Among patients with primary biliary cholangitis (PBC), treatment with elafibranor improved predicted transplant-free survival rates based on improvements in GLOBE and UK-PBC scores, according to the phase III ELATIVE trial presented at The Liver Meeting 2024.

GLOBE and UK-PBC are validated prognostic scores that estimate the risk of liver transplant or death after 1 year of ursodeoxycholic acid (UDCA) therapy. [Gastroenterology 2015;149:1804-1812; Hepatology 2016;63:930-950]

The GLOBE and UK-PBC scores are based on alkaline phosphatase (ALP), total bilirubin, aspartate transaminase, alanine transaminase, albumin, and platelet levels.

This phase III trial included 161 patients (mean age 57 years, 96 percent female) with PBC who had an inadequate response or intolerance to UDCA. Participants were randomized in a 2:1 ratio to receive either elafibranor 80 mg once/day (n=108) or placebo (n=53) for 52 weeks. Baseline mean GLOBE and UK-PBC scores were -0.63 and -0.74, respectively, in the elafibranor group, and -0.73 and -0.80 in the placebo group. [The Liver Meeting 2024, abstract 0043]

After 1 year of treatment, the mean changes in GLOBE and UK-PBC scores were -0.36 and -0.27, respectively, for patients receiving elafibranor, and 0.13 and 0.05 for patients receiving placebo.

“Improvements in both scores were seen as early as week 4 and continued through 52 weeks of treatment with elafibranor, primarily due to a significant reduction in ALP,” said Dr Kris Kowdley from Liver Institute Northwest in Seattle, Washington, US.

Estimated transplant-free survival

“[The GLOBE and UK-PBC] prognostic scores were based on calculations from routine laboratory tests and clinical features, and they predict transplant-free survival for 10 or 15 years,” according to Kowdley.

Based on GLOBE scores at week 52, the median estimated transplant-free survival rates were higher among patients treated with elafibranor vs placebo at 10 (94.1 percent vs 92.6 percent) and 15 years (89.7 percent vs 87.2 percent).

UK-PBC scores at week 52 demonstrated a similar trend, with the elafibranor group achieving a higher median transplant-free survival rate than the placebo group (98.2 percent vs 97.4 percent [10 years] and 96.7 percent vs 95.1 percent [15 years]).

Furthermore, Kowdley noted that there was a positive impact on estimated transplant-free survival rates based on GLOBE scores at 10 and 15 years, regardless of the patient’s disease stage (early or advanced) or biochemical response (responders or nonresponders).

“Overall, patients treated with elafibranor had greater improvements in GLOBE and UK-PBC prognostic scores from baseline, suggesting significantly improved transplant-free survival, compared with placebo, … including in those with advanced disease and those who did not reach the threshold for biochemical response,” Kowdley concluded.