Greater Transplant-Free Survival in Patients Receiving Obeticholic Acid for Primary Biliary Cholangitis in a Clinical Trial Setting Compared to Real-World External Controls
Year: 2022
Type: article
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.
Source: Gastroenterology
Authors: C. Fiorella Murillo Perez, Holly Fisher, Shaun Hiu, Dorcas Kareithi, Femi Adekunle, Tracy Mayne, Elizabeth Malecha, Erik Ness, Adriaan J. van der Meer, Willem J. Lammers, Palak J. Trivedi, Pier Maria Battezzati, Frederik Nevens, Kris V. Kowdley, Tony Bruns, Nora Cazzagon, Annarosa Floreani, Andrew L. Mason, Albert Parés, Maria-Carlota Londoño, Pietro Invernizzi, Marco Carbone, Ana Lleo, Marlyn J. Mayo, George N. Dalekos, Nikolaos K. Gatselis, Douglas Thorburn, Xavier Verhelst, Aliya Gulamhusein, Harry L.A. Janssen, Rachel Smith, Steve Flack, Victoria Mulcahy, Michael Trauner, Christopher L. Bowlus, Keith D. Lindor, Christophe Corpechot, David Jones, George Mells, Gideon M. Hirschfield, James Wason, Bettina E. Hansen, Richard Sturgess, Christopher Healey, Anton Gunasekera, Yiannis Kallis, Gavin Wright, Thiriloganathan Mathialahan, Richard Evans, Jaber Gasem, David Ramanaden, Emma Ward, Mahesh Bhalme, Paul Southern, James Maggs, Mohamed Yousif, George Mells, Brijesh Srivastava, Matthew Foxton, Carole Collins, Yash Prasad, Francisco Porras-Perez, Tom Yapp, Minesh Patel, Roland Ede, Martyn Carte, Konrad Koss, Prayman Sattianayagam, Charles Grimley, Jude Tidbury, Dina Mansour, Matilda Beckley, Coral Hollywood, John Ramag, Harriet Gordon, Joanne Ridpath, Bob Grover, George Abouda, Ian Rees, Mark Narain, Imroz Salam, Paul Banim, Debasish Das, Helen Matthews, Faiyaz Mohammed, Rebecca Jones, Sambit Sen, George Bird, Martin Prince, Geeta Prasad, Paul Kitchen, John Hutchinson, Prakash Gupta, David Jones, Amir Shah, Subrata Saha, Katharine Pollock, Stephen Barclay, Natasha McDonald, Simon Rushbrook, Robert Przemioslo, Andrew Millar, Steven Mitchell, Andrew Davis, Asifabbas Naqvi, Tom Lee, Stephen Ryder, Jane Collier, Matthew Cramp, Richard Aspinal, Jonathan Booth, Earl Williams, Hyder Hussaini, John Christie, Tehreem Chaudhry, Douglas Thorburn, Stephen Mann, Aftab Ala, Julia Maltby, Chris Corbett, Saket Singhal, Barbara Hoeroldt, Jeff Butterworth, Andrew Douglas, Rohit Sinha, Simon Panter, Jeremy Shearman, Gary Bray, Michael Roberts, Daniel Forton, Nicola Taylor, Wisam Jafar, Matthew Cowan, Chin Lye Ch'ng, Mesbah Rahman, Emma Wesley, Sanjiv Jain, Aditya Mandal, Mark Wright, Palak Trivedi, Fiona Gordon, Esther Unitt, Andrew Austin, Altaf Palegwala, Vishwaraj Vemala, Andrew Higham, Jocelyn Fraser, Andy Li, Subramaniam Ramakrishnan, Alistair King, Simon Whalley, Ian Gee, Richard Keld, Helen Fellows, James Gotto, Charles Millson
Institutions: University of Toronto, Toronto General Hospital, Newcastle University, Intercept Pharmaceuticals (United States), Erasmus MC, University of Birmingham, University of Milan, KU Leuven, Liver Institute Northwest, Universitätsklinikum Aachen, RWTH Aachen University, University of Padua, University of Alberta, Hospital Clínic de Barcelona, Universitat de Barcelona, Azienda Ospedaliera San Gerardo, University of Milano-Bicocca, Humanitas University, IRCCS Humanitas Research Hospital, The University of Texas Southwestern Medical Center, University Hospital of Larissa, General Hospital of Larisa, Greece, National Health Service, Royal Free London NHS Foundation Trust, The Royal Free Hospital, Ghent University Hospital, Cambridge University Hospitals NHS Foundation Trust, University of Cambridge, Medical University of Vienna, University of California, Davis, Mayo Clinic in Arizona, Hôpital Saint-Antoine, Addenbrooke's Hospital, Airedale NHS Foundation Trust
Language: English
Topic: Liver Diseases and Immunity
Subfield: Hepatology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $3,200
Funders: Middlesex University, University Hospital Southampton NHS Foundation Trust, NHS Greater Glasgow and Clyde, King's College Hospital NHS Foundation Trust, Nottingham University Hospitals NHS Trust, University Hospitals Bristol NHS Foundation Trust, University Hospitals of Leicester NHS Trust, Betsi Cadwaladr University Health Board, University Hospitals Birmingham NHS Foundation Trust, Royal Free London NHS Foundation Trust, Swansea Bay University Health Board, University Hospitals Plymouth NHS Trust, Intercept Pharmaceuticals, National Institute for Health and Care Research, University of Cambridge, King's College London, University of Oxford, Chelsea and Westminster Hospital NHS Foundation Trust, University of Nottingham, Cambridge University Hospitals, Newcastle upon Tyne Hospitals NHS Foundation Trust, North Bristol NHS Trust, Oxford University Hospitals NHS Foundation Trust, St George's University Hospitals NHS Foundation Trust, Sheffield Teaching Hospitals NHS Foundation Trust, Barts Health NHS Trust, Liverpool University Hospitals NHS Foundation Trust, University Hospitals Coventry and Warwickshire NHS Trust, Medical Research Council
OpenAlex ID: W4296777654