First Report of Real World Utilization of an Activin Signaling Inhibitor in Patients With Severe Pulmonary Arterial Hypertension in the Middle East PH RISE-ME Study

Pulmonary arterial hypertension (PAH) remains associated with substantial morbidity and mortality despite advances in combination therapy. Sotatercept, an activin-signaling inhibitor, is a novel disease-modifying therapy targeting pulmonary vascular remodeling. Real-world data from Middle Eastern populations remain limited. We conducted a retrospective single-center cohort study evaluating the real-world effectiveness and safety of Sotatercept in adults with PAH treated at a tertiary pulmonary hypertension expert center in Abu Dhabi, United Arab Emirates, between January 2025 and September 2026. Clinical, echocardiographic, biochemical, and risk-stratification data were extracted from electronic medical records. Primary outcomes were changes in right atrial (RA) area and NT-proBNP. Secondary outcomes included systolic pulmonary arterial pressure (SPAP), TAPSE/SPAP ratio, 6-min walk distance (6MWD), risk profile, and safety. Thirty-six patients were prescribed Sotatercept, of whom 33 received at least one dose. Most patients were female (80.6%), with a mean age of 55 years. Significant reductions occurred in RA area (- 2.67 cm2; 95% CI, -4.16 to -1.18; p < 0.001), NT-proBNP (- 46.7 pmol/L; 95% CI, -87.19 to -20.39; p < 0.001), and SPAP (- 6.00 mmHg; 95% CI, -12.00 to -0.50; p = 0.031). TAPSE increased significantly (+ 0.25 cm; 95% CI, 0.17 to 0.33; p < 0.001), and TAPSE/SPAP improved significantly (+ 0.064; 95% CI, 0.030 to 0.108; p < 0.001). Patients improved by at least one risk category. The 6MWD did not change significantly. Treatment was well tolerated, with no adverse events leading to treatment discontinuation or death; two all-cause deaths occurred during follow-up. In this real-world Middle Eastern PAH cohort, Sotatercept was associated with improved right-heart remodeling, NT-proBNP, and risk profile, with acceptable short-term safety. These findings complement trial evidence and provide early regional support for activin pathway inhibition in routine practice.