MYCOPHENOLATE MOFETIL IN RENAL-TRANSPLANTATION - RESULTS FROM THE US RANDOMIZED TRIALS

Following promising preclinical and Phase I clinical trials of mycophe nolate mofetil (MMF) in solid organ transplation a series of pivotal r andomized trials were commenced to determine the place of this new imm unosuppressant in clinical kidney transplantation. The trials in the U SA used MMF in combination with prednisone and cyclosporine for reject ion prevention, for the treatment of a first acute rejection, and for the treatment of refractory rejection. Results of the primary end-poin t of the rejection prevention study and from the 12 months follow-up o f the refractory rejection study are now available for analysis. In th e rejection prevention study, which was double-blinded and placebo-con trolled, 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 firs t acute rejection by approximately 50% during the first six months pos t-trans plant. There were also impressive reductions in the use of ste roids and anti-lymphocytic agents. The 2 g daily dose was best tolerat ed and demonstrated a safety profile similar to that of azathioprine. The addition of 3 g MMF daily was effective treatment for refractory a cute rejection and, compared to treatment with intravenous corticoster oids, significantly reduced the subsequent use of anti-lymphocytic age nts. These studies establish MMF as an effective and safe immunosuppre ssant. Its final place in clinical transplantation will be determined by further analysis of these and future studies, and by broadening exp erience with this important addition to the immunosuppressive armament arium.