Idiopathic pulmonary arterial hypertension (PAH) in infants is a rare, life-threatening condition characterized by elevated pulmonary artery pressure resulting from endothelial dysfunction, vasoconstriction, and vascular remodeling. The treatment options are limited, and the prognosis is poor. In children, 5-year survival following diagnosis remains suboptimal, with estimates of approximately 74% despite advances in therapy. Unfortunately, many patients continue to experience clinical decline despite optimized medical regimens, highlighting the need for novel therapeutic approaches. Sotatercept, an activin receptor type IIB fusion protein, is a new therapeutic agent that modulates the signaling pathway of the transforming growth factor-beta superfamily. It enhances bone morphogenetic protein receptor type 2 signaling, thereby improving pulmonary vascular remodeling and promoting vasodilation. In adult clinical trials, sotatercept has demonstrated improvements in pulmonary vascular resistance, functional capacity, and biomarkers such as brain natriuretic peptide, while reducing the risk of clinical worsening or death, and it was recently approved by the FDA for use in adults to improve exercise capacity and the World Health Organization (WHO) functional class. Despite promising results in adults, data on the use of sotatercept in pediatric patients remain extremely limited and nonexistent for children 1 year of age. Herein, we report the first known use of sotatercept in an infant with severe, treatment-refractory PAH. Treatment was associated with clinical and echocardiographic improvement through 1 year of follow-up, supporting the potential role of sotatercept as an adjunctive therapy in pediatric PAH.
Rathakrishnan et al. (Wed,) studied this question.