Prednisone withdrawal in kidney transplant recipients on cyclosporine and mycophenolate mofetil - A prospective randomized study

Background. Prospective randomized trials have shown a reduced rate of acut e rejection (AR) in mycophenolate mofetil-treated kidney transplant recipie nts. We hypothesized that this increased protection from AR could allow suc cessful prednisone (P) withdrawal in cyclosporine/mycophenolate mofetil/P-t reated recipients. Methods. A multicenter, prospective, randomized, double-blind trial of P wi thdrawal at 3 months posttransplant was initiated. Entry criteria were: pri mary transplant, adult, no AR by 90 days, mycophenolate mofetil dose greate r than or equal to 2 g/day, cyclosporine dose=5-15 mg/kg/day, P dose=10-15 mg/day, Study participants were randomized to have P tapered over 8 weeks ( beginning at 3 months posttransplant) to 0 vs. 10 mg/day, Prestudy power an alysis determined 500 recipients should be randomized for 80% statistical p ower to test equivalence of the primary endpoint, AR, or treatment failure at 1 year posttransplant, By design, the study was to be stopped if interim data precluded reaching equivalence. An established data safety monitoring board monitored the study. Results, After 266 patients were enrolled, the patient enrollment was stopp ed (after safety monitoring board review) because of excess rejection in th e P withdrawal group, The Kaplan-Meier estimate of the cumulative incidence of rejection or treatment failure within 1 year posttransplant (+/-95% con fidence interval) for the maintenance group was 9.8% (4.4%; treatment failu re, 14.9%); for the withdrawal group, 30.8% (21.0%; 39.3%). Treatment diffe rences in the distribution of time to event were highly significant (P=0.00 07). Of note, risk was higher in blacks (39.6%) versus nonblacks (16.0%) (P <0.001). At 1 year posttransplant, there was no difference between groups i n patient or graft survival, For the patients with functioning grafts at 6 months posttransplant, withdrawal patients had lower cholesterol (P=0.0005) , had higher creatinine (P=0.03), and were less likely to use antihypertens ives (P=0.001). These differences persist to 1 yr posttransplant. Conclusions. We conclude that for recipients on cyclosporine/mycophenolate mofetil/P with no AR at 90 days, the chance of developing subsequent AR is small; if P is tapered and withdrawn, the risk increases (but the majority remain free of acute and chronic rejection). After withdrawal, the risk of AR is different for blacks versus nonblacks, Withdrawal patients had a lowe r cholesterol level and less need for antihypertensives.