Efficacy and safety of sotatercept in pulmonary arterial hypertension: a meta-analysis of randomized controlled trials.

Introduction: To evaluate the efficacy and safety of sotatercept, an activin signaling inhibitor, in pulmonary arterial hypertension (PAH).

Methods: We searched PubMed, Embase, and the Cochrane Library for randomized controlled trials (RCTs) comparing sotatercept versus placebo in PAH. We calculated pooled risk ratios (RR) and mean differences (MD) with their 95% confidence intervals (CI) using a random-effects model. Heterogeneity was assessed with I² statistics. The GRADE approach was used to assess the certainty of evidence.

Results: Three RCTs comprising 601 patients were included. Compared to placebo, sotatercept significantly improved 6-minute walk distance (MD 40.57 m; 95% CI 26.64 to 54.5; p < 0.01), and WHO functional class (RR 2.04; 95% CI 1.53 to 2.7; p < 0.01). Sotatercept reduced pulmonary vascular resistance (MD -233.18 dyn·sec·cm^-5; 95% CI -295.84 to -170.52; p < 0.01) and pulmonary artery pressure (MD -14.94 mmHg; 95% CI -19.62 to -10.27; p < 0.01) at study end. No significant differences were observed in all-cause mortality or NT-proBNP levels. Sotatercept was associated with epistaxis, increased hemoglobin, and telangiectasia adverse events.

Conclusions: Sotatercept improves exercise capacity, WHO functional class and pulmonary hemodynamics in PAH, with an acceptable safety profile. Long-term studies are needed to confirm sustained benefits.

Protocol registration: www.crd.york.ac.uk/prospero identifier is CRD420251032174.