Sotatercept Reduced Morbidity in CTD-PAH Analysis: Rogerio Souza, MD, PhD

Patients with connective tissue disease-associated pulmonary arterial hypertension (CTD-PAH) often face more complex disease burdens and poorer outcomes compared with other pulmonary arterial hypertension (PAH) populations.

“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,” new pooled data presented at the American Thoracic Society 2026 International Conference in Orlando, Florida, suggests that sotatercept may help reduce morbidity and mortality risks in this difficult-to-treat population.¹

The pooled analysis combined findings from the phase 3 STELLAR (NCT04576988), ZENITH (NCT04896008), and HYPERION (NCT04811092) trials, evaluating sotatercept in patients with CTD-PAH. Participants included those with scleroderma, systemic lupus erythematosus, Sjögren’s syndrome, and rheumatoid arthritis, many of whom were already receiving double- or triple-background therapy.

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 São Paulo Medical School, emphasized the complexity of treating CTD-PAH.

“There are a lot of aspects in connective tissue disease-associated PAH, particularly the scleroderma spectrum of the disease, that make it challenging to deal with because they don't only have the vascular disease by itself, but it's usual to have concomitant comorbidities within the same patient,” he said.

The analysis showed that sotatercept reduced the risk of a first major morbidity or mortality event compared with placebo, despite many patients already receiving extensive treatment. According to Souza, that finding is particularly meaningful because the study used strict end points, including death, lung transplantation, and hospitalization lasting at least 24 hours.

“By having those patients under treatment and still being able to decrease morbidity and mortality, it definitely is a step up,” he said. “It's a step ahead in the management of this challenging situation.”

Souza also highlighted sotatercept’s emerging role as a “fourth pathway” therapy in PAH, offering anti-proliferative effects beyond traditional vasodilator-based treatments.

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. Poster 8260.