Obeticholic acid reduced alkaline phosphatase and bilirubin levels in patients with primary biliary cholangitis, according to a phase 3 study published in The New England Journal of Medicine. However, patients taking the drug were more likely to experience pruritis.
“The approval of obeticholic acid for primary biliary cholangitis gives us the first new drug for treating this disease since the approval of ursodeoxycholic acid in 1998,” Keith D. Lindor, MD, FAASLD, executive vice provost and dean at the College of Health Solutions of Arizona State University, told Healio.com/Hepatology. “Obeticholic acid provides an alternative for patients unable to tolerate ursodeoxycholic acid as well as useful adjunct to the approximately one third of treated patients who have inadequate responses to ursodeoxycholic acid.”
Primary biliary cholangitis — previously called primary biliary cirrhosis — can progress to cirrhosis and death despite ursodiol therapy, the researchers wrote. Obeticholic acid — a farnesoid X receptor agonist — has shown benefit in patients with this disease.
Lindor and colleagues performed a 12-month, phase 3 study of 217 patients who had “an inadequate response” to ursodiol. The patients received either placebo, 10 mg of obeticholic acid or 5 mg of obeticholic acid with an adjustment to 10 mg if applicable. The primary endpoint was an alkaline phosphatase level less than 1.67 times the upper limit of the normal range with a reduction of at least 15% from baseline as well as a normal total bilirubin level. The researchers measured alkaline phosphatase and bilirubin levels because they correlate with increased risk for liver transplantation and death.
Of all patients, 93% received ursodiol and background therapy. The primary endpoint was reached in 47% of the 10 mg group, in 46% of the 5 mg to 10 mg group and in 10% of the placebo group (P < .001). The phosphatase level change was –130 U per liter in the 10 mg group, –113 U in the 5 mg to 10 mg group and –14 U in the placebo group (P < .001). The bilirubin level change was –0.02 mg per deciliter in the 10 mg group, –0.05 mg in the 5 mg to 10 mg group and 0.12 mg in the placebo group (P < .001). Pruritus occurred in 68% of the 10 mg group, in 56% of the 5 mg to 10 mg group and in 38% of the placebo group. Further, serious adverse events occurred in 10% of the 10 mg group, in 16% of the 5 mg to 10 mg group and in 4% of the placebo group.
The researchers concluded that obeticholic acid led to a significant decrease in levels of alkaline phosphatase and total bilirubin. However, the treatment led to more serious adverse events, such as pruritis.
“Obeticholic acid dose-dependently increased the incidence of pruritis; [however], the mechanism remains unknown,” Lindor and colleagues wrote. “A multiyear study to assess the effects of obeticholic acid on clinical outcomes in patients with primary biliary cholangitis who have more advanced liver disease is currently enrolling patients.” – by Will Offit
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