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PARIS -- A small biopsy study indicated that treatment with obeticholic acid may be able to stabilize and even reverse primary biliary cholangitis -- apparently confirming biomarker outcomes, researchers suggested here.

Six of 13 patients showed reversal of fibrosis by at least one stage; five patients showed that treatment with obeticholic acid stabilized their condition, and two had progressive disease, reported Christopher Bowlus, MD, of the University of California Davis medical campus in Sacramento.

In reporting the results of the POISE Trial substudy at the International Liver Conference, sponsored by the European Association for the Study of the Liver, Bowlus said, "These results are the first to provide histological evidence that long-term treatment with obeticholic acid may improve disease progression in primary biliary cholangitis."

He and colleagues observed that, in the four patients in the study who had baseline cirrhosis, fibrosis was reversed by at least one stage and three of these patients improved to a stage of fibrosis without cirrhosis.

"What is important here is that the majority of the patients in the study had either improvement in their fibrosis or no worsening after three years of treatment," Bowlus said.

The 13 patients in the study had been included in the parent POISE study; they had volunteered to undergo biopsy so the extent of progression or lack of it could be assessed. "These data are consistent with the previously reported anti-fibrotic effects with obeticholic acid therapy observed in pre-clinical models and in a placebo-controlled study in nonalcoholic steatohepatitis (NASH)," Bowlus said at a press conference.

He noted that primary biliary cholangitis is a chronic liver disease characterized by the inflammation and progressive destruction of bile ductules, cholestatis, eventual cirrhosis and death. "The diagnosis of the disease by using biomarkers makes the need for biopsy to prove the disorder an infrequent occurrence," he said.

Obeticholic acid is a potent, selective farnesoid X receptor agonist developed for the treatment of primary biliary cholangitis, Bowlus explained. The parent POISE trial enrolled 216 patients and showed that daily obeticholic acid achieved greater improvements in alkaline phosphatase and bilirubin, indicators of liver function, after one year of treatment, he said.

To be eligible for the trial substudy, patients were required to have a baseline biopsy within a year from their first entry into the double-blind study. They then had to undergo another biopsy after treatment with obeticholic acid during an open-label extension of the study. There were 27 patients who had a baseline biopsy; 15 patients with paired biopsies and 13 patients for whom clinical data was adequate for analysis, Bowlus reported.

In the biopsy cohort, patients were about 58 years old; 12 of 13 were women; 85% were Caucasian; they had been diagnosed with primary biliary cholangitis for an average of 9.4 years. They were taking obeticholic acid for a mean of 3 years; and the mean time from initial to follow-up biopsy was 3.8 years. Nine patients had advanced fibrosis.

Five serious adverse events occurred in the trial, but that the investigators did not considered them likely related to treatment with obeticholic acid. One of those events was intra-abdominal hemorrhage related to the biopsy procedure, he said.

The effect of obeticholic acid on clinical outcomes in patients with primary biliary cholangitis is under evaluation in the COBALT post-marketing study, he said.

"This is an important observation," said press conference moderator Markus Cornberg, MD, of the Hannover Medical School in Germany. "However, these are small numbers, and there could be sampling bias in the way the study was conducted.

"Nevertheless," he told MedPage Today, "this drug does give us an option for use in patients who do not do well on other medications. We are glad we have an option. But in my view, I don't think this would be used on every patient."

Bowlus told MedPage Today that while the number of patients is small, the outcomes appeared to go in the right direction, "suggesting the finding is real."

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