Mycophenolate mofetil in renal allograft recipients - A pooled efficacy analysis of three randomized, double-blind, clinical studies in prevention of rejection

Background. The search for more effective and less toxic immunosuppressive agents to control transplant rejection has led to the extensive testing of mycophenolate mofetil (MMF) in clinical renal transplantation. Methods. A pooled analysis of three phase III, randomized, double-blind, multicenter clinical trials conducted in the United States, Canada, Europe, and Australia was performed to further characterize the efficacy of MMF in renal allograft recipients. The three studies enrolled a total of 1493 patients. Triple-and quadruple-therapy regimens of cyclosporine, corticosteroids, and standardized MMF dosages with and without antilymphocyte induction were used: MMF in twice-daily doses of 1.0 g or 1.5 g (MMF 2 g or 3 g) was compared with placebo (PLA) or azathioprine (AZA). The primary efficacy endpoint in the individual trials was biopsy-proven rejection or treatment failure at 6 months. This pooled analysis focused on graft loss, patient death, incidence and treatment of rejection episodes, and graft function (serum creatinine) at 1 year. Results. At 1 year, the graft survival rate was 90.4% and 89.2% in the MMF 2 g and 3 g groups, respectively, compared with 87.6% in the PLA/AZA group. This difference was not statistically significant. MMF significantly reduced the incidence of rejection episodes: 40.8% for PLA/AZA patients versus 19.8% and 16.5% for the MMF 2 g and MMF 3 g groups, respectively. Renal function was consistently better for both MMF treatment groups at 3, 6, and 12 months. Conclusions. MMF proved superior to AZA as a post-transplant immunosuppressant in conjunction with cyclosporine and corticosteroids. MMF treated groups showed reduced incidence and severity of rejection episodes, similar graft survival, and better graft function over 12 months.