Hepatic real-world outcomes with obeticholic acid in primary biliary cholangitis (HEROES): A trial emulation study design.

IF 12.9 1区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY
M Alan Brookhart, Tracy J Mayne, Charles Coombs, Alexander Breskin, Erik Ness, Leona Bessonova, Yucheng Julia Chu, Jing Li, Michael W Fried, Bettina E Hansen, Kris V Kowdley, David Jones, George Mells, Palak J Trivedi, Shaun Hiu, Dorcas N Kareithi, James Wason, Rachel Smith, John D Seeger, Gideon M Hirschfield
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引用次数: 0

Abstract

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.

Trial registration: HEROES; ClinicalTrials.gov NCT05292872.

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来源期刊
Hepatology
Hepatology 医学-胃肠肝病学
CiteScore
27.50
自引率
3.70%
发文量
609
审稿时长
1 months
期刊介绍: HEPATOLOGY is recognized as the leading publication in the field of liver disease. It features original, peer-reviewed articles covering various aspects of liver structure, function, and disease. The journal's distinguished Editorial Board carefully selects the best articles each month, focusing on topics including immunology, chronic hepatitis, viral hepatitis, cirrhosis, genetic and metabolic liver diseases, liver cancer, and drug metabolism.
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