LAUSR

BACKGROUND AND AIMS The POISE randomized double-blind placebo-controlled trial demonstrated that obeticholic acid (OCA) reduced biomarkers associated with adverse clinical outcomes (ALP, bilirubin, AST, ALT) in patients with primary biliary cholangitis (PBC). The objective of this study was to evaluate time to first occurrence of liver transplant or death in OCA-treated patients in the POISE trial and open label extension versus comparable non-OCA-treated external controls. METHODS Propensity scores were generated for external control patients meeting POISE eligibility criteria from two registry studies (Global PBC and UK PBC) using an index date randomly selected between the first and last date (inclusive) on which eligibility criteria were met. Cox-proportional hazards models weighted by inverse probability of treatment assessed time to death or liver transplant. Additional analyses (Global PBC only) added hepatic decompensation to the composite endpoint, and assessed efficacy in patients with or without cirrhosis. RESULTS Over the 6-year follow-up, there were 5 deaths/liver transplants in 209 subjects in the POISE cohort (2.4%), 135/1381 patients in the Global PBC control (10.0%), and 281/2135 patients in the UK PBC control (13.2%). The hazard ratios (HR) for the primary outcome were 0.29 (95% CI 0.10, 0.83) for POISE vs Global PBC, and 0.30 (95% CI 0.12, 0.75) for POISE vs UK PBC. In Global PBC: HR=0.20 (95% CI 0.03, 1.22) for patients with cirrhosis, and HR=0.31 (95% CI 0.09, 1.04) without cirrhosis; HR was 0.42 (95% CI 0.21, 0.85) including hepatic decompensation. CONCLUSION Patients treated with OCA in a trial setting had significantly greater transplant-free survival than comparable external control patients.