Introduction: Pulmonary arterial hypertension (PAH) is a fatal progressive disease that cause pulmonary vascular remodelling and right heart problems. Current treatment targets vasodilation, but skips the underlying problem of remodelling, which results in poor outcomes despite various treatments. Sotatercept is a breakthrough drug which targets transforming growth factor β imbalance and therefore targets this vascular remodelling, which is a root cause for PAH. We assessed its efficacy and safety in this meta analysis. Methods: A systematic search of PubMed, Embase, Google Scholar and Cochrane databases was conducted to find studies that evaluate efficacy and safety of Sotatercept in patients with PAH. Three randomized controlled trials met inclusion criteria. Data were pooled using inverse variance weighting with a random-effects model in R Studio. Forest plots were used to illustrate pooled effect estimates, and heterogeneity was assessed. Results: Three randomized controlled trials (PULSAR, STELLAR, and ZENITH) with 569 participants were included in our meta-analysis. Compared to placebo, sotatercept significantly improved 6-minute walk distance by 38.12 meters (95% CI: 21.92 to 54.32; P < 0.0001) and reduced pulmonary vascular resistance by 242.90 dyn·sec·cm−5 (95% CI: -287.46 to -198.33; P < 0.0001). NT-proBNP levels showed a reduction of 1037.74 pg/ml (95% CI: -2103.73 to 28.26; P = 0.0564), though this did not reach statistical significance. Safety analysis revealed that although sotatercept looks to have low Adverse events (RR = 0.99; 95% CI: 0.92 to 1.07; P = 0.85), serious adverse events (RR = 0.85; 95% CI: 0.54 to 1.34; P = 0.49) and discontinuation due to drug adverse events (RR = 0.44; 95% CI: 0.10 to 1.99; P = 0.29), they didn’t reached statistical significance. But thrombocytopenia seems to be more common in people who took sotatercept than to placebo (RR = 2.03; 95% CI: 1.02 to 4.03; P = 0.04) and it is statistically significant. Conclusions: Sotatercept demonstrated significant efficacy in PAH by increasing exercise capacity and other pulmonary haemodynamics. Safety profile is also comparable to that of placebo, with slightly higher risk for thrombocytopenia. Future research should focus on optimal dosing strategies and long term outcomes and its efficacy in specific PAH subtype
Krishnamaneni et al. (Sun,) studied this question.