Patients with primary biliary cholangitis who received obeticholic acid administered as monotherapy or with ursodiol for 12 months had significant decreases in alkaline phosphatase and total bilirubin levels, according to a study published in the New England Journal of Medicine.
In a double-blind, placebo-controlled trial, Frederick Nevens, MD, PhD, from the Division of Liver and Biliopancreatic Disorders at the University Hospitals KU Leuven in Belgium, and colleagues randomly assigned 217 patients to receive 10 mg of obeticholic acid, 5 mg of obeticholic acid with possible adjustment to 10 mg, or placebo. The patients all previously received ursodiol and had experienced adverse effects or had an inadequate response to the medication.
The researchers defined the primary end point of the study as an alkaline phosphatase level less than 1.67 times the upper limit of the normal range, with a reduction of at least 15% from the start of the study and a total bilirubin level lower than the upper limit of the normal range at 12 months.
The primary end point occurred in 46% of patients who received 5 mg to 10 mg of obeticholic acid, 47% of patients who received 10 mg of obeticholic acid, and 10% of patients in the placebo group.
Patients in the 5-mg group and those in the 10-mg group had significant decreases in alkaline phosphatase levels compared with placebo (least-squares mean, -113 U per liter and -130 U per liter vs -14 U per liter). Patients in the 5-mg and 10-mg groups also had significant decreases in total bilirubin level compared with placebo (-0.02 mg per deciliter and -0.05 mg per deciliter vs 0.12 mg per deciliter).
The researchers also found that changes in noninvasive measures of liver fibrosis did not differ among the treatment groups at 12 months. In addition, pruritus was observed in 56% of patients in the 5-mg group, 68% of patients in the 10-mg group, and 38% of those in the placebo group. Adverse events were observed in 16% of the 5-mg group, 11% of the 10-mg group, and in 4% of the placebo group.
“As in previous studies, treatment with obeticholic acid was associated with a reduction in the HDL cholesterol level,” the study authors wrote. “This finding may result from increased hepatic scavenger receptor B1 expression, which is up-regulated by FXR activation and stimulates hepatic uptake of cholesterol from HDL. Treatment with obeticholic acid was associated with an initial increase in the LDL cholesterol level and persistent decreases in the triglyceride level, which remained stable during the open-label extension. The long-term significance of these findings is unclear.”
- Nevens F, Andreone P, Mazzella G, et al. A placebo-controlled trial of obeticholic acid in primary biliary cholangitis. N Engl J Med. 2016;375(7):631-643. doi:10.1056/nejmoa1509840.