马昔腾坦治疗门脉性肺动脉高压的安全性：OPUS/OrPHeUS联合研究的真实世界证据
Safety of Macitentan for the Treatment of Portopulmonary Hypertension: Real-World Evidence from the Combined OPUS/OrPHeUS Studies.
作者信息
Kim Nick H, Chin Kelly M, McLaughlin Vallerie V, DuBrock Hilary, Restrepo-Jaramillo Ricardo, Safdar Zeenat, MacDonald Gwen, Martin Nicolas, Rosenberg Daniel, Solonets Maria, Channick Richard
机构信息
UC San Diego Health, Division of Pulmonary, Critical Care, and Sleep Medicine, University of California San Diego, 9300 Campus Point Dr, La Jolla, CA, 92037-7381, USA.
UT Southwestern Medical Center, Dallas, TX, USA.
出版信息
Pulm Ther. 2024 Mar;10(1):85-107. doi: 10.1007/s41030-023-00251-x. Epub 2024 Jan 7.
INTRODUCTION
Portopulmonary hypertension (PoPH) carries a worse prognosis than other forms of pulmonary arterial hypertension (PAH). Data regarding use of PAH-specific therapies in patients with PoPH are sparse as they are usually excluded from clinical trials. This analysis describes patient characteristics, treatment patterns, outcomes, and safety profiles in patients with PoPH newly initiating macitentan in the USA using the OPUS/OrPHeUS combined dataset.
METHODS
OPUS was a prospective, US, multicenter, observational drug registry (April 2014-June 2020); OrPHeUS was a retrospective, US, multicenter chart review (October 2013-March 2017). Additional information regarding patients' liver disease was retrospectively collected for patients with PoPH in OPUS.
RESULTS
The OPUS/OrPHeUS dataset included 206 patients with PoPH (median age 58 years; 52.4% female), with baseline cirrhosis and liver test abnormalities reported in 72.8% and 31.6% of patients respectively. Macitentan was initiated as combination therapy in 74.8% of patients and median (Q1, Q3) exposure to macitentan was 11.9 (3.1, 26.0) months. One-year Kaplan-Meier estimates (95% confidence limit, CL) of patients free from all-cause hospitalization and survival were 48.6% (40.7, 56.0) and 82.2% (75.1, 87.4). Of the 96 patients with PoPH in OPUS, 29.2% were classified as in need of liver transplant due to underlying liver disease during the study; transplant waitlist registration was precluded because of PAH severity for 32.1% and 17.9% were transplanted. Hepatic adverse events (HAE) were experienced by 49.0% of patients; the most common being increased bilirubin (16.0%), ascites (7.3%), and hepatic encephalopathy (5.8%); 1.5% and 21.8% of patients discontinued macitentan as a result of HAE and non-hepatic adverse events.
CONCLUSION
There were no unexpected safety findings in patients with PoPH treated with macitentan. These data add to the evidence supporting the safety and tolerability of macitentan in patients with PoPH. A graphical abstract is available with this article.
TRIAL REGISTRATION
OPsumit® Users Registry (OPUS): NCT02126943; OPsumit® Historical Users cohort (OrPHeUS): NCT03197688; www.
CLINICALTRIALS
gov .
引言
与其他形式的肺动脉高压（PAH）相比，门脉性肺动脉高压（PoPH）的预后更差。关于PoPH患者使用PAH特异性疗法的数据很少，因为他们通常被排除在临床试验之外。本分析使用OPUS/OrPHeUS联合数据集描述了美国新开始使用马昔腾坦的PoPH患者的特征、治疗模式、结局和安全性概况。
方法
OPUS是一项前瞻性、美国多中心观察性药物登记研究（2014年4月至2020年6月）；OrPHeUS是一项回顾性、美国多中心图表审查研究（2013年10月至2017年3月）。对OPUS中PoPH患者的肝病相关附加信息进行了回顾性收集。
结果
OPUS/OrPHeUS数据集包括206例PoPH患者（中位年龄58岁；52.4%为女性），分别有72.8%和31.6%的患者基线时有肝硬化和肝功能检查异常。74.8%的患者开始将马昔腾坦作为联合治疗，马昔腾坦的中位（Q1，Q3）暴露时间为11.9（3.1，26.0）个月。无全因住院和生存的患者的1年Kaplan-Meier估计值（95%置信区间，CL）分别为48.6%（40.7，56.0）和82.2%（75.1，87.4）。在OPUS的96例PoPH患者中，29.2%在研究期间因潜在肝病被分类为需要肝移植；32.1%因PAH严重程度而未进行移植等待名单登记，17.9%进行了移植。49.0%的患者发生了肝脏不良事件（HAE）；最常见的是胆红素升高（16.0%）、腹水（7.3%）和肝性脑病（5.8%）；1.5%和21.8%的患者因HAE和非肝脏不良事件停用了马昔腾坦。
结论
接受马昔腾坦治疗的PoPH患者未发现意外的安全性结果。这些数据进一步证明了马昔腾坦在PoPH患者中的安全性和耐受性。本文提供了图形摘要。
试验注册
OPsumit®用户登记研究（OPUS）：NCT0212******；OPsumit®历史用户队列（OrPHeUS）：NCT0319******；www.clinicaltrials.gov 。
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