Sotatercept as a Treatment for Pulmonary Hypertension Associated With Connective Tissue Disease and ILD

Sotatercept is a drug approved for pulmonary arterial hypertension (PAH) that improves mortality, right ventricular function, functional class, NT-proBNP, and 6-minute walk distance. However, no clinical trials support its use in patients with pulmonary hypertension (PH) and interstitial lung disease (ILD), and respiratory adverse effects have been reported due to the development of intrapulmonary shunts. We report a 65-year-old woman with stable fibrotic ILD associated with Sjögren-antisynthetase overlap syndrome who developed severe precapillary PH. Despite treatment with inhaled treprostinil and tadalafil, she showed no clinical or hemodynamic improvement. Sotatercept and macitentan were initiated to improve hemodynamics and serve as a bridge to transplantation. After three months, the patient achieved functional class I, BNP reduction, normalization of echocardiographic PH findings, and marked hemodynamic improvement. Despite concerns regarding sotatercept-associated intrapulmonary shunts and hypoxemia, basal oxygen saturation improved from 93% to 96%. Bilateral lung transplantation was performed without immediate complications. This case supports further evaluation of the efficacy and safety profile of sotatercept in PH with concomitant ILD.