Long‐Term Safety and Efficacy of Obeticholic Acid in Patients With Primary Biliary Cholangitis: Final Results of the POISE Long‐Term Safety Extension

BACKGROUND: Obeticholic acid (OCA) has been evaluated in patients with primary biliary cholangitis (PBC) with inadequate response or intolerance to ursodeoxycholic acid (UDCA) in the 12-month, double-blind, phase 3 POISE trial. A 3-year interim analysis of the open-label extension (OLE) demonstrated a favourable safety profile with sustained improvements in liver biochemistries. AIM: To present the final long-term safety and efficacy data from the 5-year POISE OLE. METHODS: All patients who entered the OLE (N = 193) were started on OCA 5 mg daily for a minimum of 3 months, after which the dose could be increased. Safety and efficacy were evaluated in the overall OLE population. Additional analyses censored data points following OCA titration > 10 mg to align with the prescribing label. RESULTS: POISE was terminated after it was determined that the OLE had achieved its study objectives of sustained efficacy with no unexpected safety findings. With censoring of data points following OCA titration to > 10 mg, the most common treatment-emergent adverse event (TEAE) was pruritus (70%); serious hepatic-related TEAEs were reported in five patients (3%). The serious hepatic-related TEAEs and deaths (n = 2, 1%) were assessed by the Investigators as unrelated to OCA. Liver biochemistries improved throughout the OLE; the response rate for the POISE primary endpoint was 63% at Month 72. Liver stiffness, as measured by transient elastography, was stable over the study duration. CONCLUSIONS: Findings from the POISE OLE support the safety and efficacy profile of long-term OCA treatment for patients with PBC with inadequate response or intolerance to UDCA (NCT01473524). TRIAL REGISTRATION: Phase 3 study of obeticholic acid in patients with primary biliary cirrhosis (POISE) ClinicalTrials.gov identifier: NCT01473524.