A63-08 The Use of Sotatercept in Severe Sarcoidosis-associated Pulmonary Hypertension With Right Ventricular Dysfunction

Precapillary pulmonary hypertension (PH) is prevalent in patients with pulmonary sarcoidosis (PS). When sarcoidosis-associated pulmonary hypertension (SAPH) is present, the 5-year survival in PS decreases from 95% to 59%. Evidence for the use of vasodilator therapies in SAPH is limited but has been associated with improved hemodynamics and functional status. Granulomatous inflammation has been hypothesized as a potential driver of the proliferative pulmonary arteriopathy in SAPH and could potentially explain some of the efficacy of traditional PAH therapies in SAPH. Sotatercept, a novel, first-in-class activin signaling inhibitor that directly targets pulmonary arterial proliferation and arteriopathy has demonstrated improvements in functional status, right ventricular (RV) function, and improved mortality in WHO group 1 PAH. We describe two patients with severe SAPH with RV dysfunction successfully treated with sotatercept. Case 1. A 71-year-old male with PAH and SAPH, Scadding stage IV PS, and chronic iron deficiency on monotherapy with methotrexate presented with worsening dyspnea on exertion (DOE) and hemodynamics consistent with severe RV dysfunction. He was started on oral vasodilator therapy including an endothelin receptor antagonist (ERA), soluble guanylate cyclase (sGC) inhibitor and prostacyclin receptor agonist (PRA), deemed not a candidate for parenteral prostacyclin. His echocardiography and hemodynamics are shown in Table 1. Sotatercept was started in addition to triple therapy, and one year later he was noted to have improved hemodynamics, with decreased RVSP and improved RV function. The patient noted improvement in DOE as well as an improvement in 6MWD and SpO2 nadir during ambulation. Case 2. A 42-year-old female with SAPH, Scadding stage IV PS, with concomitant hepatic, and cutaneous sarcoidosis. RHC at diagnosis showed mPAP 42 mmHg, PCWP 4 mmHg, and PVR 9.4 WU. Sarcoidosis was managed with adalimumab and methotrexate, and she received triple therapy for PH. She developed disease progression with echo evidence of severe RV dysfunction (Table 1) despite maximal medical therapy for her PAH. She was reluctant to start therapy with parenteral prostacyclins. She demonstrated significant improvements after initiation of sotatercept and has tolerated it well. Sotatercept, though approved only for WHO Group 1 PAH, shows promise in SAPH. These cases demonstrate improvement in functional capacity and RV function with good tolerability. Clinical trials for pulmonary hypertension commonly exclude patients with sarcoidosis and treatment is largely anecdotal, but focused studies in SAPH are needed to determine the true efficacy and safety of sotatercept in the management of SAPH. This abstract is funded by: None