TOPLINE:

Biochemical non-response to obeticholic acid as a second-line therapy predicted a heightened risk for clinical events in patients with primary biliary cholangitis (PBC). Although response rates to obeticholic acid improved over time, more than 40% of patients discontinued the treatment within 4 years.

METHODOLOGY:

• In a multicentre study, researchers analysed data of 336 patients with PBC who initiated obeticholic acid as a second-line treatment between August 2017 and 2019 (median age at treatment initiation, 53 years; 89% women), with follow-up continuing until June 2024.
• They assessed whether biochemical response to obeticholic acid therapy can predict the development of clinical events.
• Biochemical response was defined as an alkaline phosphatase (ALP) value < 1.67× the upper limit of normal with a ≥ 15% reduction from baseline and normal total serum bilirubin values.
• Clinical events were defined as the development of hepatic decompensation (ascites, hepatic encephalopathy, or variceal bleeding), hepatocellular carcinoma, referral for liver transplant assessment, or death from any cause.

TAKEAWAY:

• Among the 336 patients, 150 (45%) discontinued obeticholic acid over 48 months of follow-up; 77% of patients who experienced a clinical event discontinued the treatment.
• Median ALP values declined from 2.69× the upper limit of normal at baseline to 1.96×, 1.60×, 1.50×, and 1.38× the upper limit of normal at 12, 24, 36, and 48 months, respectively (P < .001 for all), with median percentage reductions in serum ALP levels of 27%, 41%, 44%, and 55% at these respective timepoints.
• Biochemical response rates were 37% at 12 months, 48% at 24 months, 63% at 36 months, and 55% at 48 months, with normal ALP values achieved in 7%, 14%, 25%, and 19% of patients at these respective timepoints.
• Biochemical non-response at 12 months (adjusted hazard ratio [aHR], 3.29; P = .012) and cirrhosis at baseline (aHR, 19.67; P < .001) were significant predictors of clinical events.

IN PRACTICE:

"Our data add to this growing body of evidence, by validating the prognostic utility of biochemical response criteria in a large OCA [obeticholic acid]-treated cohort, independently of cirrhosis, and with clinical event capture for more than 4 years post treatment initiation," the authors wrote.

SOURCE:

This study was led by Nadir Abbas, National Institute for Health and Care Research Birmingham Biomedical Research Centre, Centre for Liver and Gastrointestinal Research, University of Birmingham, Birmingham, England. It was published online on September 22, 2025, in Alimentary Pharmacology and Therapeutics.

LIMITATIONS:

Differences in clinical practice — particularly transplant access and the management of difficult-to-treat pruritus — were likely to occur. The comparison of combination vs switch therapy relied only on UK cohort data.

DISCLOSURES:

This study was supported by the National Institute for Health and Social Care Research, Biomedical Research Centre. Several authors reported receiving institutional salary support, grant support, speaker fees, consulting fees, and/or advisory board fees from various pharmaceutical companies and institutes.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.