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 posttransplant 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.
RCT Entities:
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, patientdeath, 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/AZApatients 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 posttransplant 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.
Authors: R Shapiro; M L Jordan; V P Scantlebury; C Vivas; J W Marsh; J McCauley; J Johnston; P Randhawa; W Irish; H A Gritsch; R Naraghi; T R Hakala; J J Fung; T E Starzl Journal: Transplantation Date: 1999-02-15 Impact factor: 4.939
Authors: Bronwyn A Atcheson; Paul J Taylor; David W Mudge; David W Johnson; Carmel M Hawley; Scott B Campbell; Nicole M Isbel; Peter I Pillans; Susan E Tett Journal: Br J Clin Pharmacol Date: 2005-03 Impact factor: 4.335