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

Abstract

Pulmonary hypertension (PH) is a progressive disease defined by chronic elevation of pulmonary artery pressure. The underlying causes of PH are diverse and include pathological changes in the pulmonary vessels, the pulmonary parenchyma or interstitium and small or dysfunctional left-sided heart structures. Over the last two decades, echocardiography, the primary diagnostic tool in paediatric PH, has developed into an advanced imaging technology with usually great image quality and prognostic impact. [1][2][3][4][5][6][7][8][9][10] Prior to the modern area of PH therapy, the average life expectancy after diagnosis has been 10 months for children with pulmonary arterial hypertension (PAH). 11 The development and availability of new, so-called "targeted" or "advanced" therapies, which are approved for adults with PAH, have significantly improved quality of life and life expectancy of paediatric PAH patients as well. 12,13 The pathogenesis of pulmonary hypertensive vascular disease, however, in most cases, is still chronically progressive: In end-stage PH, defined as advanced pulmonary vascular disease (PVD) and severe right ventricular (RV) dysfunction, [14][15][16][17][18] bilateral lung transplantation remains the only treatment option. [19][20][21]

Case report: Rescue treatment with add-on selexipag in a preterm infant with suprasystemic pulmonary hypertension, pulmonary capillary hemangiomatosis, and isolated pulmonary vein stenosis

“…Generally, most antihypertensive PH-targeted drugs (except sildenafil and bosentan) are applied off-label in children with PH (14). Approval of PH-targeted drugs is limited mainly due to a lack of studies on the use of these drugs, especially in younger children and infants.…”

“…Currently, many drugs with different routes of administration and targeted pathways are used to reduce PVR and consequently pressure overload on the RV, mainly by pulmonary vasodilatation (and anti-inflammation, anti-proliferation): phosphodiesterase-5 (PDE5) inhibitors (sildenafil), endothelinreceptor-antagonists (ERA) (macitentan, bosentan), soluble guanylate cyclase (sGC) stimulators (riociguat), prostacyclin agonists/analogues/mimetics (treprostinil, iloprost, epoprostenol, selexipag) (8). The majority of aformentioned PAH-targeted drugs, including selexipag are currently used off-label in children with PH in expert centers (14). Selexipag is the first orally administered selective prostacyclin receptor (IP) agonist that has been shown to induce vasodilation and to inhibit pulmonary (peri)vascular inflammation andproliferation.…”