PLACEBO-CONTROLLED STUDY OF MYCOPHENOLATE MOFETIL COMBINED WITH CYCLOSPORINE AND CORTICOSTEROIDS FOR PREVENTION OF ACUTE REJECTION

Preliminary studies suggested that mycophenolate mofetil (MMF), which inhibits proliferation of T and B cells, may reduce the frequency of a cute rejection after renal transplantation. Our randomised, double-bli nd, multicentre, placebo-controlled study compared the efficacy and sa fety of MMF with placebo for prevention of acute rejection episodes af ter first or second cadaveric renal allograft transplantation. 491 pat ients were enrolled; 166 were assigned placebo, 165 MMF 2 g, and 160 M MF 3 g. Patients also received cyclosporin and corticosteroids. Signif icantly fewer (p less than or equal to 0.001) patients had biopsy-prov en rejection or withdrew early from the trial (for any reason) during the first 6 months after transplantation with MMF 2 g (30.3%) or 3 g ( 38.8%) than with placebo (56.0%). The corresponding percentages for bi opsy-proven rejection were 17.0%, 13.8%, and 46.4%. 28.5% of MMF 2 g a nd 24.4% of MMF 3 g patients needed full courses of corticosteroids or antilymphocyte agents for treatment of rejection episodes in the firs t 6 months, compared with 51.8% of placebo recipients. By 6 months, 10 .2%, 6.7%, and 8.8% of the patients in the placebo, MMF 2 g, and MMF 3 g groups, respectively, had died or lost the graft. Overall, the freq uency of adverse events was similar in all treatment groups, although gastrointestinal problems, leucopenia, and opportunistic infections we re more common in the MMF groups and there was a trend for more events in the 3 g than the 2 g group. MMF significantly reduced the rate of biopsy-proven rejection or other treatment failure during the first 6 months after transplantation and was well tolerated, The 3 g dose was somewhat less well tolerated.