原发性胆汁性胆管炎中使用奥贝胆酸的肝脏真实世界结局（HEROES）：一项试验模拟研究设计
Hepatic real-world outcomes with obeticholic acid in primary biliary cholangitis (HEROES): A trial emulation study design.
作者信息
Brookhart M Alan, Mayne Tracy J, Coombs Charles, Breskin Alexander, Ness Erik, Bessonova Leona, Chu Yucheng Julia, Li Jing, Fried Michael W, Hansen Bettina E, Kowdley Kris V, Jones David, Mells George, Trivedi Palak J, Hiu Shaun, Kareithi Dorcas N, Wason James, Smith Rachel, Seeger John D, Hirschfield Gideon M
机构信息
Department of Population Health Sciences, Duke University, Durham, North Carolina, USA.
Target RWE, Durham, North Carolina, USA.
出版信息
Hepatology. 2025 Jun 1;81(6):1647-1659. doi: 10.1097/HEP.0000000000001174. Epub 2025 Jan 3.
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.
背景与目的
原发性胆汁性胆管炎是一种罕见的进行性肝病。基于碱性磷酸酶降低这一替代终点指标，奥贝胆酸（OCA）已加速获批用于治疗熊去氧胆酸治疗失败的原发性胆汁性胆管炎患者。对两个外部对照组进行的长期安全性扩展分析表明，接受OCA治疗的患者无事件生存期显著延长。这项完全基于真实世界证据的研究评估了OCA治疗对临床结局的影响。
方法与结果
本试验模拟研究使用了来自Komodo Healthcare Map索赔数据库的数据，该数据库与美国国家实验室、移植和死亡数据库相关联。将开始接受OCA治疗的代偿期原发性胆汁性胆管炎患者以及对熊去氧胆酸不耐受/反应不佳的患者与符合OCA治疗条件但未接受OCA治疗的患者进行比较。主要终点为首次发生死亡、肝移植或因肝失代偿住院的时间，采用倾向评分加权Cox比例风险模型进行分析。使用标准化发病比加权使基线预后因素达到平衡。在主要分析中，4174例患者提供了11246个对照索引日期，403例患者提供了OCA索引日期。加权组平衡良好。OCA组和非OCA组的中位（95%CI）随访时间分别为9.3（8.4 - 10.6）个月和17.5（16.2 - 18.6）个月（加权总体；随访至停药）。OCA组发生8起事件，加权对照组发生32起事件（风险比 = 0.37；95%CI = 0.14 - 0.75；p < 0.001）。复合终点各组成部分的效应一致。
结论
我们发现，与未接受OCA治疗的个体相比，接受OCA治疗的个体因肝失代偿、肝移植或死亡而住院的风险降低了63%。
试验注册
HEROES；ClinicalTrials.gov NCT05292872。
Zotero 插件