| Title: |
Hepatic real-world outcomes with obeticholic acid in primary biliary cholangitis (HEROES): a trial emulation study design |
| Authors: |
Brookhart MA; Mayne TJ; Coombs C; Breskin A; Ness E; Bessonova L; Chu YJ; Li J; Fried MW; Hansen BE; Kowdley KV; Jones D; Mells G; Trivedi PJ; Hiu S; Kareithi DN; Wason J; Smith R; Seeger JD; Hirschfield GM |
| Source: |
Hepatology, 2024 |
| Publisher Information: |
Lippincott Williams and Wilkins |
| Publication Year: |
2024 |
| Collection: |
Newcastle University Library ePrints Service |
| Description: |
© 2024 The Author(s). Background and aims: Primary biliary cholangitis (PBC) is a rare, progressive liver disease. Obeticholic acid (OCA) received accelerated approval for treating patients with PBC in whom ursodeoxycholic acid (UDCA) failed, based on a surrogate endpoint of reduction in alkaline phosphatase. 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 the 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 PBC and intolerance/inadequate response to UDCA who initiated OCA therapy were compared with patients who were OCA-eligible but not OCA-treated. The primary endpoint was time to 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; 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, 32 in the weighted control (HR=0.37; 95% CI=0.14–0.75; p |
| Document Type: |
article in journal/newspaper |
| File Description: |
application/pdf |
| Language: |
unknown |
| Relation: |
https://eprints.ncl.ac.uk/303271; https://eprints.ncl.ac.uk/fulltext.aspx?url=303271/8B3E79C9-6C31-4BEE-B583-2DF278C078E4.pdf&pub_id=303271 |
| Availability: |
https://eprints.ncl.ac.uk/303271 |
| Rights: |
https://creativecommons.org/licenses/by-nc-nd/4.0/ |
| Accession Number: |
edsbas.BB51E011 |
| Database: |
BASE |