Alma Mater Studiorum, University of Bologna and IRCCS-S.Orsola University Hospital, Via Massarenti, 9, 40138, Bologna, Italy.
Mater Misericordiae University Hospital, Dublin, Ireland.
Adv Ther. 2022 Jan;39(1):796-810. doi: 10.1007/s12325-021-01898-1. Epub 2021 Oct 30.
In the event-driven GRIPHON randomised-controlled trial, the oral prostacyclin receptor agonist selexipag significantly reduced the risk of disease progression (composite primary endpoint of morbidity/mortality), compared with placebo, in patients with pulmonary arterial hypertension (PAH). The ongoing open-label extension study (GRIPHON OL) collects further data on long-term safety, tolerability, and survival of PAH patients treated with selexipag.
Patients randomised to selexipag or placebo in GRIPHON could enter GRIPHON OL either after experiencing a morbidity event during double-blind treatment or at the end of the study. Patients were followed for adverse events (AE) and survival from selexipag initiation up to 3 days and 30 days after end of treatment, respectively. Data are presented up to a cut-off date of 1 September 2019.
Overall, 953 patients in GRIPHON and GRIPHON OL were treated with selexipag. At the time of selexipag initiation, 81.2% of patients were receiving background PAH therapy. Median (min, max) exposure to selexipag was 31.7 months (0, 106), corresponding to a total of 3054.4 patient-years. The most frequently reported AEs were related to known prostacyclin-related effects or underlying disease. There were 305 (32.0%) patients who experienced an AE leading to treatment discontinuation. Survival during GRIPHON and GRIPHON OL was assessed for the 574 patients randomised to selexipag in GRIPHON. Kaplan-Meier survival estimates (95%CI) at 1, 3, 5 and 7 years were 92.0% (89.4, 94.0), 79.3% (75.4, 82.6), 71.2% (66.5, 75.3) and 63.0% (57.4, 68.1), respectively.
These results provide the longest follow-up period published to date for a PAH therapy. The safety profile of selexipag over this extended treatment period was consistent with that observed in GRIPHON. A large proportion of the population was receiving background therapy at selexipag initiation, providing further insight into the long-term safety of selexipag as part of a combination therapy regimen.
ClinicalTrials.gov Identifiers: NCT01106014 and NCT01112306.
在事件驱动的 GRIPHON 随机对照试验中，与安慰剂相比，口服前列环素受体激动剂塞来昔帕显著降低了肺动脉高压（PAH）患者的疾病进展风险（发病率/死亡率复合主要终点）。正在进行的开放标签扩展研究（GRIPHON OL）收集了更多关于塞来昔帕治疗 PAH 患者的长期安全性、耐受性和生存数据。
在 GRIPHON 中随机分配至塞来昔帕或安慰剂的患者，在双盲治疗期间出现发病率事件或研究结束后，可以进入 GRIPHON OL。从塞来昔帕起始开始，分别对患者进行不良事件（AE）和生存随访，随访时间分别为 3 天和治疗结束后 30 天。数据截止日期为 2019 年 9 月 1 日。
在 GRIPHON 和 GRIPHON OL 中，共有 953 例患者接受了塞来昔帕治疗。在开始塞来昔帕治疗时，81.2%的患者正在接受背景 PAH 治疗。塞来昔帕中位（最小，最大）暴露时间为 31.7 个月（0，106），总共有 3054.4 患者-年。最常报告的 AE 与已知的前列环素相关作用或基础疾病有关。有 305 例（32.0%）患者因 AE 导致治疗中断。GRIPHON 和 GRIPHON OL 中对随机分配至塞来昔帕的 574 例患者进行了生存评估。Kaplan-Meier 生存估计（95%CI）在 1、3、5 和 7 年时分别为 92.0%（89.4，94.0）、79.3%（75.4，82.6）、71.2%（66.5，75.3）和 63.0%（57.4，68.1）。
这些结果提供了迄今为止最长的 PAH 治疗随访期。在延长的治疗期间，塞来昔帕的安全性与在 GRIPHON 中观察到的一致。在开始塞来昔帕治疗时，很大一部分人群正在接受背景治疗，这进一步深入了解了塞来昔帕作为联合治疗方案的长期安全性。
ClinicalTrials.gov 标识符：NCT01106014 和 NCT01112306。
