Youssef David, Richards Susan, Lague Sabine, Sheppard Catherine, Smith Jenna, Vorhies Erika, Hosking Martin, Pietrosanu Matthew, Bates Angela
Department of Pediatric Pulmonary Hypertension, Stollery Children's Hospital, Edmonton, AB, Canada.
Department of Pediatrics, BC Children's Hospital, Vancouver, BC, Canada.
Front Pediatr. 2023 Feb 28;11:1055158. doi: 10.3389/fped.2023.1055158. eCollection 2023.
Selexipag, an oral nonprostanoid prostaglandin receptor agonist, has led to reduced morbidity and mortality in adults with pulmonary arterial hypertension (PAH). While the adult literature has been extrapolated to suggest selexipag as an oral treatment for severe pediatric pulmonary hypertension (PH), longitudinal, multicenter data on the benefits of selexipag in this population are lacking. The purpose of this study is to present a longitudinal, multicentre experience with selexipag in a relatively large cohort of pediatric PH patients and add to the existing selexipag literature.
We performed a retrospective, multicenter review describing the clinical outcomes of pediatric PH patients receiving selexipag in addition to standard oral pulmonary vasodilator therapy across three Canadian centers between January 2005 and June 2021.
Twenty-four pediatric patients (fifteen female) with a mean age of 9.7 (range 2.0-15.5) years were included. Of this cohort, eighteen (75.0%) were in group 1, one (4.2%) was in group 2, four (16.7%) were in group 3, and one (4.2%) was in group 4. Twenty-two (91.7%) patients were on dual PH therapy after six months. Dosing was targeted to achieve 20-30 mcg/kg/dose orally every twelve hours. Median dose after twelve months was 30 mcg/kg/dose. Twelve months following selexipag initiation, median decreases of 0.2 cm in tricuspid annular plane systolic excursion, 3.5 mmHg in right-ventricular systolic pressure, and 6.1 mmHg in mean pulmonary arterial pressure were observed; none of these changes were statistically significant. Three patients died, one clinically deteriorated and required admission to a pediatric intensive care unit, ten had gastrointestinal symptoms, and three had flushing.
Selexipag appears to be a safe and effective adjunctive therapy for pediatric PH patients and has a tolerable adverse effect profile aside from gastrointestinal disturbances. Additional prospective studies of changes in hemodynamics and functional classification over a longer period and with a larger sample are needed. Future research should aim to identify subgroups that stand to benefit from the addition of selexipag as well as optimal timing and dosing for the pediatric population.
司来帕格是一种口服非前列腺素类前列腺素受体激动剂，已降低了成人肺动脉高压（PAH）的发病率和死亡率。虽然已有成人文献推断司来帕格可作为重度小儿肺动脉高压（PH）的口服治疗药物，但缺乏关于司来帕格在该人群中获益情况的纵向多中心数据。本研究的目的是介绍在相对较大队列的小儿PH患者中使用司来帕格的纵向多中心经验，并补充现有的司来帕格相关文献。
我们进行了一项回顾性多中心综述，描述了2005年1月至2021年6月期间加拿大三个中心接受司来帕格治疗的小儿PH患者的临床结局，这些患者同时接受标准口服肺血管扩张剂治疗。
纳入了24例小儿患者（15例女性），平均年龄为9.7岁（范围2.0 - 15.5岁）。在该队列中，18例（75.0%）属于1组，1例（4.2%）属于2组，4例（16.7%）属于3组，1例（4.2%）属于4组。22例（91.7%）患者在6个月后接受双重PH治疗。给药目标是每12小时口服20 - 30微克/千克/剂量。12个月后的中位剂量为30微克/千克/剂量。开始使用司来帕格12个月后，观察到三尖瓣环平面收缩期位移中位数下降0.2厘米，右心室收缩压下降3.5毫米汞柱，平均肺动脉压下降6.1毫米汞柱；这些变化均无统计学意义。3例患者死亡，1例临床病情恶化并需要入住儿科重症监护病房，10例有胃肠道症状，3例有潮红症状。
司来帕格似乎是小儿PH患者安全有效的辅助治疗药物，除胃肠道不适外，不良反应可耐受。需要进行更多关于更长时间和更大样本量的血流动力学和功能分级变化的前瞻性研究。未来的研究应旨在确定可能从添加司来帕格中获益的亚组，以及针对小儿人群的最佳给药时机和剂量。
