Durability of sotatercept response in pulmonary hypertension: Insights from extended real-world follow-up

BACKGROUND: Sotatercept, an activin receptor ligand trap, has demonstrated significant short-term hemodynamic improvements in pulmonary hypertension (PH) based on clinical trials. However, evidence regarding long-term outcomes in real-world settings remains limited. METHODS: Using data from the TriNetX global federated health research network covering 102 healthcare organizations, we conducted a retrospective cohort study comparing 454 patients with primary PH receiving sotatercept to 963,386 primary PH patients not receiving sotatercept. After 1:1 propensity score matching to balance baseline characteristics, we assessed outcomes and cox proportional hazards was used. Primary outcome included all-cause mortality and seondary outcome included lung transplantation and adverse events. RESULTS: From 156 healthcare organizations in the TriNetX Global Collaborative Network, 963,386 patients with PAH not receiving sotatercept and 454 receiving sotatercept met inclusion criteria. After 1:1 propensity matching, 346 patients per cohort were well-balanced (standardized differences <0.2). During follow-up (179 ± 103 vs 246 ± 100 days), all-cause mortality was significantly lower with sotatercept (3.2 % vs 30.4 %; absolute risk reduction 27.2 %, 95 % CI 22.0-32.4; p < 0.001). Kaplan-Meier analysis confirmed superior survival (95.5 % vs 45.2 %; log-rank p = 0.010). The composite safety endpoint occurred less frequently in the sotatercept group (10.2 % vs 26.9 %; p < 0.001). CONCLUSIONS: In this large real-world analysis from the TriNetX Global Collaborative Network, sotatercept use in patients with pulmonary arterial hypertension was associated with markedly lower all-cause mortality, absence of lung transplantation events, and fewer adverse outcomes compared with matched controls.