Dose optimization of mycophenolate mofetil when administered with a low dose of tacrolimus in cadaveric renal transplant recipients

Background. Supplementation of immunosuppressive therapy with mycophenolate mofetil (MMF) has been found to reduce the rate of acute rejection in rena l transplantation. We report a dose-finding study for MMF when administered in combination with low-dose tacrolimus and corticosteroid prophylaxis in cadaveric renal transplant recipients. Methods. Two hundred thirty-two patients at 16 centers were enrolled in thi s randomized, parallel-group study. The three treatment groups were tacroli mus and corticosteroids (MMF-0 group, n=82); tacrolimus, corticosteroids, a nd 1 g of MMF daily (MMF-1 g group, n=79); and tacrolimus, corticosteroids, and 2 g of MMF daily (MMF-2 g group, n=71), Study duration was 6 months, a nd patients were followed up for patient and graft survival for 12 months. Results. At 6 months posttransplantation daily doses of 1 g and 2 g of MMF were associated with significantly lower rates of acute rejection compared with tacrolimus alone. The Kaplan-Meier rates were 48.5%, 24.9%, and 22.9%, respectively, for the three treatment groups when acute rejection was dete rmined by clinical criteria (P=0.007). At month 12, patient survival rates were 100%, 97.5%, and 97.2% and graft survival rates were 90.2%, 92.4%, and 93.0% for the MMF-0 group, MMF-1 g group, and the MMF-2 g group, respectiv ely. Gastrointestinal adverse events and leukopenia were higher in the MMF groups, especially in the MMF-2 g group (P<0.05). Conclusions. Low-dose tacrolimus combined with a MMF dose of 1 g daily and corticosteroids provided an optimized efficacy and safety profile. A higher dose of MMF (2 g) was associated with greater toxicity without a significa nt improvement in efficacy.