Opportunities and challenges of pharmacotherapy for pulmonary arterial hypertension in children

Abstract

Pediatric pulmonary hypertension (PAH) is a rare disease that carries a poor prognosis if left untreated. Although there are published guidelines for the treatment of children with pulmonary hypertension, due to the limited number of robust pediatric clinical trials, recommendations are often based on limited data or clinical experience. Furthermore, many practical aspects of care, particularly for the pediatric patient, are learned through experience and best navigated with a multidisciplinary team. While newer PAH therapies have been approved for adults, there is still limited but expanding experience in pediatrics. This new information will help improve the targets of goal‐oriented therapy. Lastly, this review highlights practical aspects in the use of the different therapies available for the treatment of pediatric pulmonary hypertension.

Off‐label use of PAH‐targeted medications approved for adults and their financial coverage by health insurances are vital for children with pulmonary hypertension

“…24,45,46 For that reason, randomized controlled studies with sufficiently high patient numbers and statistical power cannot be expected in the near future, 24,45,46 and however, pharma-sponsored prospective paediatric PH studies are ongoing. 47 For the prostacyclin receptor (IP -) agonist selexipag, the GRIPHON trial did not demonstrate a significant benefit in survival in adults with PAH already on concomitant PAHmedication. 48 However, there was significant improvement of the primary combined clinical endpoint 'mortality or PAHassociated event' (i.e., hospitalization, start of parenteral prostacyclin or oxygen therapy, balloon atrioseptostomy).…”

“…In addition to pharmacotherapy, 24,29,34,47 a catheter interventional or surgical procedure, such as the establishment of a reverse Potts shunt 55,56 or an atrial septostomy, may also be considered for selected PAH patients, 29 although they carry a considerable risk of procedure-related death or morbidity. In addition, off-label subcutaneous implantation of an intravenous treprostinil pump for continuous drug delivery has been reported in very few adolescents (Lenus Pro: 20mL, 40mL).…”

“…One of the main reasons for the lack of prospective/randomized controlled studies in paediatric PAH is that pulmonary hypertensive vascular disease, although underestimated, is a rare disease, particularly in children 24,45,46 . For that reason, randomized controlled studies with sufficiently high patient numbers and statistical power cannot be expected in the near future, 24,45,46 and however, pharma‐sponsored prospective paediatric PH studies are ongoing 47 …”

The many challenges to the field of pediatric pulmonology posed by pediatric pulmonary hypertension and the path forward

“…As reviewed in this supplement, growing awareness of the roles of PH in neonatal lung diseases and their sequelae, especially in association with bronchopulmonary dysplasia, congenital diaphragmatic hernia, persistent pulmonary hypertension of the newborn, Down syndrome, and lethal developmental lung diseases, has led to greater appreciation of the unique nature of pediatric PH 1,4–8 . Pharmacotherapy trials have almost exclusively been performed in patients with Class I PAH and almost entirely in adults, and the need for multicenter randomized clinical trials in children with these diverse forms of PH is further highlighted in this supplement 9 …”

EDITORIAL: The Many Challenges to the Field of Pediatric Pulmonology Posed by Pediatric Pulmonary Hypertension and the Path Forward

“…1,4-8 Pharmacotherapy trials have almost exclusively been performed in patients with Class I PAH and almost entirely in adults, and the need for multicenter randomized clinical trials in children with these diverse forms of PH is further highlighted in this supplement. 9 Based on the recognition of the differences in pediatric diseases and common co-morbidities that complicate PH outcomes, the pediatric committee of the international Pulmonary Vascular Research Institute (PVRI) proposed a more specific classification system for pediatric PVD during the meeting in Panama in 2011 (Table 2). 10 This classification was derived independently from the WSPH Classification system to better reflect different etiologic categories of PH focused on infants, children and adolescents.…”