Division of Cardiovascular Medicine, Department of Internal Medicine, University of Michigan Health System, Ann Arbor, MI, USA.
Merck & Co., Inc., Rahway, NJ, USA.
Adv Ther. 2024 Jan;41(1):130-151. doi: 10.1007/s12325-023-02684-x. Epub 2023 Oct 18.
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. BGT was comprised of mono-, double-, or triple-PAH targeted therapy. Building on STELLAR findings, we employed a population health model to assess the potential long-term clinical impact of sotatercept.
Based on the well-established ESC/ERS 4-strata risk assessment approach, we developed a six-state Markov-type model (low risk, intermediate-low risk, intermediate-high risk, high risk, lung/heart-lung transplant, and death) to compare the clinical outcomes of sotatercept plus BGT versus BGT alone over a lifetime horizon. State-transition probabilities were obtained from STELLAR. Risk stratum-adjusted mortality and lung/heart-lung transplant probabilities were based on COMPERA PAH registry data, and the post-transplant mortality probability was obtained from existing literature. Model outcomes were discounted at 3% annually. Sensitivity analyses were conducted to examine model robustness.
In the base case, sotatercept plus BGT was associated with longer life expectancy from model baseline (16.5 vs 5.1 years) versus BGT alone, leading to 11.5 years gained per patient. Compared with BGT alone, sotatercept plus BGT was further associated with a gain in infused prostacyclin-free life years per patient, along with 683 PAH hospitalizations and 4 lung/heart-lung transplant avoided per 1000 patients.
According to this model, adding sotatercept to BGT increased life expectancy by roughly threefold among patients with PAH while reducing utilization of infused prostacyclin, PAH hospitalizations, and lung/heart-lung transplants. Real-world data are needed to confirm these findings.
ClinicalTrials.gov identifier, NCT04576988 (STELLAR).
肺动脉高压（PAH）是一种罕见的、进行性疾病，与显著的发病率和死亡率相关。3 期 STELLAR 试验测试了 sotatercept 联合背景治疗（BGT）与安慰剂联合 BGT 的疗效。BGT 由单、双或三靶向 PAH 治疗药物组成。基于 STELLAR 的研究结果，我们采用人群健康模型评估 sotatercept 的潜在长期临床影响。
我们根据既定的 ESC/ERS 4 层风险评估方法，开发了一个六状态马尔可夫模型（低风险、中低风险、中高风险、高风险、肺/心肺移植和死亡），以比较 sotatercept 联合 BGT 与单独 BGT 在终生范围内的临床结局。状态转移概率来自 STELLAR 试验。风险分层调整后的死亡率和肺/心肺移植概率基于 COMPERA PAH 登记数据，移植后死亡率概率来自现有文献。模型结果以每年 3%的贴现率进行贴现。进行了敏感性分析以检查模型的稳健性。
在基础情况下，与单独使用 BGT 相比，sotatercept 联合 BGT 可使模型基线的预期寿命延长（16.5 年比 5.1 年），每位患者可延长 11.5 年。与单独使用 BGT 相比，sotatercept 联合 BGT 还可增加每位患者无输注前列环素的生存年数，以及减少 683 例 PAH 住院和 4 例肺/心肺移植。
根据该模型，在 PAH 患者中，与单独使用 BGT 相比，添加 sotatercept 可将预期寿命延长约三倍，同时减少输注前列环素、PAH 住院和肺/心肺移植的使用。需要真实世界的数据来证实这些发现。
ClinicalTrials.gov 标识符，NCT04576988（STELLAR）。
