Mycophenolate mofetil in renal transplantation: results from the U.S. randomized trials

Following promising preclinical and Phase I clinical trials of mycophenolate mofetil (MMF) in solid organ transplantation a series of pivotal randomized trials were commenced to determine the place of this new immunosuppressant in clinical kidney transplantation. The trials in the USA used MMF in combination with prednisone and cyclosporine for rejection prevention, for the treatment of a first acute rejection, and for the treatment of refractory rejection. Results of the primary end-point of the rejection prevention study and from the 12 months follow-up of the refractory rejection study are now available for analysis. In the rejection prevention study, which was double-blinded and placebo-controlled, the addition of either 2 g or 3 g of MMF daily to a standard regimen of cyclosporine and prednisone reduced the incidence of a first acute rejection by approximately 50% during the first six months post-transplant. There were also impressive reductions in the use of steroids and anti-lymphocytic agents. The 2 g daily dose was best tolerated and demonstrated a safety profile similar to that of azathioprine. The addition of 3 g MMF daily was effective treatment for refractory acute rejection and, compared to treatment with intravenous corticosteroids, significantly reduced the subsequent use of anti-lymphocytic agents. These studies establish MMF as an effective and safe immunosuppressant. Its final place in clinical transplantation will be determined by further analysis of these and future studies, and by broadening experience with this important addition to the immunosuppressive armamentarium.