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Patients with primary biliary cholangitis (PBC) on obeticholic acid (Ocaliva) had better transplant-free survival compared with those who did not receive the treatment, according to an analysis using participants from the randomized POISE trial.

Over 6 years of follow-up, fewer deaths and liver transplants occurred in 209 patients in the POISE cohort (2.4%) compared with external control patients who did not receive obeticholic acid in two registry cohorts, reported Bettina Hansen, PhD, of the Erasmus University Medical Center in Rotterdam, the Netherlands, and colleagues:

• 10% of 1,381 patients in the Global PBC control group
• 13.2% of 2,135 patients in the U.K. PBC control group

The prespecified primary analysis using inverse probability treatment weighting yielded hazard ratios of 0.29 (95% CI 0.10-0.83, P=0.02) for POISE patients versus Global PBC controls, and 0.30 (95% CI 0.12-0.75, P<0.01) for POISE patients versus U.K. PBC controls, indicating that those treated with obeticholic acid in a trial setting had significantly greater transplant-free survival than those in the external control groups, the authors noted in .

"The goal of therapy in patients with PBC is to prevent progression to these events, and this is the first study to demonstrate that treatment with obeticholic acid is associated with a reduction in death, liver transplant, and hepatic decompensation," they wrote. "These data add to an accumulating body of real-world evidence showing a positive effect of OCA [obeticholic acid] treatment on hepatic biomarkers, fibrosis, and PBC risk scores, and support current guidance, which recommend initiation of second-line therapy if UDCA [ursodeoxycholic acid] is not tolerated or at 6 to 12 months after starting UDCA if there is an inadequate response."

PBC, a rare autoimmune cholestatic liver disease, causes progressive destruction of the intrahepatic bile ducts, resulting in cholestasis, inflammation, and fibrosis. Without treatment, patients can progress to end-stage cirrhosis, leading to hepatic decompensation and, without transplantation, death. PBC predominantly affects women over 40.

Obeticholic acid works to reduce liver enzymes, such as alkaline phosphatase (ALP), which are known to cause adverse liver outcomes. It was approved in 2016 as a second-line treatment option for PBC patients who show an intolerance or inadequate response to first-line UDCA, but in 2021, the FDA restricted the use of obeticholic acid due to the risk of serious liver injury in patients with advanced cirrhosis.

"The results of this analysis support the continued use of long-term OCA therapy to optimize the prognosis of patients with PBC, as well as the use of surrogate markers to accelerate drug approval in rare disease," Hansen and colleagues concluded.

Sean Koppe, MD, of Northwestern Medicine in Chicago, told 番茄社区 that "obeticholic acid was previously shown to , and the hope was that this would translate into improved long-term outcomes."

"The current study, which is based on a longer follow-up period of 6 years, confirms these hopes that patients on obeticholic acid would have a reduced mortality and/or need for liver transplant," said Koppe, who was not involved in the study.

For this study, Hansen and colleagues examined data on PBC patients receiving obeticholic acid from the multicenter, double-blind, placebo-controlled (n=209), including 193 patients who rolled over into its open-label extension trial, and compared them with PBC patients who did not receive obeticholic acid from two registry studies, (n=1,381) and (n=2,135). All included patients were inadequate responders to UDCA.

Patients with events occurring during the first 6 months were excluded. However, an ad hoc sensitivity analysis showed that the findings remained significant and did not differ even when including events that occurred within the first 6 months.

Mean patient age was 56-61. Nearly all were women (89-91%). Most had taken UDCA for an average of 40-48 months. Average disease duration was 4.5 to 7.8 years.

A subgroup analysis showed no significant difference between POISE patients with or without cirrhosis compared with the Global PBC cohort.

Changes in biomarker levels -- from baseline to 1 year -- favored both control groups, except for bilirubin in the U.K. PBC cohort.

Hansen and colleagues noted that unobserved bias and selection bias could not be ruled out, since the POISE trial may have enrolled healthier patients.

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