Tacrolimus for the treatment of primary sclerosing cholangitis.
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.


OBJECTIVE
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.
Talwalkar
Jayant A
JA
Division of Gastroenterology & Hepatology, Mayo Clinic College of Medicine, Rochester, MN 55905, USA. talwalkar.jayant@mayo.edu
Gossard
Andrea A
AA
Keach
Jill C
JC
Jorgensen
Roberta A
RA
Petz
Janice L
JL
Lindor
R N Keith D
RN
D000328:Adult; D000368:Aged; D001663:Bilirubin / Q000032:analysis; D015209:Cholangitis, Sclerosing / Q000188:drug therapy*; D004796:Clinical Enzyme Tests; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010352:Patient Dropouts; D010865:Pilot Projects; D016559:Tacrolimus / Q000008:administration & dosage*; D016896:Treatment Outcome
D001663:Bilirubin; D016559:Tacrolimus