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

ABSTRACT

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 cm ² ; 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.