Comparison of two steroid‐free regimens ‐ basiliximab/tacrolimus and tacrolimus/mmf ‐ with tacrolimus/mmf/steroid therapy after renal transplantation

AIM: This 3-arm, 6-month, open, prospective study evaluated two steroid-free regimens - basiliximab/tacrolimus (B/Tac) and tacrolimus/MMF (Tac/MMF) - in comparison with triple tacrolimus/MMF/steroid therapy (control). METHODS: Patients were randomized to receive either basiliximab and tacrolimus (B/Tac), tacrolimus and MMF (Tac/MMF); or tacrolimus, MMF, and steroids (control). The initial oral tacrolimus dose was 0.2 mg/kg/day, subsequent doses were adjusted to trough levels of 10-20 ng/mL (days 0-28) and 5-15 ng/mL (days 29-183). The MMF dose was 2 g/day for days 0-14, and 1 g/day thereafter. In the steroid-free arms, 500 mg i.v. prednisolone on day 0, but no maintenance steroids were given. In the control arm, steroids were as follows: 500 mg (day 0), 125 mg (day 1), then tapered from 20 mg/day (days 2-14) to 5 mg/day (>day 43). RESULTS: In total 457 patients were randomized to B/Tac (n=152), Tac/MMF (n=151), and control (n=147), 7 patients were excluded. The study was completed by 82.9% (B/Tac), 94.7% (Tac/MMF), and 91.2% (control) of patients. Patient baseline characteristics were similar in all groups. The incidences of biopsy-proven acute rejection were 26.3% (B/Tac), 30.5% (Tac/MMF), and 8.2% (control), p<0.001(multiple test for comparison with control); B/Tac vs. Tac/MMF, p=ns. The incidences of corticosteroid-resistant acute rejection were 5.3%, 4.0%, and 2.0%, p=ns. Graft survival (94.7%, 96.7%, and 95.9%, p=ns) and patient survival (99.3%, 99.3%, and 100%, p=ns.) were similar in all groups. Median serum creatinine at month 6 was 135.1 µmol/L (B/Tac), 135.0 µmol/L (Tac/MMF) and 122.5 µmol/L (control), median calculated creatinine clearance was 55.4 mL/min, 59.1 mL/min, and 65.3 mL/min, respectively. The overall safety profile was similar in all groups; significant differences were reported for anemia (14.5% vs. 12.6% vs. 24.5%), diarrhea (5.9% vs. 17.9% vs. 12.9%), leukopenia (5.9% vs. 18.5% vs. 7.5%), and tremor (4.6% vs. 7.3% vs. 0.7%), for the B/Tac, Tac/MMF and control groups, respectively. CONCLUSION: Steroid-free immunosuppression using basiliximab induction and tacrolimus monotherapy or tacrolimus and MMF is feasible, however, the incidence of acute rejection was higher in the steroid-free arms compared with a tacrolimus/MMF/steroid combination therapy. The efficacy of B/Tac and Tac/MMF was similar