No abstract

Two prospective, randomized studies evaluated everolimus 1.5 vs. 3 mg/day with steroids and lowexposure cyclosporine (CsA) (C 2 monitoring) in de novo renal transplant patients. Everolimus dosing was adjusted to maintain a minimum trough level of 3 ng/mL. Study 1 (A2306; n = = 237) had no induction therapy; in Study 2 (A2307; n = = 256) basiliximab was administered (Days 0 and 4). The primary endpoint was renal function at 6 months. CsA C 2 target levels, initially 1200 ng/mL in Study 1 and 600 ng/mL in Study 2, were tapered over time post-transplant. Median creatinine levels in Study 1 were 133 and 132 lmol/L at 6 months in the 1.5 and 3 mg/day groups, respectively, and 130 lmol/L in both groups in Study 2. Biopsyproven acute rejection (BPAR) occurred in 25.0% and 15.2% of patients in the 1.5 and 3 mg/day groups in Study 1, and 13.7% and 15.1% in Study 2. Incidence of BPAR was significantly higher in patients with an everolimus trough < < 3 ng/mL. There were no significant between-group differences in the composite endpoint of BPAR, graft loss or death, nor any significant between-group differences in adverse events in either study. Concentration-controlled everolimus with lowexposure CsA provided effective protection against rejection with good renal function.

Acute rejection was significantly lower in the ATG-Tac group compared with the ATG-CsA and Tac triple groups. Significantly more hematologic and infectious adverse events were observed in both ATG induction groups.

Basiliximab immunoprophylaxis is safe, well tolerated, and shows a trend toward reduction in number of acute rejection episodes in renal transplant patients receiving cyclosporine, mycophenolate mofetil, and steroids.

Total basiliximab doses of 40-60 mg were well tolerated, nonimmunogenic, and estimated to provide immunoprophylaxis to cover the first posttransplant month.