Off-Label Sotatercept Use in Pediatric Pulmonary Arterial Hypertension: A Single-Center Retrospective Hemodynamic Study

Background Sotatercept, a first-in-class activin signaling inhibitor, has demonstrated disease-modifying efficacy in adults with pulmonary arterial hypertension (PAH). Pediatric data remain limited to ongoing clinical trials. Methods We conducted an IRB-approved, single-center retrospective analysis of pediatric patients with WHO Group 1 or Group 3 PAH treated with off-label sotatercept at Rady Children’s Hospital / UC San Diego. All patients had received maximal background triple therapy yet demonstrated persistent symptoms or adverse hemodynamics. Right heart catheterization was performed before sotatercept initiation and at approximately 24 weeks thereafter. Hemodynamic parameters were analyzed descriptively. Results Seven pediatric patients (median age 14 years; range 4–19) were included. Diagnoses comprised idiopathic PAH, heritable PAH, and PAH associated with congenital heart disease or congenital diaphragmatic hernia. Following sotatercept initiation, the majority of patients demonstrated reductions in pulmonary vascular resistance index (PVRI) and mean pulmonary artery pressure (mPAP), with heterogeneity in magnitude of response. Pulmonary capillary wedge pressure (PCWP) remained stable in all patients. Conclusions In this small, highly selected pediatric cohort with advanced PAH refractory to triple therapy, off-label sotatercept was associated with favorable hemodynamic trends at 24 weeks. These findings support biologic plausibility suggested by adult randomized trials and underscore the urgent need for prospective pediatric studies.