Patients with PBC who failed with obeticholic acid may still achieve ‘some benefit’
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Key takeaways:
- Incomplete responders to obeticholic acid had significant increases from baseline in fibroblast growth factor 19 vs. those on placebo.
- They also had lower fibrosis scores and reductions in inflammatory markers.
SAN DIEGO — Patients with primary biliary cholangitis who were incomplete responders to obeticholic acid may still demonstrate improvement in inflammatory markers and fibrosis scores, according to research presented at The Liver Meeting.
During his presentation, David W. Victor III, MD, associate professor of clinical medicine at Houston Methodist Hospital, noted the findings show “that there may be some benefit in those who do not respond for the benefit of second-line therapy, in terms of lower inflammation and perhaps a reduction in fibrosis progression.”
In a retrospective review of the phase 3 POISE study, Victor and colleagues evaluated the effect of obeticholic acid among patients with primary biliary cholangitis who were incomplete responders, defined as not meeting the composite endpoint (alkaline phosphatase < 1.67-times the upper limit of normal [ULN] with 15% reduction from baseline and total bilirubin ULN) at 12 months.
In the study, 216 patients who had inadequate response or intolerance to ursodeoxycholic acid were randomly assigned to obeticholic acid 5 mg titration (n = 70), obeticholic acid 10 mg (n = 73) or placebo (n = 73). At 6 months, patients in the 5 mg group remained at this dose or were up-titrated to 10 mg through 12 months, depending on their response and tolerability to treatment.
At baseline and 6 and 12 months, the researchers assessed fibroblast growth factor 19 (FGF19), C-reactive protein, immunoglobin M (IgM) and cleaved cytokeratin-18 (CK-18), as well as Fibrosis-4 (FIB-4) scores.
Results at 12 months showed that the median percentage change from baseline in FGF19 was significantly increased in both the titration (52%) and 10 mg (94%) groups compared with placebo.
“Incomplete responders to [obeticholic acid] had higher levels of FGF19 as a marker associated with [farnesoid X receptor] activation,” Victor said. “This has been shown to improve downregulation of bile acid production and prevent further damage to small bile ducts.”
In addition, significant reductions from baseline were observed in the titration and 10 mg groups in CRP (–31% and –32%) and IgM (–13% and –18%), as well as in CK-18 at both 6 months (–30% and –36%) and 12 months (–26% and –37%). A significant reduction in FIB-4 occurred only in the up-titrated group at 12 months.
“Incomplete responders had reduced levels of immune-mediated inflammatory markers CRP, CK-18 and IgM, which are prognostic markers for worsening disease,” Victor told attendees. “And there was a trend towards lower fibrosis scores.”
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Victor DW, et al. The effect of obeticholic acid on inflammatory markers and fibrosis scores in POISE incomplete responders: A retrospective review of POISE, a phase 3 trial of obeticholic acid for the treatment of primary biliary cholangitis. Presented at: The Liver Meeting; Nov. 15-19, 2024; San Diego (hybrid meeting).
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