Baseline Alkaline Phosphatase Impacts Response Rates in Primary Biliary Cholangitis: Exploring Response to...

Area of Science:

• Hepatology
• Clinical Trials
• Pharmacology

Background:

• Baseline alkaline phosphatase (ALP) levels are known to impact treatment outcomes in primary biliary cholangitis (PBC).
• The phase III ELATIVE trial evaluated elafibranor, a PPARα/δ agonist, as a second-line PBC treatment.
• This analysis specifically investigated the influence of baseline ALP on treatment response to elafibranor.

Purpose of the Study:

• To explore the relationship between baseline alkaline phosphatase (ALP) levels and treatment response in primary biliary cholangitis (PBC) patients.
• To assess the efficacy of elafibranor in achieving biochemical response and normalization of ALP across different baseline ALP strata.
• To evaluate the impact of elafibranor on transplant-free survival and risk of liver-related mortality in relation to baseline ALP.

Main Methods:

• Patients from the ELATIVE trial (NCT04526665) were stratified based on baseline ALP levels.
• Key outcomes included biochemical response, ALP normalization, ALP change from baseline (CfB), and transplant-free survival (GLOBE score).
• Week 52 data from elafibranor and placebo arms were analyzed.

Main Results:

• Elafibranor demonstrated biochemical response across all baseline ALP subgroups, with rates ranging from 18.8% to 86.7%.
• ALP normalization and significant ALP reductions (mean CfB: -38.9%) were observed with elafibranor, irrespective of baseline ALP.
• Elafibranor treatment led to consistent risk reductions for liver transplant and/or mortality, regardless of baseline ALP or biochemical response.

Conclusions:

• While lower baseline ALP correlated with higher response rates to elafibranor, the treatment benefit was consistent across all strata.
• Elafibranor demonstrated efficacy in improving biochemical markers and reducing long-term liver disease risk in PBC patients.
• The study supports using continuous measures and prognostic scores, in addition to dichotomous criteria, for comprehensive efficacy assessment.