Introduction: Long-term steroid administration may predispose liver transplant recipients to infectious and metabolic complications. Maintaining effective immunoprophylaxis while minimizing the negative consequences of steroid therapy could be a key factor in improving clinical outcomes.
Methods: Six hundred two patients were randomized to receive tacrolimus (TAC) immunosuppression with a single-steroid bolus and two doses of daclizumab (DAC) or mycophenolate mofetil (MMF).
Results: The incidence of biopsy-proven acute rejection was 19.7% in the TAC/DAC group and 16.2% in the TAC/MMF group (ns). Three-month patient and graft survival were similar. Steroid use at month-3 was low at 5.5% in the TAC/DAC group and 3.9% in the TAC/MMF group. Significantly higher incidences of causally related adverse events (AEs) and significantly more dose modifications, interruptions, or discontinuations due to an AE were reported with TAC/MMF. Study withdrawal due to leucopenia was significantly higher with TAC/MMF (0.0% vs. 1.7%. P<or=0.05). AEs were generally reported less frequently in the TAC/DAC group. However, specifically headache and supraventricular arrhythmia were significantly higher with TAC/DAC, whereas leucopenia and bacterial infection were significantly higher with TAC/MMF. Laboratory indices of renal function were similar, and increases in serum lipids were negligible in both groups. Incidences of de novo diabetes mellitus (>or=2 fasting plasma glucose values >or=7.0 mmol/L) were low at 9.5% (TAC/DAC) and 11.0% (TAC/MMF).
Conclusion: Both TAC-based regimens allowed optimization of immunoprophylaxis while eliminating some of the negative consequences associated with steroids. Efficacy outcomes were comparable; however, TAC monotherapy after DAC induction was associated with significantly less leucopenia and less bacterial infection than a dual regimen incorporating MMF.