Selexipag well tolerated, safe in children with PAH

Use of oral add-on selexipag in children was well tolerated, safe and improved pulmonary arterial hypertension outcomes, according to data published in The Journal of Heart and Lung Transplantation.

Researchers found that selexipag treatment was linked to improvement in invasive hemodynamics, right ventricular systolic function, functional class, European Pediatric Pulmonary Vascular Disease Network (EPPVDN) pediatric pulmonary hypertension prognostic risk score and a trend toward lower serum N-terminal pro-B-type natriuretic peptide (NT-proBNP) concentrations, Georg Hansmann, MD, PhD, staff pediatric cardiologist, physician scientist and director of the Pediatric Pulmonary Hypertension Program in the department of pediatric cardiology and critical care at Hannover Medical School, Germany, and colleagues wrote.

Selexipag (Uptravi, Actelion), an oral prostacyclin receptor agonist, was administered to 15 children with PAH at three centers in Hannover, Germany. Most patients underwent cardiac catherization at baseline and at 8-month follow-up.

There were no deaths related to oral add-on selexipag treatment, according to the results. Two patients underwent lung transplantation and one patient died while receiving IV treprostinil.

In 10 patients, the researchers reported improvement in mean right atrial pressure (–2 mm Hg), ratio of pulmonary arterial pressure to systemic arterial pressure (mean and diastolic, –17%) and mean transpulmonary pressure gradient (–17%; P < .01) and diastolic transpulmonary pressure gradient (–6 mm Hg; P < .05) after selexipag therapy at 5 to 18 months of follow-up compared with baseline. At follow-up, patients who received selexipag had a lower pulmonary vascular resistance index (–13%; P = .131) and pulmonary vascular resistance to systemic vascular resistance ratio (–20%; P = .097) and a higher cardiac index (+18%; P = .322), according to the results.

Add-on selexipag was also associated with improved right ventricular systolic function (P < .01) and functional class. Six-minute walk distance “varied greatly” among the patients and was not significantly different after selexipag treatment at follow-up compared with baseline. According to the researchers, this finding confirms that 6-minute walk distance “is not always a good indicator of exercise capacity, at least in children.” In addition, serum NT-proBNP varied greatly and improved in half of the patients (–24.7%; P = .277).

The researchers applied, for the first time, the 2019 EPPVDN pediatric pulmonary hypertension risk scores in a prospective analysis of a pediatric cohort. Noninvasive and combined invasive and noninvasive pulmonary hypertension risk scores improved after selexipag therapy (P < .05).

“Taken together, our data show that the new EPPVDN risk score, be it combined invasive/noninvasive or noninvasive only, can reliably indicate a change of clinical status with medication and can reliably determine the risk when compared with the established single determinants of risk and outcome,” Hansmann and colleagues wrote.

Overall, oral selexipag in children with PAH improved several outcome-relevant variables in 50% of patients, prevented disease progression in 27%, and 20% of patients deteriorated during the observation period.

Selexipag was well tolerated overall, with no discontinuations related to adverse events. The most common adverse events were nausea (n = 7), headache (n = 6) and vomiting (n = 1). Pain in the jaw (n = 2) or extremities (n = 1) occurred less frequently in this cohort compared with adults in the GRIPHON trial, according to the researchers.

“Oral add-on therapy with selexipag in children with PAH, although not approved in this age group to date, is well tolerated and appears to be safe when closely monitored,” the researchers wrote. “It may, thus, be useful in the clinical follow-up but needs to be validated in larger prospective PAH studies to elucidate its broader applicability and usefulness in clinical care.”