Rapamune怎么样？

To evaluate the safety and efficacy of rapamycin in preventing organ rejection after kidney transplantation, two randomized, double-blind, multicenter controlled trials were conducted. The two trials compared two doses of rapamune oral solution (2 mg and 5 mg once daily) with azathioprine (Trial 1) or placebo (Trial 2) while taking cyclosporine and corticosteroids. Trial 1 was conducted at 38 research sites in the United States, with 719 patients participating. Randomly assigned after transplantation: 284 patients received Rapamune 2 mg/d, 274 patients received Rapamune 5 mg/d, and 161 patients received azathioprine 2-3 mg/kg/d. Trial 2 was conducted at 34 research units in Australia, Canada, Europe and the United States, with 576 patients participating. Before transplantation, 227 patients received Rapamune 2 mg/d, 219 patients received Rapamune 5 mg/d, and 130 patients received placebo. In both trials, antilymphocyte antibody induction therapy was contraindicated. In both trials, the primary efficacy endpoint was the rate of treatment failure within the first 6 months after transplantation. Treatment failure was defined as the first episode of acute rejection (confirmed by biopsy), graft loss, or death.  

In Trial 1, which was expected to be divided by race within the center, treatment failure rates in black patients were similar in the rapamune 2 mg/kg group and the azathioprine group, but lower in the rapamune 5 mg/kg group than in the control group. In Trial 2, which was not expected to be divided by race, treatment failure rates in black patients were similar in the Rapamune and placebo groups. In black patients, the decision to use higher doses of rapamune should be weighed against the dose-dependent adverse effects observed with the 5 mg dose of rapamune. For all subjects in Trials 1 and 2 with serum creatinine measured at 12 months, the mean glomerular filtration rate (GFR) one year after transplantation was calculated using Nankivell's equation. In trials 1 and 2, the mean GFR at 12 months was lower in patients who received cyclosporine and rapamycin (AP) than in patients who received cyclosporine and azathioprine or cyclosporine and placebo. In each treatment arm of Trials 1 and 2, patients who had at least one episode of biopsy-confirmed acute rejection had a lower mean GFR one year after transplantation than those who did not experience rejection. Renal function should be monitored, and appropriate adjustment of immunosuppressive therapy should be considered in patients with rising serum creatinine levels.