Lifesaving Compassionate‐Use of Sotatercept in a 12‐Year‐old With Idiopathic Pulmonary Arterial Hypertension

ABSTRACT

Pediatric idiopathic pulmonary arterial hypertension (IPAH) refractory to maximal medical therapy is associated with high morbidity and mortality, and therapeutic options remain limited. We describe a 12‐year‐old girl with end‐stage IPAH who developed acute decompensated right heart failure despite triple combination therapy, including high‐dose prostacyclin. Escalation to intravenous epoprostenol failed to result in clinical or hemodynamic improvement. Following multidisciplinary discussion, ethical approval, and informed consent, sotatercept was initiated under compassionate use. Sotatercept therapy resulted in rapid and marked clinical recovery, including improvement in World Health Organization functional class (WHO FC) from IV to II, substantial increase in 6‐min walk distance, normalization of NT‐proBNP levels, and significant echocardiographic and invasive hemodynamic improvement. This case highlights the potential role of sotatercept as a rescue therapy in pediatric IPAH refractory to conventional treatment.

1. Case Description

A 12‐year‐old girl with a known diagnosis of idiopathic pulmonary arterial hypertension (IPAH) was admitted with severe acute decompensation of right heart failure. The diagnosis was established 15 months earlier, genetic studies were not performed. Prior to admission, she was receiving triple combination therapy consisting of high‐dose subcutaneous Treprostinil (in a gradually increasing dose up to dose 184 ng/kg/min), bosentan, and a phosphodiesterase‐5 inhibitor (initially sildenafil, later switched to riociguat which was slowly escalated 3 months before deterioration), along with diuretics. Despite therapy, she remained in World Health Organization functional class (WHO FC) III and was listed for lung transplantation. Her outpatient 6 min walk distance (6MWD) ranged from 123 to 276 m, with NT‐proBNP levels between 1595 and 3665 pg/mL. On admission, the patient deteriorated to WHO FC IV, presenting with hypoxemia, generalized edema, massive ascites, and markedly elevated NT‐proBNP (7184 pg/mL). Transthoracic echocardiography revealed severe right ventricular dilation with left ventricular compression, pericardial effusion, peak tricuspid regurgitation velocity of 4,65 m/s, and pulmonary artery acceleration time of 78 ms. An extensive soft‐tissue infection was noted at the subcutaneous treprostinil infusion site (Figure 1A,D). Oxygen therapy was initiated, and a new subcutaneous access site was established. Hemodynamic stabilization with dopamine and levosimendan was achieved; however, no sustained clinical improvement was observed. The patient was transitioned to intravenous epoprostenol, which was gradually escalated to 122 ng/kg/min [1]. Recurrent massive ascites refractory to medical therapy necessitated repeated paracentesis and insertion of a Tenckhoff catheter. Given the lack of response to maximal prostacyclin therapy, sotatercept was initiated as salvage treatment following multidisciplinary discussion, ethics committee approval, and written informed consent from the patient's legal guardians. Sotatercept therapy was initiated at a starting dose of 15 mg (at a body weight of 48 kg and a dose of 0.312 mg/kg) followed by subsequent doses of 30 mg. Over the subsequent weeks, the patient demonstrated marked clinical improvement. WHO FC improved to II, 6MWD increased to 507 m (in 8 weeks after admission), and NT‐proBNP decreased to 159 pg/mL (in 10 weeks after admission). The Tenckhoff catheter was removed. Follow‐up echocardiography showed recovery of right ventricular function (right ventricular fractional area change > 35%), reduction of tricuspid regurgitation velocity to 2,9 m/s, prolongation of pulmonary artery acceleration time to 164 ms, improved left ventricular filling, and reduction of pericardial effusion (Figure 1B,C,E,F). Repeat after 5 months right heart catheterization confirmed significant hemodynamic improvement, with pulmonary vascular resistance index decreasing from 17,24 to 6.05 WU·m², mean pulmonary arterial pressure from 70 to 42 mmHg, mean right atrium pressure from 17 to 11 mmHg, cardiac index increasing from 3.19 to 7.5 l/min/m², and no change in pulmonary capillary wedge pressure. After several months, the sotatercept dose was increased to 45 mg. The patient remains under our care and has continued therapy with for a total of 10 months. Furthermore, background specific therapy has remained unchanged to date. Among the observed sotatercept‐related adverse events, intermittent asymptomatic thrombocytopenia was noted in laboratory tests, along with cutaneous telangiectasias. The patient denies bleeding or headaches, and no erythrocytosis has been observed.

Figure 1.

(A and D)—Infected skin around the subcutaneous injection site with treprostinil infusion. (B)—Echocardiography—apical four‐chamber view before sotatercept therapy; (C)—Echocardiography—apical four‐chamber view after sotatercept therapy, 4 months later; (E)—Echocardiography—short axis view before sotatercept therapy; (F)—Echocardiography—short axis view after sotatercept therapy, 4 months later.

2. Discussion

This case illustrates the challenges of managing end‐stage pediatric IPAH refractory to conventional therapy. Although intravenous epoprostenol remains the gold standard for severe PAH, our patient failed to respond despite aggressive dose escalation. We believe that a massive soft‐tissue infection and edema at the subcutaneous pump insertion site resulted in impaired absorption of treprostinil and reduced therapeutic efficacy prior to admission. Sotatercept has emerged as a novel disease‐modifying therapy targeting pulmonary vascular remodeling via inhibition of activin signaling [2]. While randomized trials have demonstrated significant benefits in adult PAH [3, 4, 5], pediatric experience is limited [6]. In this critically ill patient, sotatercept was associated with dramatic clinical, functional, and hemodynamic improvement, potentially averting the need for urgent lung transplantation. Compassionate use of sotatercept may be considered as a rescue option in selected pediatric patients with severe IPAH refractory to maximal medical therapy, following careful ethical review and informed consent. Further prospective studies are needed to establish its safety and efficacy in the pediatric population.

Author Contribution

Weronika Pelczar‐Płachta: conceptualization, clinical data acquisition, and drafting of the original manuscript. Rafał Surmacz: critical revision of the manuscript and intellectual contributions to the case analysis. Waldemar Bobkowski: literature review support, critical revision of the manuscript, and final clinical supervision. All authors contributed to the final editing, reviewed the results, and approved the submitted version of the manuscript.

Funding

The authors have nothing to report.

Ethics Statement

Committee on Bioethics, Poznan University of Medical Sciences, Poznań, Poland (N373/25).

Conflicts of Interest

The authors declare no conflicts of interest.

Guarantor

Weronika Pelczar‐Płachta is the guarantor of this article.