Maintenance Therapy Is Associated With Improved Renal Function

The final results of the Spare the Nephron (STN) study, a multicenter trial investigating a novel kidney-sparing treatment protocol using CellCept (mycophenolate mofetil), showed the CellCept-based regimen in combination with sirolimus (SRL) is associated with improved renal function when compared with the CellCept-based regimen in combination with calcineurin inhibitors (CNI).

Furthermore, the study showed this improvement without increasing the risk of acute rejection, and was tolerated in almost 80 percent of patients. The results were presented today at the American Transplant Congress (ATC) in Toronto.

The STN Trial in kidney transplant recipients examines ways to prevent rejection without damaging kidneys. As transplant patients are living longer, studies suggest that therapies such as CNIs can cause impairment of kidney function, damage to the blood vessels, and filtering capacity of the kidneys. "This study provides strong evidence for the benefits of a CNI-free, CellCept-based regimen," said Thomas Pearson, M.D., lead investigator, Livingston Professor of Surgery, Department of Surgery, Emory University School of Medicine, Atlanta, GA.

The STN trials were conducted at more than 35 transplant centers in the United States and Canada.

"The goal of this study was to optimize the use of immunosuppressants for achieving long-term success," added Dr. Pearson. "The STN Kidney studied the combination of CellCept and SRL with the goal of reducing CNI associated nephrotoxicity therapy to prolong graft and patient survival."

About the Study

This open-label, prospective, multicenter study, randomized 305 patients (maintained on MMF and a CNI) for 30-180 days post-transplant to receive either MMF (1-1.5 g BID) plus SRL (2-10 mg followed by at least 2 mg/day; trough 5-10 ng/mL) and discontinue the CNI (MMF/SRL) or to continue their current regimen (MMF/CNI). Antibody induction and/or corticosteroids were administered according to individual center practices.

Study Results

The 12-month results are from the first 249 patients receiving either the CellCept-based regimen in combination with SRL (n=123) or the CellCept-based regimen in combination with CNI (n=126).

Investigators found acute rejection in 6.5 percent of the patients (8/123) in the CellCept-based regimen in combination with SRL, compared to 7.1 percent of the patients (9/126) in the CellCept-based regimen in combination with CNI.

Mean time from transplant to randomization in both groups was 117 days. Baseline characteristics and measured GFR values were similar in the treatment groups and 98 patients in the CellCept-based regimen in combination with SRL were receiving tacrolimus. Graft loss was experienced in 1.6 percent of patients (2/123) in the CellCept-based regimen in combination with SRL, compared to 2.4 percent of patients (3/126) in the CellCept-based regimen in combination with CNI.

There were no deaths in the CellCept-based regimen in combination with SRL. Three (3/126) patient deaths were remotely related to the CellCept-based regimen in combination with CNI. The number and proportion of patients withdrawn for adverse events at 12 months was 18.7 percent (23/123) in the CellCept-based regimen in combination with SRL, and 7.1 percent (9/126) in the CellCept-based regimen in combination with CNI.

The percent change from baseline in GFR at 12 months was 25.8 percent for patients in the CellCept-based regimen in combination with SRL, compared to 11.3 percent in the CellCept-based regimen in combination with CNI group. Safety outcomes were similar in both groups.

CellCept is indicated for the prophylaxis of organ rejection in patients receiving allogeneic renal, cardiac or hepatic transplants. CellCept should be used concomitantly with cyclosporine and corticosteroids.