Hepatic real-world outcomes with obeticholic acid in primary biliary cholangitis (HEROES): A trial emulation study design.
| Title: | Hepatic real-world outcomes with obeticholic acid in primary biliary cholangitis (HEROES): A trial emulation study design. |
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| Authors: | Brookhart MA; Department of Population Health Sciences, Duke University, Durham, North Carolina, USA.; Target RWE, Durham, North Carolina, USA.; Mayne TJ; Intercept Pharmaceuticals, Morristown, New Jersey, USA.; Coombs C; Real World Evidence, Syneos Health, North Carolina, USA.; Breskin A; Target RWE, Durham, North Carolina, USA.; Ness E; Intercept Pharmaceuticals, Morristown, New Jersey, USA.; Bessonova L; Intercept Pharmaceuticals, Morristown, New Jersey, USA.; Chu YJ; Intercept Pharmaceuticals, Morristown, New Jersey, USA.; Li J; Intercept Pharmaceuticals, Morristown, New Jersey, USA.; Fried MW; Target RWE, Durham, North Carolina, USA.; Hansen BE; Department of Epidemiology and Biostatistics, Erasmus MC, Rotterdam, The Netherlands.; Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Ontario, Canada.; Toronto Centre for Liver Disease and TGHRI, University Health Network, Toronto, Ontario, Canada.; Kowdley KV; Liver Institute Northwest and Elson S. Floyd College of Medicine, Washington State University, Seattle, Washington, USA.; Jones D; Population Health Sciences Institute, Newcastle University, Newcastle upon Tyne, UK.; Mells G; Department of Hepatology, Cambridge Liver Unit, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK.; Academic Department of Medical Genetics, University of Cambridge, Cambridge, UK.; Trivedi PJ; Department of Immunology and Immunotherapy, National Institute for Health and Care Research (NIHR) Birmingham Biomedical Research Centre, Centre for Liver and Gastrointestinal Research, Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK.; Hiu S; Population Health Sciences Institute, Newcastle University, Newcastle upon Tyne, UK.; Kareithi DN; Population Health Sciences Institute, Newcastle University, Newcastle upon Tyne, UK.; Wason J; Population Health Sciences Institute, Newcastle University, Newcastle upon Tyne, UK.; Smith R; Department of Hepatology, Cambridge Liver Unit, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK.; Seeger JD; Optum Epidemiology, Boston, Massachusetts, USA.; Hirschfield GM; Toronto Centre for Liver Disease and TGHRI, University Health Network, Toronto, Ontario, Canada. |
| Source: | Hepatology (Baltimore, Md.) [Hepatology] 2025 Jun 01; Vol. 81 (6), pp. 1647-1659. Date of Electronic Publication: 2025 Jan 03. |
| Publication Type: | Journal Article; Pragmatic Clinical Trial |
| Language: | English |
| Journal Info: | Publisher: Wolters Kluwer Health, Inc Country of Publication: United States NLM ID: 8302946 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1527-3350 (Electronic) Linking ISSN: 02709139 NLM ISO Abbreviation: Hepatology Subsets: MEDLINE |
| Imprint Name(s): | Publication: 2023- : [Philadelphia] : Wolters Kluwer Health, Inc.; Original Publication: Baltimore, MD : Williams & Wilkins, [c1981]- |
| MeSH Terms: | Chenodeoxycholic Acid*/analogs & derivatives ; Chenodeoxycholic Acid*/therapeutic use ; Chenodeoxycholic Acid*/administration & dosage ; Cholagogues and Choleretics*/therapeutic use ; Liver Cirrhosis, Biliary*/drug therapy ; Liver Cirrhosis, Biliary*/mortality; Liver Transplantation/statistics & numerical data ; Ursodeoxycholic Acid/therapeutic use ; Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Treatment Outcome |
| Abstract: | Background and Aims: Primary biliary cholangitis is a rare, progressive liver disease. Obeticholic acid (OCA) received accelerated approval for treating patients with primary biliary cholangitis in whom ursodeoxycholic acid failed, based on a surrogate endpoint of reduction in ALP. Analysis of the long-term safety extension with 2 external control groups demonstrated a significant increase in event-free survival in OCA-treated patients. This fully real-world evidence study assessed the effect of OCA treatment on clinical outcomes.; Approach and Results: This trial emulation used data from the Komodo Healthcare Map claims database linked to US national laboratory, transplant, and death databases. Patients with compensated primary biliary cholangitis and intolerance/inadequate response to ursodeoxycholic acid who initiated OCA therapy were compared with patients who were OCA-eligible but not OCA-treated. The primary endpoint was time to the first occurrence of death, liver transplant, or hospitalization for hepatic decompensation, analyzed using a propensity-score weighted Cox proportional hazards model. Baseline prognostic factors were balanced using standardized morbidity ratio weighting. For the primary analysis, 4174 patients contributed 11,246 control index dates, and 403 patients contributed OCA indexes. Weighted groups were well balanced. Median (95% CI) follow-up in the OCA and non-OCA arms was 9.3 (8.4-10.6) months and 17.5 (16.2-18.6) months (weighted population; censored at discontinuation). Eight events occurred in the OCA arm and 32 in the weighted control (HR = 0.37; 95% CI = 0.14-0.75; p < 0.001). Effects were consistent for each component of the composite endpoint.; Conclusions: We identified a 63% reduced risk of hospitalization for hepatic decompensation, liver transplant, or death in OCA-treated versus non-OCA-treated individuals.; Trial Registration: HEROES; ClinicalTrials.gov NCT05292872.; (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.) |
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| Grant Information: | United Kingdom WT_ Wellcome Trust |
| Contributed Indexing: | Keywords: confirmatory trial; death; hepatic decompensation; liver disease; liver transplant |
| Molecular Sequence: | ClinicalTrials.gov NCT05292872 |
| Substance Nomenclature: | 0GEI24LG0J (Chenodeoxycholic Acid); 0 (Cholagogues and Choleretics); 0462Z4S4OZ (obeticholic acid); 724L30Y2QR (Ursodeoxycholic Acid) |
| Entry Date(s): | Date Created: 20241204 Date Completed: 20250519 Latest Revision: 20260127 |
| Update Code: | 20260130 |
| PubMed Central ID: | PMC12077331 |
| DOI: | 10.1097/HEP.0000000000001174 |
| PMID: | 39630028 |
| Database: | MEDLINE |
Journal Article; Pragmatic Clinical Trial