Alsumali Adnan, McLaughlin Vallerie, Chevure Jestinah, Klok Rogier, Zhang Wenjie, Martinez Eliana C, Pausch Christine, De Oliveira Pena Janethe, van de Wetering Gijs, Jootun Murvin, Lautsch Dominik, Hoeper Marius M
BARDS-Health Economics and Decision Science, Merck & Co., Inc., 126 E. Lincoln Ave., Rahway, NJ, 07065, USA.
Division of Cardiovascular Medicine, Department of Internal Medicine, University of Michigan Health System, Ann Arbor, MI, USA.
Adv Ther. 2025 Jun 17. doi: 10.1007/s12325-025-03241-4.
Pulmonary arterial hypertension (PAH) is a rare, progressive disease associated with significant morbidity and mortality. The phase 3 STELLAR trial tested sotatercept plus background therapy (BGT) versus placebo plus BGT, where BGT included mono-, double-, or triple-PAH targeted therapy. Building on the trial's findings, a population health model was recently published assessing the long-term clinical impact of sotatercept. This analysis expands on this model and compares the clinical outcomes of immediate treatment initiation with sotatercept plus BGT against delayed treatment initiation with sotatercept plus BGT using a six-state Markov-type model and over a lifetime horizon.
State-transition probabilities were obtained from STELLAR, while mortality rates adjusted for risk strata and probabilities of lung/heart-lung transplants were derived from COMPERA PAH registry data and literature.
In the base case, a 2-year delay in treatment with sotatercept plus BGT resulted in an average of 12.4 years life expectancy, whereas immediate initiation of sotatercept led to an average of 16.5 years, a difference of 4.1 years. Immediate treatment with sotatercept plus BGT was also associated with a gain in infused prostacyclin-free life-years and resulted in 210 PAH hospitalizations avoided and 5 lung/heart-lung transplant avoided per 1000 patients.
This research suggests that early addition of sotatercept to BGT has the potential to increase life expectancy among patients with PAH and to reduce PAH hospitalizations, prostacyclin-use, and lung/heart-lung transplants needs. Real-world data are needed to confirm these findings, guiding clinicians and healthcare decision-makers in optimizing PAH treatment strategies.
ClinicalTrials.gov identifier, NCT04576988 (STELLAR).
肺动脉高压（PAH）是一种罕见的进行性疾病，具有较高的发病率和死亡率。3期STELLAR试验比较了索他西普联合背景治疗（BGT）与安慰剂联合BGT的疗效，其中BGT包括单药、双药或三药PAH靶向治疗。基于该试验结果，最近发表了一项人群健康模型，评估了索他西普的长期临床影响。本分析在此模型基础上进行扩展，使用六状态马尔可夫型模型，在终身范围内比较索他西普联合BGT立即开始治疗与延迟开始治疗的临床结局。
状态转移概率来自STELLAR试验，而根据风险分层调整的死亡率以及肺/心肺移植概率则来自COMPERA PAH注册数据和文献。
在基础病例中，索他西普联合BGT治疗延迟2年导致平均预期寿命为12.4年，而立即开始使用索他西普则导致平均预期寿命为16.5年，相差4.1年。索他西普联合BGT立即治疗还与无静脉注射前列环素生存年数增加相关，每1000例患者可避免210次PAH住院和5次肺/心肺移植。
本研究表明，在BGT基础上早期添加索他西普有可能提高PAH患者的预期寿命，并减少PAH住院、前列环素使用以及肺/心肺移植需求。需要真实世界数据来证实这些发现，为临床医生和医疗保健决策者优化PAH治疗策略提供指导。
ClinicalTrials.gov标识符，NCT04576988（STELLAR）。
