D1.539 - Efficacy and safety of sotatercept in pulmonary arterial hypertension: a systematic review and meta‐analysis of randomized controlled trials

PAH is a progressive disease that causes pulmonary vascular remodeling and significant mortality rates. Sotatercept, a new activin signaling inhibitor, has the potential to treat underlying vascular dysfunction beyond traditional vasodilator therapy. This meta-analysis aims to assess the overall efficacy of Sotatercept in treating PAH.

We searched PubMed, Embase, and the Cochrane Library from inception until Dec 15, 2025, for randomized controlled trials sotatercept to placebo in adults with PAH were included. The primary efficacy endpoint was clinical worsening defined as composite of death from any cause, lung transplantation, or hospitalization (≥24 hours) for worsening pulmonary arterial hypertension. The secondry endpoint were death, improved WHO functional and serious adverse event. Data was pooled as risk ratio (RR) with a 95% confidence interval (CI) using the restricted maximum likelihood (REML) random effects.

: Four RCTs were included (N= 921 patients). Based on pooled analysis, compared with placebo, Sotatercept significantly lower incidence of composite of death from any cause, lung transplantation, or hospitalization (≥24 hours) for worsening pulmonary arterial (RR: 0.28, 95% CI: 0.21 to 0.38, p < 0001; I²=0%), ketamine significantly improved WHO functional (RR: 1.74, 95% CI: 1.35 to 2.24, p < 001; I²=15.1%), ketamine devcres rate of serious adverse event  (RR: 0.82, 95% CI: 0.68 to 0.99, p = 0.04; I²=0%) and without decrease rate of death  (RR: 0.63, 95% CI: 0.33 to 1.21, p = 0.16; I²=18.1%) 

Sotatercept significantly decrease composite of death from any cause, lung transplantation, or hospitalization (≥24 hours) for worsening pulmonary arterial hypertension,

and serious adverse events in patients with PAH while improved WHO functional. However, the effect on all cause of death was not statistically significant.  More trials with long follow up are needed to assess the clinical relevance of these findings.