Browse by author
Lookup NU author(s): Shaun Hiu, Dorcas KareithiORCiD, Professor James WasonORCiD
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND).
© 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<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.
Author(s): 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
Publication type: Article
Publication status: Published
Journal: Hepatology
Year: 2024
Pages: Epub ahead of print
Online publication date: 02/12/2024
Acceptance date: 02/04/2018
Date deposited: 09/01/2025
ISSN (print): 0270-9139
ISSN (electronic): 1527-3350
Publisher: Lippincott Williams and Wilkins
URL: https://doi.org/10.1097/HEP.0000000000001174
DOI: 10.1097/HEP.0000000000001174
Data Access Statement: Individual, de-identified participant data used in these analyses are being shared with the US Food and Drug Administration as part of the supplemental New Drug Application. Data are available for analysis on request from any qualified investigator after the approval of a protocol and are subject to the data-sharing requirements of Komodo Health, including a signed data access agreement with the HEROES Study Steering Committee and Komodo Health.
PubMed id: 39630028
Altmetrics provided by Altmetric
