Clinical efficacy and safety of selexipag in children and young adults with idiopathic and heritable pulmonary arterial hypertension

Abstract

Objective: This study aimed to investigate the safety, tolerability, and efficacy of selexipag in children and young adults with idiopathic and heritable pulmonary arterial hypertension. Methods: This retrospective cohort study included clinical data from five children and six young adults with pulmonary arterial hypertension receiving selexipag as add-on therapy or as a transition from beraprost sodium or epoprostenol infusion therapy. Clinical efficacy was evaluated by measuring improvement in clinical variables from baseline, including hemodynamic parameters. Results: Of the 11 patients, 6 were switched from beraprost sodium to selexipag and one paediatric patient transitioned from epoprostenol to selexipag. The median maintenance dose of selexipag in children was 80 μg/kg/day. In nine patients undergoing repeat catheterisation, statistically significant improvements were observed after the initiation of selexipag in terms of mean pulmonary arterial pressure (p < 0.01), pulmonary vascular resistance index (p < 0.05), and cardiac index (p < 0.01). None of the patients had clinical worsening after selexipag during follow-up, but one young adult patient discontinued treatment due to severe headache. The most common side effect profiles were headache, nausea, abdominal pain, jaw pain, myalgia, and diarrhoea. Conclusions: Selexipag may have a favourable safety profile and potential efficacy in children and young adults with pulmonary arterial hypertension.

Hemodynamic assessment of transitioning from parenteral prostacyclin to selexipag in pediatric pulmonary hypertension

“…Available data are limited by the small number of patients, lack of hemodynamic confirmation, long‐term follow‐up, and sparse pediatric data. 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 The largest series to date is presented by Frost et al In this series the authors present 34 adult patients that underwent a transition from inhaled treprostinil to oral selexipag with successful transition in 32 patients (94%) as assessed by changes in functional class, BNP, and 6MWT over a 16‐week period. No hemodynamic assessments were made, and these patients were long‐term survivors with a mean time from diagnosis to transition of 8 years.…”

“… 9 , 10 Despite its increasing use in both the adult and pediatric PAH populations, there is limited data on the hemodynamic efficacy of transitioning from parenteral prostacyclins to selexipag, particularly in the pediatric population. 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 Therefore, the objective of this study was to characterize the hemodynamic changes associated with transitioning from parenteral prostacyclins to enteral selexipag in children. To this end, we retrospectively collected hemodynamic data from 11 children who had undergone a transition from parenteral prostacyclin ( n = 7 SC treprostinil; n = 1 IV treprostinil; and n = 3 inhaled tyvaso) to enteral selexipag from October 2016 to May 2022.…”

“…9,10 Despite its increasing use in both the adult and pediatric PAH populations, there is limited data on the hemodynamic efficacy of transitioning from parenteral prostacyclins to selexipag, particularly in the pediatric population. [11][12][13][14][15][16][17][18][19][20] Therefore, the objective of this study was to characterize the hemodynamic changes associated with transitioning from parenteral prostacyclins to enteral selexipag in children.…”

“…Following large, randomized trials in adult PAH that demonstrated a significant decrease in mortality and PAH complications, selexipag (Uptravi®) was approved for the treatment of adults with PAH in 2015 9,10 . Despite its increasing use in both the adult and pediatric PAH populations, there is limited data on the hemodynamic efficacy of transitioning from parenteral prostacyclins to selexipag, particularly in the pediatric population 11–20 . Therefore, the objective of this study was to characterize the hemodynamic changes associated with transitioning from parenteral prostacyclins to enteral selexipag in children.…”

Switching from Beraprost to Selexipag in the Treatment of Pulmonary Arterial Hypertension: Insights from a Phase IV Study of the Japanese Registry (The EXCEL Study: EXChange from bEraprost to seLexipag Study)

“…However, data on the safety and efficacy of this approach are limited. A recent retrospective study suggested that switching from beraprost to selexipag may be safe and effective in children and young adults with idiopathic and heritable PAH [17]. To our knowledge, no prospective studies have evaluated the outcomes of transitioning from beraprost to selexipag in a multicenter setting.…”