Clinical, hemodynamic, and safety outcomes of sotatercept in pulmonary arterial hypertension: A meta-analysis of randomized trials with time-to-event data

Authors

• Mohamed R Murad, Medical Research Group of Egypt (MRGE), Negida Academy, Arlington, MA, USA.
• Ameer Awashra, Department of Medicine, An-Najah National University, Rafidia Street, P.O. Box 7, Nablus, West Bank P4110257, Palestine.
• Mohamed S Elgendy, Faculty of Medicine, Tanta University, Tanta, Gharbia, Egypt.
• Ahmed Wahdan Kasem, Medical Research Group of Egypt (MRGE), Negida Academy, Arlington, MA, USA.
• Abdalhakim Shubietah, Advocate Health - MidwestFollow
• Fadi Safi, Department of Pulmonary and Critical Care Medicine, University of Toledo, Toledo, OH, USA.

Recommended Citation

R Murad M, Awashra A, S Elgendy M, Kasem AW, Shubietah A, Safi F. Clinical, hemodynamic, and safety outcomes of sotatercept in pulmonary arterial hypertension: a meta-analysis of randomized trials with time-to-event data. Ther Adv Respir Dis. 2026;20:17534666261459209. doi:10.1177/17534666261459209

Affiliations

Advocate Illinois Masonic Medical Center

Abstract

Background: Pulmonary arterial hypertension (PAH) remains progressive despite contemporary background therapy. Sotatercept is a novel activin signaling inhibitor that targets pulmonary vascular remodeling and may improve clinical and hemodynamic outcomes.

Objectives: To evaluate the efficacy, hemodynamic effects, and safety of sotatercept in patients with PAH.

Design: Systematic review and meta-analysis of randomized controlled trials (RCTs).

Data sources and methods: Five electronic databases were searched through October 2, 2025, for eligible RCTs. Time-to-event outcomes were analyzed using pooled individual patient data with hazard ratios (HRs), while secondary outcomes were assessed using random-effects risk ratios (RRs) and mean differences (MDs), with 95% confidence intervals (CI). Trial-sequential analysis (TSA) evaluated the conclusiveness of results.

Results: In four RCTs (n = 889), sotatercept reduced clinical worsening or death by 77% (HR 0.23, 95% CI 0.16-0.32, p < 0.001) and prolonged event-free survival by ~40 weeks. World Health Organization (WHO) functional class improved in 40.3% vs 24.3% (RR 1.71, 95% CI 1.32-2.21), and 6-minute walk distance increased by MD 30.27 m (95% CI 13.45-47.08), while pulmonary vascular resistance (PVR) declined significantly (MD -247 dyn·s·cm-⁵, 95% CI -301.7; -192.2). Serious adverse events were slightly less frequent with sotatercept (26.2% vs 31.7%, RR 0.83); however, total bleeding (37.9% vs 18.7%, RR 2.00), epistaxis (26.7% vs 5.4%, RR 4.89), and telangiectasia (19.8% vs 6.4%, RR 3.24) were more common. TSA revealed conclusiveness in clinical worsening, WHO functional class, and PVR, as well as increases in bleeding events and epistaxis.

Conclusion: Sotatercept significantly improves clinical outcomes and extends event-free survival in PAH, with an acceptable safety profile; however, caution is warranted regarding bleeding events. These results support its role as an add-on therapy in PAH management.

Type

Article

PubMed ID

42312805