Abstract Introduction Patients with pulmonary arterial hypertension (PAH) require double or triple maximally tolerated combination therapy, yet progression persists in many cases. Sotatercept, a first-in-class activin signaling inhibitor, reverses pulmonary vascular remodeling and improves hemodynamic parameters. We report a case of connective tissue disease-associated PAH (CTD-PAH) where the addition of sotatercept allowed for the safe reduction of high-dose intravenous prostacyclin therapy while achieving clinical and hemodynamic improvement. Case Presentation A 54-year-old female with history of CTD-PAH diagnosed in 2009 with pulmonary vascular resistance (PVR) of 15 wood unit (WU), managed with endothelial receptor antagonist (ambrisentan followed by macitentan) in combination with PDE5 inhibitor (sildenafil followed by tadalafil) and subcutaneous treprostinil. These treatments resulted in marked improvement (PVR=6.8 WU). In July 2016, her PAH was adequately controlled, allowing for a switch from treprostinil to oral selexipag (PVR=3.9 WU). By 2023 worsening symptoms lead to re-initiation of intravenous treprostinil (PVR=11.1 WU) gradually escalated to 135 ng/kg/min. Despite therapy, she experienced progressive right heart failure and was deemed ineligible for lung transplant. In early 2024, repeat hemodynamics revealed a rising PVR (8.4 WU) requiring initiation of subcutaneous sotatercept as a fourth agent. She developed severe abdominal pain and uncontrolled diarrhea prompting temporary discontinuation of sotatercept. Excessive treprostinil dosing was identified as a contributing factor, and the treprostinil dose was gradually reduced. By late 2024, clinical and hemodynamics improvement (PVR= 5.7 WU) allowed further down titration of treprostinil while continuing sotatercept 0.7 mg/kg every 3 weeks. Improvement in NT-proBNP from 2800 to 346 pg.dl, DLCO from 68% to 80% predicted, and six-minute walk distances from 250 m to 319 meters were noted. By August 2025, symptoms improved, weight increased by 20 lbs and she was transitioned to oral treprostinil while maintaining sotatercept, opsimut and tadalafil therapies. Discussion The long-term management of PAH remains challenging due to progressive hemodynamic deterioration, right ventricular dysfunction, and eventual failure of standard therapies. This case highlights the evolving therapeutic landscape of PAH and underscores the potential role of novel agents, such as sotatercept, in the management of complex PAH patients. Addition of sotatercept may result in side-effects attributable to excess PAH treatment. As the pulmonary vascular remodeling improves, need for PAH therapy may decrease resulting in downtitration of PAH meds while maintaining clinical improvement. This abstract is funded by: None
Safdar et al. (Fri,) studied this question.