BOSTON – Patients with primary biliary cholangitis (PBC) who have compensated cirrhosis fared just as well on obeticholic acid (OCA) as did PBC patients without cirrhosis, according to an analysis of data from POISE, the pivotal clinical trial for approval of OCA for PBC.
The POISE trial included 36 individuals with PBC and compensated cirrhosis, since cirrhosis “is an endpoint for virtually all liver diseases,” John Vierling, MD, said in a
To see how this group fared, Dr. Vierling and his coinvestigators performed a post hoc analysis of the POISE data to examine OCA’s safety and efficacy for patients with compensated cirrhosis. Patients with decompensated cirrhosis were not included in the trial.
, chief of hepatology at Baylor College of Medicine, Houston, noted that investigators worked hard to set the bar high for inclusion in the group with cirrhosis, to achieve very high specificity. “We did this by using very stringent criteria of liver biopsy, or transient elastography adjusted for a very high range of kilopascals required to diagnose cirrhosis in cholestatic patients,” he said. To be included, patients also had to have elevated total bilirubin levels and a baseline alkaline phosphatase level greater than five times the upper limit of normal.
Statistically, the patients were evenly distributed across the placebo arm and the two treatment arms, one of which dosed OCA at 10 mg/day; the other treatment arm had flexible dosing at 5-10 mg/day.
The POISE trial used a composite primary efficacy endpoint of achieving an alkaline phosphatase (ALP) less than 1.67 times the upper limit of normal, with total bilirubin within normal limits, and at least a 15% reduction in ALP.
“Significantly more OCA-treated patients with cirrhosis achieved the primary composite endpoint compared to placebo,” Dr. Vierling and his coauthors wrote in a poster presented at the annual meeting for the American Association for the Study of Liver Diseases. The difference was individually significant for all three values that made up the composite primary endpoint as well.
Secondary endpoints included gamma-glutamyltransferase, alanine aminotrasferase, and aspartate aminotransferase, all of which were significantly reduced among patients taking OCA. Patients on placebo saw these values rise over the time period of the study.
There were no new safety signals seen in the post hoc analysis of the group with cirrhosis that were not seen in the trial at large, said Dr. Vierling. Two individuals in the subgroup dropped out of the trial because of pruritis, a similar proportion to that seen in the full trial population.
The drug’s manufacturer, Intercept Pharmaceuticals, is working with the Food and Drug Administration to establish appropriate doses and intervals for obeticholic acid so it may be used safely in individuals with decompensated cirrhosis, said Dr. Vierling.
Obeticholic acid, a farnesoid-X receptor agonist, is an approved agent to use as add-on therapy to ursodeoxycholic acid (UDCA), or as monotherapy for patients who can’t tolerate UDCA.
Dr. Vierling disclosed financial relationships with Intercept Pharmaceuticals and with several other pharmaceutical companies. The study was funded by Intercept Pharmaceuticals.