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Greater Transplant-Free Survival in Patients Receiving Obeticholic Acid for Primary Biliary Cholangitis in a Clinical Trial Setting Compared to Real-World External Controls

2022; Elsevier BV; Volume: 163; Issue: 6 Linguagem: Inglês

10.1053/j.gastro.2022.08.054

1528-0012

Carla Fiorella Murillo Perez, Holly Fisher, Shaun Hiu, Dorcas Kareithi, Femi Adekunle, Tracy J. Mayne, Elizabeth Smoot Malecha, Erik C. Ness, Adriaan J. van der Meer, Willem J. Lammers, Palak Trivedi, Pier Maria Battezzati, Frederik Nevens, Kris V. Kowdley, Tony Bruns, Nora Cazzagon, Annarosa Floreani, Andrew L. Mason, Albert Parés, María‐Carlota Londoño, Pietro Invernizzi, Marco Carbone, Ana Lleò, Marlyn J. Mayo, George Ν. 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 G. Healey, Anton Gunasekera, Yiannis Kallis, Gavin Wright, Thiriloganathan Mathialahan, Richard J. Evans, Jaber Gasem, David Ramanaden, Emma Ward, Mahesh Bhalme, Paul Southern, James L. 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, G. W. G. Bird, Martin Prince, Geeta Prasad, Paul Kitchen, John Hutchinson, Prakash C. Gupta, David Jones, Amir Shah, Subrata Saha, Katharine Pollock, Stephen Barclay, Natasha McDonald, Simon Rushbrook, Robert Przemioslo, Andrew J. Millar, S. C. Mitchell, A. M. Davis, Asifabbas Naqvi, Tom Lee, Stephen Ryder, Jane Collier, Matthew Cramp, Richard Aspinal, Jonathan Booth, Earl G. Williams, Hyder Hussaini, John M. 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 R. Shearman, Gary Bray, Michael S. Roberts, Daniel Forton, Nik 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 D. Austin, Altaf Palegwala, Vishwaraj Vemala, Andrew Higham, Jocelyn Fraser, Andrew A. Li, S. Ramakrishnan, Alistair King, Simon Whalley, Ian Gee, Richard Keld, Helen Fellows, James Gotto, Charles Millson,

Gallbladder and Bile Duct Disorders

Background & AimsThe 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.MethodsPropensity 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.ResultsDuring 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.ConclusionsPatients treated with OCA in a trial setting had significantly greater transplant-free survival than comparable external control patients. 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. 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. 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. Patients treated with OCA in a trial setting had significantly greater transplant-free survival than comparable external control patients.