在SERAPHIN,一个长期的,事件驱动,肺动脉高压(PAH)的双盲随机对照试验,与安慰剂相比,马西坦10mg显著降低了发病/死亡风险.其开放标签延伸研究(SERAPHINOL)进一步评估了10mg马西坦在PAH患者中的长期安全性和耐受性。
在研究期间完成双盲治疗期或经历发病事件的SERAPHIN患者可进入SERAPHINOL。患者每天一次接受10毫克的Macitentan,评估安全性和生存率直至治疗结束(+28天).分析了两组重叠的安全性:(1)所有患者在SERAPHINOL(OL安全组)中;(2)患者随机接受10mg在SERAPHIN(长期安全性/生存组)。生存率作为后一组中的探索性终点进行评估。
在742名随机接受SERAPHIN的患者中,550例(74.1%)进入了SERAPHINOL(OL安全组);242例患者被随机分配接受10mgSERAPHIN(长期安全性/生存组)。中位数(最小值,max)10mg马西坦暴露量为40.1(0.1,130.5)个月(2074.7患者年;OL安全性集)和54.7(0.1,141.3)个月(1151.0患者年;长期安全性/生存集).两个分析集中的安全性与Macitentan的已知安全性相当。Kaplan-Meier在1、5、7和9年的生存率估计(95%CI)为95.0%(91.3、97.1),73.3%(66.6,78.9),62.6%(54.6,69.6)和52.7%(43.6,61.0),分别(长期安全性/生存集;中位随访时间:5.9年)。
该分析提供了迄今为止发表的任何PAH疗法的最长安全性和生存率随访。在这一广泛的治疗期间,10mg马刺坦的安全性与SERAPHIN中观察到的一致。由于大多数患者在马西坦开始时接受其他PAH治疗,我们的研究为Macitentan的长期安全性提供了更多的见解,包括作为联合治疗的一部分。
ClinicalTrials.gov标识符:NCT00660179和NCT00667823。
In SERAPHIN, a long-term, event-driven, double-blind randomised controlled trial in pulmonary arterial hypertension (PAH), macitentan 10 mg significantly reduced the risk of morbidity/mortality compared with placebo. Its open-label extension study (SERAPHIN OL) further assessed long-term safety and tolerability of macitentan 10 mg in PAH patients.
Patients in SERAPHIN who completed the double-blind treatment period or experienced a morbidity event during the study could enter SERAPHIN OL. Patients received macitentan 10 mg once daily, and safety and survival were assessed until end of treatment (+ 28 days). Two overlapping sets were analysed for safety: (1) all patients in SERAPHIN OL (OL safety set); (2) patients randomised to macitentan 10 mg in SERAPHIN (long-term safety/survival set). Survival was evaluated as an exploratory endpoint in the latter set.
Of 742 patients randomised in SERAPHIN, 550 (74.1%) entered SERAPHIN OL (OL safety set); 242 patients were randomised to macitentan 10 mg in SERAPHIN (long-term safety/survival set). Median (min, max) exposure to macitentan 10 mg was 40.1 (0.1, 130.5) months (2074.7 patient-years; OL safety set) and 54.7 (0.1, 141.3) months (1151.0 patient-years; long-term safety/survival set). Safety in both analysis sets was comparable to the known safety profile of macitentan. Kaplan-Meier survival estimates (95% CI) at 1, 5, 7 and 9 years were 95.0% (91.3, 97.1), 73.3% (66.6, 78.9), 62.6% (54.6, 69.6) and 52.7% (43.6, 61.0), respectively (long-term safety/survival set; median follow-up: 5.9 years).
This analysis provides the longest follow-up for safety and survival published to date for any PAH therapy. The safety profile of macitentan 10 mg over this extensive treatment period was in line with that observed in SERAPHIN. As the majority of patients were receiving other PAH therapy at macitentan initiation, our study provides additional insight into the long-term safety of macitentan, including as part of combination therapy.
ClinicalTrials.gov Identifiers: NCT00660179 and NCT00667823.