A placebo controlled study of mycophenolate mofetil used in combination with cyclosporine and corticosteroids for the prevention of acute rejection in renal allograft recipients: 1-year results

Purpose: We performed a randomized, double-blind, multicenter, placebo controlled study to compare the efficacy and safety of 2 oral doses of mycophenolate mofetil with placebo for prevention of acute rejection episodes following first or second cadaveric renal allograft transplantation. Materials and Methods: A total of 491 patients were enrolled in the study and randomly allocated to receive placebo (166), 1 gm. mycophenolate mofetil twice daily (165) or 1.5 gm. mycophenolate mofetil twice daily (160). Patients were given concomitant immunosuppression with cyclosporine and corticosteroids. Treatment with mycophenolate mofetil was initiated within 72 hours of transplantation and was continued for at least 1 year. Results: The percentages of patients who experienced biopsy proved rejection or withdrew early from the trial for any reason were significantly reduced with 2 gm. (30.3%) and 3 gm. (38.8%) mycophenolate mofetil compared to placebo (56.0%) (p <0.001). The biopsy proved rejection rates of the placebo, and 2 gm. and 3 gm. mycophenolate mofetil treatment arms were 46.4, 17.6 and 13.8%, respectively. There were fewer patients in the 2 gm. (28.5%) and 3 gm. (24.4%) mycophenolate mofetil groups compared to the placebo (51.8%) group, who received full courses of corticosteroids or antilymphocyte agents for treatment of rejection episodes in the first 6 months after renal transplantation. There was a greater incidence of gastrointestinal adverse events, leukopenia and opportunistic events in the mycophenolate mofetil treatment groups. Conclusions: Mycophenolate mofetil was shown to reduce significantly the number of patients who experienced biopsy proved rejection episodes or treatment failure during the first year after renal transplantation, and was well tolerated.