Pulmonary, Critical Care, and Sleep Division, Tufts Medical Center, Boston, Massachusetts.
Pulmonary and Critical Care, Massachusetts General Hospital, Boston, Massachusetts.
J Heart Lung Transplant. 2018 Mar;37(3):401-408. doi: 10.1016/j.healun.2017.09.024. Epub 2017 Oct 2.
Parenteral prostacyclin analogs that target the prostacyclin pathway have been used to treat pulmonary arterial hypertension (PAH) since the 1990s. Abrupt discontinuation of parenteral prostacyclin analogs can be associated with acute deterioration of PAH. Less is known about temporary interruption of oral therapies that target the prostacyclin pathway, such as selexipag.
We evaluated the frequency, duration, reasons, and consequences of temporary selexipag interruptions among PAH patients enrolled in the Prostacyclin (PGI) Receptor Agonist in Pulmonary Arterial Hypertension (GRIPHON) study. In GRIPHON, patients were randomized to selexipag or placebo and titrated to an individualized highest tolerated dose (200 to 1,600 µg twice daily) over 12 weeks, after which patients entered the maintenance phase. Treatment interruptions were allowed; if the interruption was < 3 days, treatment was restarted at the previous highest tolerated dose; if the interruption was ≥ 3 days, retitration from 200 µg twice daily was required. Descriptive analyses were performed.
At least 1 treatment interruption occurred in 111 of 574 patients (19.3%) in the selexipag group and in 58 of 582 (10.0%) in the placebo group. Baseline characteristics were similar between patients with and without an interruption. Of the 111 patients in whom selexipag was temporarily interrupted, 94 (85%) were receiving background PAH therapy. Adverse events were the most common reason for selexipag interruption. Selexipag interruptions and reinstitution of treatment were well tolerated. There were no episodes of acute deterioration during treatment interruption.
Based on observations from GRIPHON, selexipag interruptions can be expected in clinical practice. However, temporarily interrupting selexipag was well tolerated and manageable.
自 20 世纪 90 年代以来，靶向前列环素途径的肠外前列环素类似物已被用于治疗肺动脉高压（PAH）。突然停止肠外前列环素类似物的治疗可能会导致 PAH 急剧恶化。对于靶向前列环素途径的口服治疗药物（如塞来昔帕）的临时中断，人们了解较少。
我们评估了在参与前列环素（PGI）受体激动剂治疗肺动脉高压（GRIPHON）研究的 PAH 患者中，塞来昔帕临时中断的频率、持续时间、原因和后果。在 GRIPHON 研究中，患者被随机分配至塞来昔帕或安慰剂组，并在 12 周内滴定至个体化最高耐受剂量（200 至 1600μg，每日两次），之后患者进入维持阶段。允许中断治疗；如果中断时间<3 天，则以之前的最高耐受剂量重新开始治疗；如果中断时间≥3 天，则需要从 200μg，每日两次重新滴定。进行描述性分析。
在塞来昔帕组的 574 例患者中（19.3%）和安慰剂组的 582 例患者中（10.0%）至少发生了 1 次治疗中断。中断治疗和未中断治疗的患者的基线特征相似。在塞来昔帕临时中断的 111 例患者中，94 例（85%）正在接受背景 PAH 治疗。不良事件是塞来昔帕中断的最常见原因。塞来昔帕中断和重新开始治疗均耐受良好。在治疗中断期间没有发生急性恶化的情况。
基于 GRIPHON 的观察结果，预计在临床实践中会出现塞来昔帕的中断。然而，临时中断塞来昔帕是可以耐受和管理的。
