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

Humans Ursodeoxycholic Acid / adverse effects Liver Cirrhosis, Biliary / diagnosis Chenodeoxycholic Acid / adverse effects Liver Cirrhosis / complications

Global PBC Obeticholic Acid Propensity Score Transplant-Free Survival UK-PBC

Journal

Gastroenterology

ISSN: 1528-0012

Titre abrégé: Gastroenterology

Pays: United States

ID NLM: 0374630

Informations de publication

Date de publication:
12 2022

Historique:

received: 04 03 2022

revised: 19 07 2022

accepted: 30 08 2022

pubmed: 24 9 2022

medline: 23 11 2022

entrez: 23 9 2022

Statut: ppublish

Résumé

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.

Sections du résumé

BACKGROUND & AIMS

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.

Identifiants

DOI: 10.1053/j.gastro.2022.08.054 PMID: 36150526

pubmed: 36150526

pii: S0016-5085(22)01060-5

doi: 10.1053/j.gastro.2022.08.054

pii:

doi:

Substances chimiques

obeticholic acid 0462Z4S4OZ

Ursodeoxycholic Acid 724L30Y2QR

Chenodeoxycholic Acid 0GEI24LG0J

Types de publication

Randomized Controlled Trial Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

Pagination

1630-1642.e3

Subventions

Organisme : Medical Research Council

ID : MR/L001489/1

Pays : United Kingdom

Investigateurs

Richard Sturgess (R)

Christopher Healey (C)

Anton Gunasekera (A)

Yiannis Kallis (Y)

Gavin Wright (G)

Thiriloganathan Mathialahan (T)

Richard Evans (R)

Jaber Gasem (J)

David Ramanaden (D)

Emma Ward (E)

Mahesh Bhalme (M)

Paul Southern (P)

James Maggs (J)

Mohamed Yousif (M)

George Mells (G)

Brijesh Srivastava (B)

Matthew Foxton (M)

Carole Collins (C)

Yash Prasad (Y)

Francisco Porras-Perez (F)

Tom Yapp (T)

Minesh Patel (M)

Roland Ede (R)

Martyn Carte (M)

Konrad Koss (K)

Prayman Sattianayagam (P)

Charles Grimley (C)

Jude Tidbury (J)

Dina Mansour (D)

Matilda Beckley (M)

Coral Hollywood (C)

John Ramag (J)

Harriet Gordon (H)

Joanne Ridpath (J)

Bob Grover (B)

George Abouda (G)

Ian Rees (I)

Mark Narain (M)

Imroz Salam (I)

Paul Banim (P)

Debasish Das (D)

Helen Matthews (H)

Faiyaz Mohammed (F)

Rebecca Jones (R)

Sambit Sen (S)

George Bird (G)

Martin Prince (M)

Geeta Prasad (G)

Paul Kitchen (P)

John Hutchinson (J)

Prakash Gupta (P)

David Jones (D)

Amir Shah (A)

Subrata Saha (S)

Katharine Pollock (K)

Stephen Barclay (S)

Natasha McDonald (N)

Simon Rushbrook (S)

Robert Przemioslo (R)

Andrew Millar (A)

Steven Mitchell (S)

Andrew Davis (A)

Asifabbas Naqvi (A)

Tom Lee (T)

Stephen Ryder (S)

Jane Collier (J)

Matthew Cramp (M)

Richard Aspinal (R)

Jonathan Booth (J)

Earl Williams (E)

Hyder Hussaini (H)

John Christie (J)

Tehreem Chaudhry (T)

Douglas Thorburn (D)

Stephen Mann (S)

Aftab Ala (A)

Julia Maltby (J)

Chris Corbett (C)

Saket Singhal (S)

Barbara Hoeroldt (B)

Jeff Butterworth (J)

Andrew Douglas (A)

Rohit Sinha (R)

Simon Panter (S)

Jeremy Shearman (J)

Gary Bray (G)

Michael Roberts (M)

Daniel Forton (D)

Nicola Taylor (N)

Wisam Jafar (W)

Matthew Cowan (M)

Chin Lye Ch'ng (CL)

Mesbah Rahman (M)

Emma Wesley (E)

Sanjiv Jain (S)

Aditya Mandal (A)

Mark Wright (M)

Palak Trivedi (P)

Fiona Gordon (F)

Esther Unitt (E)

Andrew Austin (A)

Altaf Palegwala (A)

Vishwaraj Vemala (V)

Andrew Higham (A)

Jocelyn Fraser (J)

Andy Li (A)

Subramaniam Ramakrishnan (S)

Alistair King (A)

Simon Whalley (S)

Ian Gee (I)

Richard Keld (R)

Helen Fellows (H)

James Gotto (J)

Charles Millson (C)

Commentaires et corrections

Type : CommentIn