TY - JOUR
T1 - Tacrolimus for the treatment of primary sclerosing cholangitis
AU - Talwalkar, Jayant A.
AU - Gossard, Andrea A.
AU - Keach, Jill C.
AU - Jorgensen, Roberta A.
AU - Petz, Janice L.
AU - Lindor, R. N.Keith D.
N1 - Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2007/5
Y1 - 2007/5
N2 - Background: Results from a pilot investigation with tacrolimus for primary sclerosing cholangitis (PSC) demonstrated biochemical improvement without excessive drug toxicity. To date, no confirmatory study has been performed. Aims: We sought to determine the safety and efficacy of tacrolimus in PSC. Methods: An open-label, phase II study of tacrolimus 0.05 mg/kg twice daily for 1 year was performed. Target whole-blood concentrations ranged between 3 and 7 ng/ml. Results: A total of 16 patients were enrolled. The median age was 50 years (range, 28-68), with 31% being women. The median serum alkaline phosphatase was 903 U/l, AST 88 U/l, total bilirubin 0.9 mg/dl, and albumin 3.8 g/dl. Based primarily on drug-related adverse events, only eight (50%) patients completed 1 year of therapy. After 1 year of therapy, however, significant improvements in median serum alkaline phosphatase (903 vs. 483, P = 0.0001) and AST levels (88 vs. 78, P = 0.002) were observed in these patients. The median tacrolimus level in patients completing 1 year of therapy was 4.0 ng/ml. Drug-related adverse events, however, were responsible for 31% of participants withdrawing from the study. Conclusions: Despite significant improvements in serum alkaline phosphatase, oral tacrolimus is poorly tolerated in patients with PSC.
AB - Background: Results from a pilot investigation with tacrolimus for primary sclerosing cholangitis (PSC) demonstrated biochemical improvement without excessive drug toxicity. To date, no confirmatory study has been performed. Aims: We sought to determine the safety and efficacy of tacrolimus in PSC. Methods: An open-label, phase II study of tacrolimus 0.05 mg/kg twice daily for 1 year was performed. Target whole-blood concentrations ranged between 3 and 7 ng/ml. Results: A total of 16 patients were enrolled. The median age was 50 years (range, 28-68), with 31% being women. The median serum alkaline phosphatase was 903 U/l, AST 88 U/l, total bilirubin 0.9 mg/dl, and albumin 3.8 g/dl. Based primarily on drug-related adverse events, only eight (50%) patients completed 1 year of therapy. After 1 year of therapy, however, significant improvements in median serum alkaline phosphatase (903 vs. 483, P = 0.0001) and AST levels (88 vs. 78, P = 0.002) were observed in these patients. The median tacrolimus level in patients completing 1 year of therapy was 4.0 ng/ml. Drug-related adverse events, however, were responsible for 31% of participants withdrawing from the study. Conclusions: Despite significant improvements in serum alkaline phosphatase, oral tacrolimus is poorly tolerated in patients with PSC.
KW - Sclerosing cholangitis
KW - Therapy
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U2 - 10.1111/j.1478-3231.2007.01441.x
DO - 10.1111/j.1478-3231.2007.01441.x
M3 - Article
C2 - 17403184
AN - SCOPUS:34047225352
SN - 1478-3223
VL - 27
SP - 451
EP - 453
JO - Liver International
JF - Liver International
IS - 4
ER -