Steroid avoidance with early intensified dosing of enteric-coated mycophenolate sodium: a randomized multicentre trial in kidney transplant recipients

Nephrol Dial Transplant. 2012 Sep;27(9):3651-9. doi: 10.1093/ndt/gfs146. Epub 2012 May 29.

Abstract

Background: Short-term intensified dosing using enteric-coated mycophenolate sodium (EC-MPS) reduces rejection after kidney transplantation without compromising safety and may facilitate steroid avoidance.

Methods: In a 6-month, multicentre open-label trial, 222 de novo kidney transplant recipients at low-immunological risk were randomized to steroid avoidance or maintenance steroids with interleukin (IL)-2 receptor antibody (IL-2RA) induction, EC-MPS (2160 mg/day to Week 6, 1440 mg/day thereafter) and cyclosporine.

Results: The primary end point; treatment failure at Month 6 [biopsy-proven acute rejection (BPAR), graft loss, death or loss to follow-up], occurred in 17.9% (20/112) of steroid-avoidance patients and 14.5% (16/110) of controls (difference 3.4%, 95% confidence interval -6.3 to 13.1, P = 0.47 for superiority testing). BPAR occurred in 11.6 and 7.3% of patients in the steroid-avoidance and control arms, respectively (P = 0.27). Creatinine clearance was similar at Month 6 (steroid-avoidance 56 ± 18 mL/min/1.73 m(2), controls 60 ± 22 mL/min/1.73 m(2), P = 0.34). Cytomegalovirus infection, as reported by investigators, occurred in 12.5% of steroid-avoidance patients and 22.7% of controls (P = 0.045).

Conclusions: A regimen of early intensified EC-MPS dosing with calcineurin inhibitor and IL-2RA induction permits oral steroid avoidance in adult kidney transplant patients at low-immunological risk without compromising efficacy at 6 months' follow-up.

Publication types

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

MeSH terms

  • Adolescent
  • Adrenal Cortex Hormones
  • Adult
  • Aged
  • Cyclosporine / therapeutic use
  • Female
  • Follow-Up Studies
  • Graft Rejection / prevention & control*
  • Humans
  • Immunosuppressive Agents / therapeutic use*
  • Kidney Transplantation*
  • Male
  • Middle Aged
  • Mycophenolic Acid / analogs & derivatives*
  • Mycophenolic Acid / therapeutic use
  • Prognosis
  • Renal Insufficiency, Chronic / therapy*
  • Tablets, Enteric-Coated / therapeutic use*
  • Withholding Treatment*
  • Young Adult

Substances

  • Adrenal Cortex Hormones
  • Immunosuppressive Agents
  • Tablets, Enteric-Coated
  • Cyclosporine
  • Mycophenolic Acid