近日，德国汉诺威医学院Marius M. Hoeper及其研究小组提出了索特塞普在肺动脉高压高危死亡患者中的作用。相关论文于2025年3月31日发表在《新英格兰医学杂志》上。

背景：sotaterept可改善世界卫生组织（WHO）功能性II级或III级肺动脉高压患者的运动能力并延缓其临床恶化时间。加用索特塞普对晚期肺动脉高压和高死亡风险患者的影响尚不清楚。

方法：在这项3期试验中，课题组人员随机分配了肺动脉高压（WHO功能分类III或IV）和1年死亡风险高的患者（早期和长期肺动脉高压疾病管理注册表2风险评分，≥9）随机分配为每3周接受一次附加索特西普（起始剂量，每公斤体重0.3 mg；升级至目标剂量，每千克0.7 mg）或安慰剂，他们接受了最大耐受剂量。主要终点是在首次事件分析中评估的任何原因导致的死亡、肺移植或因肺动脉高压恶化而住院（≥24小时）的复合终点。

结果：共纳入172例患者（索替西普组和安慰剂组各86例）。基于疗效，试验被提前终止了结果：预先指定的中期分析。索特西普组中有15例患者（17.4%）和安慰剂组中有47例患者（54.7%）发生了至少一个主要终点事件(风险比，0.24；95%置信区间为0.13 ~ 0.43；P＜0.001)。索特西普组有7名患者（8.1%）死于任何原因，安慰剂组有13名患者（15.1%）死于任何原因；肺移植分别为1例（1.2%）和6例（7.0%）；因肺动脉高压加重住院8例（9.3%），43例（50.0%）。索特塞普最常见的不良事件是鼻出血和毛细血管扩张。

研究结果表明，在接受最大耐受剂量的肺动脉高压高危成人中。

附：英文原文

Title: Sotatercept in Patients with Pulmonary Arterial Hypertension at High Risk for Death

Author: Marc Humbert, Vallerie V. McLaughlin, David B. Badesch, H. Ardeschir Ghofrani, J. Simon R. Gibbs, Mardi Gomberg-Maitland, Ioana R. Preston, Rogerio Souza, Aaron B. Waxman, Victor M. Moles, Laurent Savale, Carmine Dario Vizza, Stephan Rosenkranz, Yaru Shi, Barry Miller, Harald S. Mackenzie, Samuel S. Kim, Maria José Loureiro, Mahesh J. Patel, Joerg Koglin, Alexandra G. Cornell, Marius M. Hoeper

Issue&Volume: 2025-03-31

Abstract: BACKGROUND

Sotatercept improves exercise capacity and delays the time to clinical worsening in patients with World Health Organization (WHO) functional class II or III pulmonary arterial hypertension. The effects of add-on sotatercept in patients with advanced pulmonary arterial hypertension and a high risk of death are unclear.

METHODS

In this phase 3 trial, we randomly assigned patients with pulmonary arterial hypertension (WHO functional class III or IV) and a high 1-year risk of death (Registry to Evaluate Early and Long-Term Pulmonary Arterial Hypertension Disease Management Lite 2 risk score, ≥9) who were receiving the maximum tolerated dose of background therapy to receive add-on sotatercept (starting dose, 0.3 mg per kilogram of body weight; escalated to target dose, 0.7 mg per kilogram) or placebo every 3 weeks. The primary end point was a composite of death from any cause, lung transplantation, or hospitalization (≥24 hours) for worsening pulmonary arterial hypertension, assessed in a time-to-first-event analysis.

RESULTS

A total of 172 patients were included (86 each in the sotatercept and placebo groups). The trial was stopped early on the basis of the efficacy results of a prespecified interim analysis. At least one primary end-point event occurred in 15 patients (17.4%) in the sotatercept group and in 47 patients (54.7%) in the placebo group (hazard ratio, 0.24; 95% confidence interval, 0.13 to 0.43; P<0.001). Death from any cause occurred in 7 patients (8.1%) in the sotatercept group and in 13 patients (15.1%) in the placebo group; lung transplantation in 1 patient (1.2%) and 6 patients (7.0%), respectively; and hospitalization for worsening pulmonary arterial hypertension in 8 patients (9.3%) and 43 patients (50.0%). The most common adverse events with sotatercept were epistaxis and telangiectasia.

CONCLUSIONS

Among high-risk adults with pulmonary arterial hypertension who were receiving the maximum tolerated dose of background therapy, treatment with sotatercept resulted in a lower risk of a composite of death from any cause, lung transplantation, or hospitalization (≥24 hours) for worsening pulmonary arterial hypertension than placebo.

DOI: NJ202503310000014

Source: https://www.nejm.org/doi/full/10.1056/NEJMoa2415160