Objectives: This prospective, randomized, multicentre study investigated the efficacy and safety of two tacrolimus-based regimens and their potential to withdraw steroids.
Methods: In total 489 patients were randomised to receive either tacrolimus and MMF (n = 243) or tacrolimus and azathioprine (n = 246) concomitantly with steroids in both treatment groups. The initial oral dose of tacrolimus was 0.2 mg/kg/day, MMF dose was 1 g/day, azathioprine was administered at 1-2 mg/day. Steroids were tapered from 20 mg/day to 5 mg/day. From month 3 onwards, steroids were withdrawn in patients who were free from steroid-resistant rejection and who had serum creatinine concentrations < 160 mumol/L. Study duration was 6 months.
Results: Patient survival at month 6 was 98.3% (Tac/MMF/S) and 98.4% (Tac/Aza/S), graft survival at 6 month was 95.0% (Tac/MMF/S) and 93.5% (Tac/Aza/S). The 6-month incidences of biopsy-proven acute rejection were 18.9% (Tac/MMF/S) compared with 26.8% (Tac/Aza/S), p = 0.038. The 6-month incidences of steroid-resistant acute rejection were 2.1% (Tac/MMF/S) and 4.9% (Tac/Aza/S), p = ns. At the end of month 3, steroid withdrawal was performed in 60.5% (Tac/MMF/S) and 48.8% (Tac/Aza/S) of patients, p < 0.01. During months 4-6, 2.7% of patients in the Tac/MMF group had a biopsy-confirmed acute rejection compared with 0.8% of patients in the Tac/Aza group. In patients who continued to receive steroids, the incidences of biopsy-proven acute rejections during months 4-6 were 3.5% (Tac/MMF/S) and 7.1% (Tac/Aza/S). At study end, the steroid-free patients had an excellent kidney function, the median serum creatinine concentration was 119.5 mumol/L (Tac/MMF) and 115.1 mumol/L (Tac/Aza); the median serum creatinine of the total study group was 130.5 mumol/L (Tac/MMF/S) and 132.8 mumol/L (Tac/Aza/S).
Conclusion: Both tacrolimus regimens are efficacious and safe. The combination of Tacrolimus and MMF achieved a lower rejection rate and permitted a higher proportion of steroid-free patients. The overall incidence of acute rejection was low and kidney function was good.