Efficacy of Obeticholic Acid in Patients With Primary Biliary Cirrhosis and Inadequate Response to Ursodeoxycholic Acid

作者：Gideon M. Hirschfield, Andrew L. Mason, Velimir A. Luketic, Keith D. Lindor, Stuart C. Gordon, Marlyn J. Mayo, Kris V. Kowdley, Catherine Vincent, Henry C. Bodhenheimer, Albert Parés, Michael Trauner, Hanns–Ulrich Marschall, Luciano Adorini, Cathi Sciacca, T. Beecher-Jones, Erin Castelloe, O. Böhm, Д. А. Шапиро · 发表于：Gastroenterology · 年份：2014 · DOI：10.1053/j.gastro.2014.12.005 · 被引用次数：571 · 研究领域：Liver Diseases and Immunity、Drug Transport and Resistance Mechanisms、Liver Disease Diagnosis and Treatment

BACKGROUND & AIMS: We evaluated the efficacy and safety of obeticholic acid (OCA, α-ethylchenodeoxycholic acid) in a randomized controlled trial of patients with primary biliary cirrhosis who had an inadequate response to ursodeoxycholic acid therapy. METHODS: We performed a double-blind study of 165 patients with primary biliary cirrhosis (95% women) and levels of alkaline phosphatase (ALP) 1.5- to 10-fold the upper limit of normal. Patients were randomly assigned to groups given 10 mg, 25 mg, or 50 mg doses of OCA or placebo, once daily for 3 months. Patients maintained their existing dose of ursodeoxycholic acid throughout the study. The primary outcome was change in level of ALP from baseline (day 0) until the end of the study (day 85 or early termination). We also performed an open-label extension of the trial in which 78 patients were enrolled and 61 completed the first year. RESULTS: OCA was superior to placebo in achieving the primary end point. Subjects given OCA had statistically significant relative reductions in mean ALP from baseline to the end of the study (P < .0001 all OCA groups vs placebo). Levels of ALP decreased 21%-25% on average from baseline in the OCA groups and 3% in the placebo group. Sixty-nine percent (68 of 99) of patients given OCA had at least a 20% reduction in ALP compared with 8% (3 of 37) of patients given placebo (P < .0003). Among secondary end points, levels of γ-glutamyl transpeptidase decreased 48%-63%, on average, among subjects given ...