Premium
High‐dose ursodeoxycholic acid for the treatment of primary sclerosing cholangitis
Author(s) -
Lindor Keith D.,
Kowdley Kris V.,
Luketic Velimir A. C.,
Harrison M. Edwyn,
McCashland Timothy,
Befeler Alex S.,
Harnois Denise,
Jorgensen Roberta,
Petz Jan,
Keach Jill,
Mooney Jody,
Sargeant Carol,
Braaten Julie,
Bernard Tamara,
King Debra,
Miceli Ellen,
Schmoll Jeff,
Hoskin Tanya,
Thapa Prabin,
Enders Felicity
Publication year - 2009
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.23082
Subject(s) - ursodeoxycholic acid , medicine , gastroenterology , placebo , primary sclerosing cholangitis , liver transplantation , clinical endpoint , primary biliary cirrhosis , randomization , hepatology , liver biopsy , transplantation , alkaline phosphatase , randomized controlled trial , biopsy , pathology , disease , biochemistry , chemistry , alternative medicine , enzyme
Previous controlled trials are inconclusive regarding the efficacy of ursodeoxycholic acid (UDCA) for treating primary sclerosing cholangitis (PSC). One hundred fifty adult patients with PSC were enrolled in a long‐term, randomized, double‐blind controlled trial of high‐dose UDCA (28‐30 mg/kg/day) versus placebo. Liver biopsy and cholangiography were performed before randomization and after 5 years. The primary outcome measures were development of cirrhosis, varices, cholangiocarcinoma, liver transplantation, or death. The study was terminated after 6 years due to futility. At enrollment, the UDCA (n = 76) and placebo (n = 74) groups were similar with respect to sex, age, duration of disease, serum aspartate aminotransferase and alkaline phosphatase levels, liver histology, and Mayo risk score. During therapy, aspartate aminotransferase and alkaline phosphatase levels decreased more in the UDCA group than the placebo group ( P < 0.01), but improvements in liver tests were not associated with decreased endpoints. By the end of the study, 30 patients in the UDCA group (39%) versus 19 patients in the placebo group (26%) had reached one of the pre‐established clinical endpoints. After adjustment for baseline stratification characteristics, the risk of a primary endpoint was 2.3 times greater for patients on UDCA than for those on placebo ( P < 0.01) and 2.1 times greater for death, transplantation, or minimal listing criteria ( P = 0.038). Serious adverse events were more common in the UDCA group than the placebo group (63% versus 37% [ P < 0.01]). Conclusion: Long‐term, high‐dose UDCA therapy is associated with improvement in serum liver tests in PSC but does not improve survival and was associated with higher rates of serious adverse events. (H EPATOLOGY 2009.)