Baseline Alkaline Phosphatase Impacts Response Rates in Primary Biliary Cholangitis: Exploring Response to Elafibranor in <scp>ELATIVE</scp>

BACKGROUND & AIMS: Baseline alkaline phosphatase (ALP) levels can influence the likelihood of achieving dichotomous biochemical response criteria in primary biliary cholangitis (PBC). This concept was explored using Week 52 data from the phase III ELATIVE trial (NCT04526665), which assessed elafibranor, a peroxisome proliferator-activated receptor α/δ agonist approved as a second-line treatment for PBC. METHODS: Patients were grouped by baseline ALP. Outcomes assessed: biochemical response, ALP normalization, ALP change from baseline (CfB), transplant-free survival (using GLOBE score). RESULTS: At Week 52, biochemical response was achieved across all subgroups receiving elafibranor (≤ 2× upper limit of normal [ULN]: 86.7%, > 2-≤ 2.5× ULN: 80.0%, > 2.5-≤ 3× ULN: 52.0%, > 3-≤ 4× ULN: 22.2%, > 4× ULN: 18.8%), and one subgroup receiving placebo (≤ 2× ULN: 13.3%). ALP normalization occurred only with elafibranor (≤ 2× ULN: 53.3%, > 2-≤ 2.5× ULN: 12.0%, > 2.5-≤ 3× ULN: 12.0%, > 4× ULN: 12.5%). Mean ALP reductions were consistent across subgroups receiving elafibranor (overall CfB: -38.9%). Patients receiving elafibranor, regardless of biochemical response, had similar reductions in risk of liver transplant and/or liver-related mortality within 15 years (-4.0% to -4.5%); among patients receiving placebo, reduced risk was only predicted in responders (-1.5%). CONCLUSIONS: In ELATIVE, lower baseline ALP correlated with higher biochemical response and ALP normalization rates with elafibranor. However, among patients receiving elafibranor, relative reductions in risk scores and ALP were consistent regardless of biochemical response and pre-treatment ALP, indicating treatment benefit. Similar biochemical benefits were not observed among patients receiving placebo. These results support evaluating continuous measures and prognostic scores alongside dichotomous criteria to comprehensively assess efficacy. TRIAL REGISTRATION: NCT04526665.