Efficacy and Safety of Sotatercept in Pulmonary Arterial Hypertension: A Meta-Analysis of RCTs

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