibitor reduction without loss of efficacy and may improve renal-transplant outcomes. In a 24-month, open-label study, 833 de novo renal-transplant recipients were randomized to everolimus 1.5 or 3.0 mg/day (target troughs 3-8 and 6-12 ng/mL, respectively) with reduced-exposure CsA, or mycophenolic acid (MPA) 1.44 g/day plus standard-exposure CsA. Patients received basiliximab +/- corticosteroids. The primary endpoint was composite efficacy failure (treated biopsy-proven acute rejection, graft loss, death or loss to follow-up) and the main safety endpoint was renal function (estimated glomerular filtration rate [eGFR], by Modification of Diet in Renal Disease [MDRD]) at Month 12 (last-observation-carried-forward analyses). Month 12 efficacy failure rates were noninferior in the everolimus 1.5 mg (25.3%) and 3.0 mg (21.9%) versus MPA (24.2%) groups. Mean eGFR at Month 12 was noninferior in the everolimus groups versus the MPA group (54.6 and 51.3 vs 52.2 mL/min/1.73 m(2) in the everolimus 1.5 mg, 3.0 mg and MPA groups, respectively; 95% confidence intervals for everolimus 1.5 mg and 3.0 mg vs MPA: -1.7, 6.4 and -5.0, 3.2, respectively). The overall incidence of adverse events was comparable between groups. The use of everolimus with progressive reduction in CsA exposure, up to 60% at 1 year, resulted in similar efficacy and renal function compared with standard-exposure CsA plus MPA.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenal Cortex Hormones
  • Adult
  • Antibodies, Monoclonal
  • Basiliximab
  • Biopsy
  • Enzyme Inhibitors
  • Everolimus
  • Female
  • Humans
  • Immunosuppressive Agents / pharmacology
  • Kidney / drug effects
  • Kidney / pathology
  • Kidney / physiopathology
  • Kidney Function Tests
  • Kidney Transplantation / adverse effects
  • Kidney Transplantation / methods*
  • Male
  • Middle Aged
  • Mycophenolic Acid / administration & dosage*
  • Mycophenolic Acid / therapeutic use
  • Recombinant Fusion Proteins
  • Safety
  • Sirolimus / adverse effects
  • Sirolimus / analogs & derivatives
  • Treatment Outcome

Substances

  • Adrenal Cortex Hormones
  • Antibodies, Monoclonal
  • Enzyme Inhibitors
  • Immunosuppressive Agents
  • Recombinant Fusion Proteins
  • Basiliximab
  • Everolimus
  • Mycophenolic Acid
  • Sirolimus