Combination Improves Renal Graft Function, Study Shows
The study compared a regimen of mycophenolate mofetil (MMF; Cellcept) plus sirolimus and a regimen of MMF plus a CNI (either tacrolimus or cyclosporine) in 298 renal transplant recipients.
“The improvements we saw were significant enough to suggest that we would have fewer graft losses down the road with a Cellcept-based regimen in combination with sirolimus than with a standard CNI-containing regimen,” said lead investigator Shamkant Mulgaonkar, MD, chief of the Renal and Pancreas Transplant Division at St. Barnabas Medical Center in Livingston, N.J.
“However, I don't think this study will change our choice of current immunosuppressant therapy drastically … but it will certainly make most physicians think of sirolimus as one option. This trial provides evidence that a CNI-free regimen can be achieved in selected patients, at least up to one year. Longer-term follow-up is required to firmly established safety and efficacy of this CNI-free regimen.”
The subjects were males and females aged 13-75 years who had received a primary renal allograft from a living or deceased donor in the previous 30-180 days. The investigators excluded subjects who had either a corticosteroid-resistant, biopsy-proven acute rejection or had been treated for acute rejection with antibody therapy in the previous 30 days.
The patients were maintained on MMF + CNI (tacrolimus [TAC] or cyclosporine [CsA]) with or without corticosteroids for 14 days before being randomized to either a continuation of MMF + CNI or to MMF + sirolimus. The medication doses were MMF 1-1.5 mg twice daily, sirolimus 2-10 mg as a loading dose and CNIs or corticosteroids at the individual centers' standards of dosing.
Researchers randomized 148 patients to receive MMF + sirolimus and 150 to the other arm, with 119 receiving MMF/TAC and 31 receiving MMF/CsA. At baseline, the members of the two groups had similar demographic characteristics as well as donor mix, PRA levels, time post-transplant, and fraction receiving induction therapy.
The investigators, who presented study results here at the 2008 American Transplant Congress, observed a significant difference in the mean improvement in measured GFR from baseline to 12 months between the MMF/sirolimus and MMF/TAC groups (27.8% and 6.1%, respectively).
They also observed a significant difference between all three groups' mean change in calculated GFR over one year, with a 7.4% increase for MMF/sirolimus, 1.3% increase for MMF/CNI, and a 0.1% decline for the MMF/TAC subset of CNI patients.
Additionally, the team noted a significant difference favoring sirolimus in the percentage change in calculated creatinine clearance and in the urine-protein-to-creatinine ratio. Seven percent of the patients in the three groups suffered biopsy-proven rejection, whereas similar but smaller percentages experienced graft loss or died. Both study arms had similar adverse events. Proteinuria occurred in 11% and 4% of the MMF/sirolimus and MMF/CNI arms and leucopenia occurred in 22% and 19%, respectively.