By Thomas S. May
TORONTO -- June 6, 2008 -- Results of the Spare the Nephron study show that a maintenance regimen based on the combined use of mycophenolate mofetil (MMF) and sirolimus, following calcineurin inhibitor (CNI) withdrawal, is associated with improved renal function in kidney transplant recipients.
The randomised, prospective, multicentre trial evaluated the efficacy and safety of a maintenance immunosuppressive regimen using MMF plus sirolimus compared with MMF and a CNI.
"The goal of this study was to optimise the use of immunosuppressants for achieving long-term success," said lead investigator Thomas Pearson, MD, Emory University School of Medicine, Atlanta, Georgia, in a presentation on June 1 here at the 2008 American Transplant Congress (ATC).
The trial enrolled 305 patients who were maintained on MMF and a CNI for 30 to 180 days after renal transplantation. Subjects were then randomly assigned to either continue their current regimen or to discontinue the CNI and receive MMF at a dose of 1 to 1.5 g BID plus sirolimus 2 to 10 mg followed by at least 2 mg/day (trough 5-10 ng/mL).
Antibody induction and/or corticosteroids were administered according to individual centre practices.
Efficacy endpoints included the proportion of patients with biopsy-proven acute rejection, graft loss, and death at 12 months, and percent change in measured glomerular filtration rate (cold iothalamate) from randomisation.
Acute rejection occurred in 6.5% of patients in the group on MMF/sirolimus compared with 7.1% of patients in the group on MMF/CNI.
Graft loss occurred in 1.6% of patients in the MMF/sirolimus group and in 2.4% of patients in the MMF/CNI group.
There were no deaths in the MMF/sirolimus group. Three patient deaths were remotely related to the MMF/CNI regimen.
The number and proportion of patients withdrawn due to adverse events at 12 months was 18.7% in the MMF/sirolimus arm and 7.1% in the MMF/CNI arm.
The percent change from baseline in glomerular filtration rate at 12 months was 25.8% for patients in the MMF/sirolimus arm and 11.3% in the MMF/CNI arm.
Safety outcomes were similar in both groups.
Based on these results, the investigators concluded that, compared with maintenance therapy using MMF and a CI, maintenance therapy using MMF in combination with sirolimus is associated with improved renal function.
Dr. Pearson noted that the study provides strong evidence for the benefits of a CNI-free, MMF-based regimen.
Funding for this study was provided by Hoffmann-La Roche Inc.
[Presentation title: Efficacy and Safety of Mycophenolate Mofetil (MMF)/Sirolimus (SRL) Maintenance Therapy After Calcineurin Inhibitor (CNI) Withdrawal in Renal Transplant Recipients: Final Results of the Spare-the-Nephron (STN) Trial. Abstract 129]
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