Patient outcomes in two steroid-free regimens using tacrolimus monotherapy after daclizumab induction and tacrolimus with mycophenolate mofetil in liver transplantation.
BACKGROUND
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).


CONCLUSIONS
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.
Becker
Thomas
T
Medizinische Hochschule Hannover, Germany.
Foltys
Daniel
D
Bilbao
Itxarone
I
D'Amico
Davide
D
Colledan
Michele
M
Bernardos
Angel
A
Beckebaum
Susanne
S
Isoniemi
Helena
H
Pirenne
Jacques
J
Jaray
Jenö
J
D000017:ABO Blood-Group System; D000208:Acute Disease; D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D000328:Adult; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000077561:Daclizumab; D004359:Drug Therapy, Combination; D005260:Female; D006084:Graft Rejection / Q000453:epidemiology; D006801:Humans; D007074:Immunoglobulin G / Q000627:therapeutic use*; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D008103:Liver Cirrhosis / Q000601:surgery; D008113:Liver Neoplasms / Q000601:surgery; D016031:Liver Transplantation / Q000276:immunology* / Q000401:mortality / Q000473:pathology; D008297:Male; D009173:Mycophenolic Acid / Q000031:analogs & derivatives* / Q000627:therapeutic use; D018579:Patient Selection; D016019:Survival Analysis; D016559:Tacrolimus / Q000627:therapeutic use*; D016896:Treatment Outcome
D000017:ABO Blood-Group System; D000305:Adrenal Cortex Hormones; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; D000077561:Daclizumab; D009173:Mycophenolic Acid; D016559:Tacrolimus