Corticosteroid-free immunosuppression with tacrolimus following induction with daclizumab

A large randomized clinical study

Olivier Boillot, David A. Mayer, Karim Boudjema, Mauro Salizzoni, Bruno Gridelli, Franco Filipponi, Pavel Trunecka, Marek Krawczyk, Pierre Alain Clavien, Christian Ducerf, Carlos Margarit, Raimund Margreiter, José Mir Pallardo, Krister Hoeckerstedt, George Phillipe Pageaux

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Abstract

This open, randomized (1 : 1), multicenter) 3-month study compared a dual tacrolimus plus steroids (Tac / steroids) regimen with a steroid-free immunosuppressive regimen of tacrolimus following daclizumab induction therapy (Tac / Dac) in adult liver transplant recipients. The full analysis set comprised 347 patients in the Tac / steroids group and 351 in the Tac / Dac group. Mean tacrolimus dose during month 3 was 0.11 mg/kg/day in both groups; mean whole-blood trough levels during month 3 were 10.9 ng/mL (Tac / steroids) and 10.6 ng/mL (Tac / Dac). The incidence of biopsy-confirmed acute rejection that required treatment was similar in both groups: 26.5% in the Tac / steroids group and 25.4% in the Tac / Dac group (P = .727). However, the incidence of biopsy-confirmed corticosteroid-resistant acute rejection was higher in the Tac / steroids group than in the Tac / Dac group (6.3 vs. 2.8%; P = .027). Kaplan-Meier estimates of graft survival (92.2 vs. 90.5%) and patient survival (94.5 vs. 93.7%) were similar in both groups. While also the overall adverse event profiles were similar, the incidences of diabetes mellitus (15.3 vs. 5.7%, respectively, P <.001) and cytomegalovirus infection (11.5 vs. 5.1%, respectively; P = .002) were higher in the Tac / steroids group compared with the Tac / Dac group. Mean cholesterol levels increased by 16% in the Tac / steroids group, but were unchanged in the Tac / Dac group during the study. In conclusion, tacrolimus monotherapy following daclizumab induction is an effective and safe regimen, with an advantage over concomitant steroid-maintenance therapy in terms of a lower incidence of diabetes and viral infection, and a lower incidence of steroid-resistant acute rejection.

Original languageEnglish
Pages (from-to)61-67
Number of pages7
JournalLiver Transplantation
Volume11
Issue number1
DOIs
Publication statusPublished - Jan 2005

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Tacrolimus
Immunosuppression
Adrenal Cortex Hormones
Steroids
Incidence
Clinical Studies
daclizumab
Biopsy
Cytomegalovirus Infections
Kaplan-Meier Estimate
Graft Survival
Virus Diseases
Immunosuppressive Agents
Diabetes Mellitus
Therapeutics
Cholesterol
Survival
Liver

ASJC Scopus subject areas

  • Surgery
  • Transplantation

Cite this

Boillot, O., Mayer, D. A., Boudjema, K., Salizzoni, M., Gridelli, B., Filipponi, F., ... Pageaux, G. P. (2005). Corticosteroid-free immunosuppression with tacrolimus following induction with daclizumab: A large randomized clinical study. Liver Transplantation, 11(1), 61-67. https://doi.org/10.1002/lt.20307

Corticosteroid-free immunosuppression with tacrolimus following induction with daclizumab : A large randomized clinical study. / Boillot, Olivier; Mayer, David A.; Boudjema, Karim; Salizzoni, Mauro; Gridelli, Bruno; Filipponi, Franco; Trunecka, Pavel; Krawczyk, Marek; Clavien, Pierre Alain; Ducerf, Christian; Margarit, Carlos; Margreiter, Raimund; Pallardo, José Mir; Hoeckerstedt, Krister; Pageaux, George Phillipe.

In: Liver Transplantation, Vol. 11, No. 1, 01.2005, p. 61-67.

Research output: Contribution to journalArticle

Boillot, O, Mayer, DA, Boudjema, K, Salizzoni, M, Gridelli, B, Filipponi, F, Trunecka, P, Krawczyk, M, Clavien, PA, Ducerf, C, Margarit, C, Margreiter, R, Pallardo, JM, Hoeckerstedt, K & Pageaux, GP 2005, 'Corticosteroid-free immunosuppression with tacrolimus following induction with daclizumab: A large randomized clinical study', Liver Transplantation, vol. 11, no. 1, pp. 61-67. https://doi.org/10.1002/lt.20307
Boillot, Olivier ; Mayer, David A. ; Boudjema, Karim ; Salizzoni, Mauro ; Gridelli, Bruno ; Filipponi, Franco ; Trunecka, Pavel ; Krawczyk, Marek ; Clavien, Pierre Alain ; Ducerf, Christian ; Margarit, Carlos ; Margreiter, Raimund ; Pallardo, José Mir ; Hoeckerstedt, Krister ; Pageaux, George Phillipe. / Corticosteroid-free immunosuppression with tacrolimus following induction with daclizumab : A large randomized clinical study. In: Liver Transplantation. 2005 ; Vol. 11, No. 1. pp. 61-67.
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abstract = "This open, randomized (1 : 1), multicenter) 3-month study compared a dual tacrolimus plus steroids (Tac / steroids) regimen with a steroid-free immunosuppressive regimen of tacrolimus following daclizumab induction therapy (Tac / Dac) in adult liver transplant recipients. The full analysis set comprised 347 patients in the Tac / steroids group and 351 in the Tac / Dac group. Mean tacrolimus dose during month 3 was 0.11 mg/kg/day in both groups; mean whole-blood trough levels during month 3 were 10.9 ng/mL (Tac / steroids) and 10.6 ng/mL (Tac / Dac). The incidence of biopsy-confirmed acute rejection that required treatment was similar in both groups: 26.5{\%} in the Tac / steroids group and 25.4{\%} in the Tac / Dac group (P = .727). However, the incidence of biopsy-confirmed corticosteroid-resistant acute rejection was higher in the Tac / steroids group than in the Tac / Dac group (6.3 vs. 2.8{\%}; P = .027). Kaplan-Meier estimates of graft survival (92.2 vs. 90.5{\%}) and patient survival (94.5 vs. 93.7{\%}) were similar in both groups. While also the overall adverse event profiles were similar, the incidences of diabetes mellitus (15.3 vs. 5.7{\%}, respectively, P <.001) and cytomegalovirus infection (11.5 vs. 5.1{\%}, respectively; P = .002) were higher in the Tac / steroids group compared with the Tac / Dac group. Mean cholesterol levels increased by 16{\%} in the Tac / steroids group, but were unchanged in the Tac / Dac group during the study. In conclusion, tacrolimus monotherapy following daclizumab induction is an effective and safe regimen, with an advantage over concomitant steroid-maintenance therapy in terms of a lower incidence of diabetes and viral infection, and a lower incidence of steroid-resistant acute rejection.",
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