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

Thomas Becker, Daniel Foltys, Itxarone Bilbao, Davide D'Amico, Michele Colledan, Angel Bernardos, Susanne Beckebaum, Helena Isoniemi, Jacques Pirenne, J. Járay

Research output: Contribution to journalArticle

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Abstract

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≤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 (≥ 2 fasting plasma glucose values ≥ 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.

Original languageEnglish
Pages (from-to)1689-1694
Number of pages6
JournalTransplantation
Volume86
Issue number12
DOIs
Publication statusPublished - Dec 27 2008

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Mycophenolic Acid
Tacrolimus
Liver Transplantation
Steroids
Leukopenia
daclizumab
Bacterial Infections
Incidence
Graft Survival

Keywords

  • Safety outcomes
  • Steroid-free immunosuppression
  • Tacrolimus monotherapy

ASJC Scopus subject areas

  • Transplantation

Cite this

Patient outcomes in two steroid-free regimens using tacrolimus monotherapy after daclizumab induction and tacrolimus with mycophenolate mofetil in liver transplantation. / Becker, Thomas; Foltys, Daniel; Bilbao, Itxarone; D'Amico, Davide; Colledan, Michele; Bernardos, Angel; Beckebaum, Susanne; Isoniemi, Helena; Pirenne, Jacques; Járay, J.

In: Transplantation, Vol. 86, No. 12, 27.12.2008, p. 1689-1694.

Research output: Contribution to journalArticle

Becker, Thomas ; Foltys, Daniel ; Bilbao, Itxarone ; D'Amico, Davide ; Colledan, Michele ; Bernardos, Angel ; Beckebaum, Susanne ; Isoniemi, Helena ; Pirenne, Jacques ; Járay, J. / Patient outcomes in two steroid-free regimens using tacrolimus monotherapy after daclizumab induction and tacrolimus with mycophenolate mofetil in liver transplantation. In: Transplantation. 2008 ; Vol. 86, No. 12. pp. 1689-1694.
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T1 - Patient outcomes in two steroid-free regimens using tacrolimus monotherapy after daclizumab induction and tacrolimus with mycophenolate mofetil in liver transplantation

AU - Becker, Thomas

AU - Foltys, Daniel

AU - Bilbao, Itxarone

AU - D'Amico, Davide

AU - Colledan, Michele

AU - Bernardos, Angel

AU - Beckebaum, Susanne

AU - Isoniemi, Helena

AU - Pirenne, Jacques

AU - Járay, J.

PY - 2008/12/27

Y1 - 2008/12/27

N2 - 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≤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 (≥ 2 fasting plasma glucose values ≥ 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.

AB - 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≤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 (≥ 2 fasting plasma glucose values ≥ 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.

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KW - Steroid-free immunosuppression

KW - Tacrolimus monotherapy

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