title: Mycophenolate mofetil in renal allograft recipients: a pooled efficacy analysis of three randomized, double-blind, clinical studies in prevention of rejection. The International Mycophenolate Mofetil Renal Transplant Study Groups.
abstract: 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.
authors.affiliation: University of Alberta Hospitals, Edmonton, Canada.
authors.forename: P
authors.initials: P
authors.lastname: Halloran
authors.forename: T
authors.initials: T
authors.lastname: Mathew
authors.forename: S
authors.initials: S
authors.lastname: Tomlanovich
authors.forename: C
authors.initials: C
authors.lastname: Groth
authors.forename: L
authors.initials: L
authors.lastname: Hooftman
authors.forename: C
authors.initials: C
authors.lastname: Barker
mesh_terms: D000328:Adult; D016572:Cyclosporine / Q000627:therapeutic use; D004311:Double-Blind Method; D005260:Female; D006084:Graft Rejection; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007668:Kidney / Q000503:physiopathology; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000031:analogs & derivatives* / Q000627:therapeutic use; D014184:Transplantation, Homologous
chemical_list: D007166:Immunosuppressive Agents; D016572:Cyclosporine; D009173:Mycophenolic Acid