Bleeding Risk Considerations With Sotatercept in CTD-PAH: Rogerio Souza, MD, PhD

Managing connective tissue disease–associated pulmonary arterial hypertension (CTD-PAH) requires clinicians to balance overlapping disease processes, evolving symptoms, and treatment-related risks. At the American Thoracic Society International Conference 2026 in Orlando, Florida, investigators discussed new pooled data from the STELLAR (NCT04576988), ZENITH (NCT04896008), and HYPERION (NCT04811092) trials evaluating sotatercept in this particularly complex patient population.¹

In an interview with The American Journal of Managed Care^®, Rogerio Souza, MD, PhD, professor of pulmonary medicine and head of the Pulmonary Circulation Program at the University of Sao Paulo Medical School, explained that one of the greatest challenges in CTD-PAH is determining what is actually driving clinical deterioration in a patient.

“It’s in CTD to diagnose progression is even more challenging because you have a huge confounding factor, which is the CTD itself,” he said. “So a patient that is deteriorating might be deteriorating because of the pulmonary vascular disease, but also because of disease activity.”

The pooled analysis showed that sotatercept produced hemodynamic responses in CTD-PAH that were similar to responses previously observed in other PAH subgroups, a finding Souza described as reassuring. He noted that this was the first study to demonstrate comparable hemodynamic response patterns between CTD-associated and non-CTD–associated PAH populations.

The discussion also highlighted important safety considerations, particularly surrounding bleeding risk in patients already predisposed to bleeding complications. Souza emphasized that while sotatercept’s overall risk-benefit profile remains favorable, clinicians should closely evaluate concurrent anticoagulation use in patients with CTD-PAH, especially those with scleroderma-spectrum disease.

“The risk-benefit ratio for the use of sotatercept is clearly in favor of the use of sotatercept,” Souza said. “But even though you know that you’re already with a patient who is more prone to having bleeding events, and you’re using a drug that is related to an increased incidence of bleeding events.”

Although more than 70% of participants had scleroderma, Souza noted the treatment responses appeared generally consistent across connective tissue disease subtypes, though subgroup sizes remain too small for definitive comparisons.

References

1. Souza R, Badesch DB, Gibbs S, et al. Efficacy and safety of sotatercept in patients with pulmonary arterial hypertension (PAH) associated with connective tissue disease (CTD): A pooled analysis from STELLAR, ZENITH, and HYPERION. Presented at: American Thoracic Society 2026 International Conference; May 17-20, 2026; Orlando, Florida.