S0984 Long-Term Efficacy and Safety of Obeticholic Acid in Patients With Primary Biliary Cholangitis: A Demographic Subgroup Analysis of 5-Year Results From the POISE Trial

Abstract

INTRODUCTION: Primary biliary cholangitis (PBC) is a rare, progressive autoimmune liver disease that leads to fibrosis, cirrhosis, and liver transplantation. PBC primarily affects females, but male patients and those with earlier age at diagnosis are at high risk for disease progression. Obeticholic acid (OCA) is approved as second-line treatment of PBC in patients nonresponsive or intolerant to ursodeoxycholic acid. The efficacy and safety of 12-month OCA treatment in patients with PBC was previously demonstrated in the POISE trial.1 We report the long-term efficacy and safety of OCA for more than 5 years in demographic patient subgroups from the POISE trial. METHODS: POISE was a randomized, double-blind, placebo-controlled, 12-month, phase 3 trial evaluating the efficacy and safety of OCA 5–10 mg or 10 mg vs placebo in patients with PBC. This was followed by a 5-year open-label extension (OLE) study during which all patients received OCA. The current analysis evaluated efficacy and safety outcomes in patient subgroups based on sex (male vs female), median age at study entry (≤55 years vs > 55 years), and median age at diagnosis (≤47.5 years vs > 47.5 years). Assessments included changes from OCA baseline in clinical laboratory tests and adverse events (AEs). Paired t-tests assessed within group comparisons. RESULTS: A total of 193 patients were included in the OLE study (median exposure: 5.4 y). In the OLE analysis, significant decreases in mean alkaline phosphatase (ALP) values were observed from OCA baseline for each subgroup from month 3 through month 72 (Figure 1). Similar trends were observed for other key markers of cholestasis and hepatic damage in each subgroup (Table 1). AEs were consistent with previous OCA studies. Over the course of six years of study conduct, 69%–79% of patients reported a pruritus event. CONCLUSION: These findings provide additional information on OCA safety and efficacy in various demographic patient subgroups. Treatment with OCA resulted in improvements in ALP, ALT, AST, and GGT values in patients with PBC in all demographic subgroups assessed. In the OLE, improvements in ALP were achieved by 3 months after OCA treatment initiation and were sustained after 5 years; these are important findings given the progressive nature of the disease.Figure 1Table 1