Department of Respiratory Medicine, G. Papanikolaou Hospital , Thessaloniki, Greece.
Department of Respiratory Failure, Aristotle University of Thessaloniki , Thessaloniki, Greece.
Expert Opin Pharmacother. 2021 Jan;22(1):29-36. doi: 10.1080/14656566.2020.1812579. Epub 2020 Aug 31.
Selexipag is a first-in-class, oral, long-acting, selective, non-prostanoid agonist of the prostacyclin receptor (IP receptor), indicated for the treatment of symptomatic adult pulmonary arterial hypertension (PAH). It was designed with the objective to surpass the inconveniences associated with standard prostanoid therapy, presenting fewer adverse effects and comparable hemodynamic benefits.
This review describes the pharmacologic properties of selexipag and presents the clinical trials that have been completed or are currently ongoing regarding its clinical efficacy, safety, and tolerability. The pivotal GRIPHON study is extensively presented.
Selexipag is the first IP receptor to reduce the morbidity/mortality composite endpoint of the GRIPHON study, a large, randomized, placebo-controlled study. The TRITON study failed to demonstrate a clear benefit of initial triple oral therapy including selexipag compared to initial double oral therapy. Current guidelines do not provide definitive recommendations regarding the place of selexipag in the treatment algorithm of PAH. Finally, the possibility of transition between the several drugs acting in the prostacyclin pathway, and the potential role of selexipag in chronic thromboembolic pulmonary hypertension and pediatric PAH is currently being examined, possibly expanding its future use.
塞乐西帕是前列环素受体(IP 受体)的首个口服、长效、选择性非前列腺素激动剂,用于治疗有症状的成人肺动脉高压(PAH)。其设计目的是克服标准前列腺素治疗相关的不便,表现出更少的不良反应和相当的血液动力学益处。
本综述描述了塞乐西帕的药理学特性,并介绍了已完成或正在进行的关于其临床疗效、安全性和耐受性的临床试验。重点介绍了 GRIPHON 研究。
塞乐西帕是首个降低 GRIPHON 研究发病率/死亡率复合终点的 IP 受体,这是一项大型、随机、安慰剂对照研究。TRITON 研究未能证明初始三联口服治疗(包括塞乐西帕)与初始二联口服治疗相比有明显获益。目前的指南并未对塞乐西帕在 PAH 治疗方案中的地位提供明确建议。最后,正在研究几种作用于前列环素途径的药物之间的转换可能性,以及塞乐西帕在慢性血栓栓塞性肺动脉高压和儿科 PAH 中的潜在作用,可能会扩大其未来的应用。