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 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.
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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