Author information

Affiliations

• ¹Toronto Centre for Liver Disease, Toronto General Hospital, University of Toronto, Toronto, Ontario, Canada.
• ²Newcastle University, Newcastle upon Tyne, United Kingdom.
• ³Intercept Pharmaceuticals, Morristown, New Jersey.
• ⁴Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center Rotterdam, Rotterdam, the Netherlands.
• ⁵University of Birmingham, Birmingham, United Kingdom.
• ⁶Università degli Studi di Milano, Milan, Italy.
• ⁷University Hospital Katholieke Universiteit Leuven, Leuven, Belgium.
• ⁸Liver Institute Northwest, Seattle, Washington.
• ⁹Department of Gastroenterology and Hepatology, University Hospital Rheinisch-Westfälische Technische Hochschule Aachen University, Aachen, Germany.
• ¹⁰University of Padova, Padova, Italy.
• ¹¹Department of Medicine, University of Alberta, Edmonton, Alberta, Canada.
• ¹²Department of Medicine, Liver Unit, Hospital Clínic, University of Barcelona, The August Pi i Sunyer Biomedical Research Institute, Biomedical Research Networking Center in Hepatic and Digestive Diseases, Barcelona, Spain; European Reference Network on Hepatological Diseases, Barcelona, Spain.
• ¹³European Reference Network on Hepatological Diseases, Barcelona, Spain; Division of Gastroenterology, Center for Autoimmune Liver Diseases, Department of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy; San Gerardo Hospital, Monza, Italy.
• ¹⁴University of Milano-Bicocca, Monza, Italy.
• ¹⁵Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy; IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy.
• ¹⁶Department of Medicine, Division of Digestive and Liver Disease, University of Texas, Southwestern Medical Center, Dallas, Texas.
• ¹⁷European Reference Network on Hepatological Diseases, Barcelona, Spain; Department of Medicine and Research Laboratory of Internal Medicine, National Expertise Center of Greece in Autoimmune Liver Diseases, General University Hospital of Larissa, Larissa, Greece.
• ¹⁸Royal Free London National Health Service Foundation Trust, London, United Kingdom.
• ¹⁹Department of Hepatology, Ghent University Hospital, Ghent, Belgium.
• ²⁰Toronto Centre for Liver Disease, Toronto General Hospital, University of Toronto, Toronto, Ontario, Canada; Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center Rotterdam, Rotterdam, the Netherlands.
• ²¹Cambridge Liver Unit, Cambridge University Hospitals National Health Service Foundation Trust, Cambridge, United Kingdom.
• ²²Academic Department of Medical Genetics, University of Cambridge, Cambridge, United Kingdom.
• ²³Medical University of Vienna, Vienna, Austria.
• ²⁴University of California Davis, Sacramento, California.
• ²⁵Mayo Clinic, Scottsdale, Arizona.
• ²⁶Saint-Antoine University Hospital, Paris, France.
• ²⁷Addenbrooke's Hospital, Cambridge, United Kingdom.
• ²⁸Department of Biostatistics, Newcastle University, Newcastle upon Tyne, United Kingdom.
• ²⁹Toronto Centre for Liver Disease, Toronto General Hospital, University of Toronto, Toronto, Ontario, Canada; Department of Epidemiology & Biostatistics, Erasmus MC, Rotterdam, the Netherlands, Toronto, Ontario, Canada; IHPME, University of Toronto, Toronto, Ontario, Canada. Electronic address: b.hansen@erasmusmc.nl.

Abstract

Background & aims: The Primary Biliary Cholangitis (PBC) Obeticholic Acid (OCA) International Study of Efficacy (POISE) randomized, double-blind, placebo-controlled trial demonstrated that OCA reduced biomarkers associated with adverse clinical outcomes (ie, alkaline phosphatase, bilirubin, aspartate aminotransferase, and alanine aminotransferase) in patients with PBC. The objective of this study was to evaluate time to first occurrence of liver transplantation or death in patients with OCA in the POISE trial and open-label extension vs comparable non-OCA-treated external controls.

Methods: Propensity scores were generated for external control patients meeting POISE eligibility criteria from 2 registry studies (Global PBC and UK-PBC) using an index date selected randomly 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 transplantation. Additional analyses (Global PBC only) added hepatic decompensation to the composite end point and assessed efficacy in patients with or without cirrhosis.

Results: During the 6-year follow-up, there were 5 deaths or liver transplantations in 209 subjects in the POISE cohort (2.4%), 135 of 1381 patients in the Global PBC control (10.0%), and 281 of 2135 patients in the UK-PBC control (13.2%). The hazard ratios (HRs) 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 the Global PBC study, HR was 0.20 (95% CI, 0.03-1.22) for patients with cirrhosis and 0.31 (95% CI, 0.09-1.04) for those without cirrhosis; HR was 0.42 (95% CI, 0.21-0.85) including hepatic decompensation.

Conclusions: Patients treated with OCA in a trial setting had significantly greater transplant-free survival than comparable external control patients.