PTU-100 Efficacy of obeticholic acid treatment in patients with primary biliary cholangitis with cirrhosis

Introduction Obeticholic acid (OCA) is a potent and selective farnesoid X receptor (FXR) agonist under investigation for treatment of primary biliary cholangitis (PBC) and other chronic liver diseases. POISE was a double-blind, placebo-controlled, randomised Phase 3 study examining the efficacy of OCA in PBC. The objective of this post-hoc analysis was to assess the efficacy of OCA in the subset of patients with cirrhosis who were at higher risk of progression to liver-related outcomes or death. Method We randomised and dosed 216 patients 1:1:1 with placebo (PBO) (n=73), OCA 5–10 mg (n=70, titrated to 10 mg after 6 months based on response and tolerability) or OCA 10 mg (n=73). Inclusion criteria included PBC diagnosis, ALP≥1.67x ULN and/or total bilirubin (BILI) >ULN to Results Cirrhosis was present in approximately 17% of patients in POISE: PBO, n=13; OCA 5–10 mg, n=13; OCA 10 mg, n=10. At month 12, 54% (p Conclusion In this post-hoc analysis, no additional safety concerns due to OCA were observed in the subgroup of OCA-treated patients with cirrhosis, and OCA treatment resulted in significant improvements in biochemical markers associated with disease progression. The percentage of patients achieving the primary composite endpoint on OCA was comparable in patients with cirrhosis and non-cirrhotic patients. These results suggest that OCA may play a beneficial role in preservation of the functional capacity of residual liver tissue in cirrhotic patients. Disclosure of Interest J Vierling: None Declared, G. Hirschfield: None Declared, D. Jones: None Declared, R. Groszmann: None Declared, K. Kowdley: None Declared, R. Pencek Conflict with: Intercept Pharmaceuticals, Inc., Conflict with: Intercept Pharmaceuticals, Inc., T. Marmon Conflict with: Intercept Pharmaceuticals, Inc., Conflict with: Intercept Pharmaceuticals, Inc., L. MacConell Conflict with: Intercept Pharmaceuticals, Inc., Conflict with: Intercept Pharmaceuticals, Inc.