MYCOPHENOLATE MOFETIL IN RENAL TRANSPLANTATION: 3-YEAR RESULTS FROM THE PLACEBO-CONTROLLED TRIAL1

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Abstract
Background. The European double-blind, placebo-(PLA) controlled study of mycophenolate mofetil (MMF) for prevention of acute renal allograft rejection showed that MMF 2 and 3 g when added to a standard double-drug regimen of cyclosporine and corticosteroids significantly reduced the incidence of acute rejection/treatment failure at 6 months. Our study presents 3-year data for patient and graft survival, and safety in the MMF-treated patients. Methods. The trial included 491 patients who were randomly assigned to receive PLA (n=166), MMF 2 g (n=165), or MMF 3 g (n=160). Patients in the PLA group discontinued taking their PLA medication at 1 year posttransplantation; subsequently, they were followed-up only regarding patient and graft survival and the occurrence of malignancies. Results. The 3-year patient survival was 88.9, 92.7, and 91.8% in the PLA, MMF 2 g, and MMF 3 g groups, respectively. The 3-year graft survival (including death as a cause of graft loss) was 78, 84.8, and 81.2%, respectively. Acute allograft rejection was a principal cause of graft loss in all groups (PLA, 10.8%; MMF 2 g, 4.6%; MMF 3 g, 6.3%). Differences in 3-year graft loss rates (excluding death) and 95% confidence intervals for intent-to-treat comparisons of PLA versus MMF 2 g and 3 g, respectively, were 7.3% (1.1, 14.2) and 3.2% (−3.8, 10.1). This leads to a relative risk of graft loss of 0.55 in the MMF 2 g arm compared with the PLA arm. Acute allograft rejection had a major impact on graft loss at 3 years; 31.5% of patients with biopsy-proven acute rejection within 6 months of transplantation lost their graft by the end of 3 years. In contrast, only 6.6% who had no early acute rejection lost their graft by the end of the 3-year study period. Diarrhea, anemia, and leukopenia were the most common clinically relevant adverse events, occurring predominantly in the MMF 3 g group. Only one patient (MMF 3 g) developed cytomegalovirus tissue-invasive disease after the first year posttransplant. Over the 3-year posttransplant period, 12 patients developed malignancies (5 in the PLA group, 3 in the MMF 2 g group, and 4 in the MMF 3 g group). Conclusions. At 3 years posttransplantation, MMF was associated with 7.6% reduction in the incidence of graft loss (excluding death). These data indicate that MMF treatment not only results in a reduction of the incidence of acute rejections but also leads to reduction of late allograft loss.