Selexipag for the Treatment of Pediatric Pulmonary Hypertension: A Systematic Review

To systematically evaluate the safety, dosing regimen, and efficacy of selexipag for pediatric patients with pulmonary hypertension (PH).A literature search of the electronic databases of PubMed, Embase, Web of Science, Cochrane Library, and Google Scholar was performed from inception through February 28, 2023. Two reviewers independently searched and evaluated the quality of the studies and pooled data when appropriate. Full-text articles of studies of children diagnosed with PH and treated with selexipag were eligible. Pediatric patients with PH were classified into 2 groups: the add-on therapy group, in which selexipag was used as a third therapy in addition to the baseline treatment, and the transition therapy group, in which patients were switched from parenteral prostacyclin analogs to selexipag.Fourteen studies involving 58 pediatric patients with PH were included. All studies were either case reports or case series. Overall, 30 and 28 patients were in the add-on and transition therapy groups, respectively. In both groups, selexipag was initially administered as 50-200 µg twice daily and titrated to a tolerated dosage of 200-1,600 µg twice daily. Prostacyclin analogs were simultaneously weaned for patients in the transition group. In the add-on therapy group, 16 patients (80.0%) were at low risk of the World Health Organization functional class (WHO FC I/II), 12 (76.9%) were at low risk of the 6-minute walk distance (6MWD; >350 m), and 21 (95.5%) were at low risk of the pulmonary vascular resistance index (PVRi; <20 WU/m2). Furthermore, N-terminal pro-brain natriuretic peptide and mean pulmonary arterial pressure were significantly improved. More than 70% of patients experienced common tolerable side effects, such as headache, nausea, and diarrhea. In the transition therapy group, 5 patients (55.6%) were at low risk according to WHO FC I/II, 6 (66.7%) were at low risk according to 6MWD, and 14 (87.5) were at low risk according to PVRi; however, selexipag had no significant effect on their hemodynamic parameters. Additionally, more than 80% of patients experienced no side effects.Selexipag as add-on therapy or for transition from prostacyclin analogs may have a favorable safety profile and potential efficacy for pediatric patients with PH. Further high-quality evidence of the efficacy and safety of selexipag for the treatment of pediatric PH is warranted.