BACKGROUND: Primary biliary cholangitis (formerly called primary biliary 
cirrhosis) can progress to cirrhosis and death despite ursodiol therapy. 
Alkaline phosphatase and bilirubin levels correlate with the risk of liver 
transplantation or death. Obeticholic acid, a farnesoid X receptor agonist, has 
shown potential benefit in patients with this disease.
METHODS: In this 12-month, double-blind, placebo-controlled, phase 3 trial, we 
randomly assigned 217 patients who had an inadequate response to ursodiol or who 
found the side effects of ursodiol unacceptable to receive obeticholic acid at a 
dose of 10 mg (the 10-mg group), obeticholic acid at a dose of 5 mg with 
adjustment to 10 mg if applicable (the 5-10-mg group), or placebo. The primary 
end point was an alkaline phosphatase level of less than 1.67 times the upper 
limit of the normal range, with a reduction of at least 15% from baseline, and a 
normal total bilirubin level.
RESULTS: Of 216 patients who underwent randomization and received at least one 
dose of obeticholic acid or placebo, 93% received ursodiol as background 
therapy. The primary end point occurred in more patients in the 5-10-mg group 
(46%) and the 10-mg group (47%) than in the placebo group (10%; P<0.001 for both 
comparisons). Patients in the 5-10-mg group and those in the 10-mg group had 
greater decreases than those in the placebo group in the alkaline phosphatase 
level (least-squares mean, -113 and -130 U per liter, respectively, vs. -14 U 
per liter; P<0.001 for both comparisons) and total bilirubin level (-0.02 and 
-0.05 mg per deciliter [-0.3 and -0.9 μmol per liter], respectively, vs. 0.12 mg 
per deciliter [2.0 μmol per liter]; P<0.001 for both comparisons). Changes in 
noninvasive measures of liver fibrosis did not differ significantly between 
either treatment group and the placebo group at 12 months. Pruritus was more 
common with obeticholic acid than with placebo (56% of patients in the 5-10-mg 
group and 68% of those in the 10-mg group vs. 38% in the placebo group). The 
rate of serious adverse events was 16% in the 5-10-mg group, 11% in the 10-mg 
group, and 4% in the placebo group.
CONCLUSIONS: Obeticholic acid administered with ursodiol or as monotherapy for 
12 months in patients with primary biliary cholangitis resulted in decreases 
from baseline in alkaline phosphatase and total bilirubin levels that differed 
significantly from the changes observed with placebo. There were more serious 
adverse events with obeticholic acid. (Funded by Intercept Pharmaceuticals; 
POISE ClinicalTrials.gov number, NCT01473524; Current Controlled Trials number, 
ISRCTN89514817.).