Riociguat for the treatment of pulmonary arterial hypertension associated with connective tissue disease: results from PATENT-1 and PATENT-2.
Riociguat for the treatment of pulmonary arterial hypertension associated with connective tissue disease: results from PATENT-1 and PATENT-2.
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DOI：
10.1136/annrheumdis-2015-209087
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发表时间：
2017-02
影响因子：
27.4
通讯作者：
Denton CP
中科院分区：
文献类型：
--
作者：
Humbert M;Coghlan JG;Ghofrani HA;Grimminger F;He JG;Riemekasten G;Vizza CD;Boeckenhoff A;Meier C;de Oliveira Pena J;Denton CP
为期12周的III期肺动脉高压sGC刺激试验（PATENT）-1研究在肺动脉高压（PAH）患者中研究了利奥西呱。在此，我们对利奥西呱在结缔组织病相关PAH（PAH-CTD）患者亚组中的安全性和疗效进行了前瞻性分析。PAH-CTD患者事后被进一步分类为PAH伴系统性硬化症或PAH-其他定义的CTD。在PATENT-1中，患者接受利奥西呱（最大2.5或1.5 mg，每日三次）或安慰剂。 疗效终点包括6分钟步行距离（6 MWD;主要终点）、血流动力学和WHO功能分级（WHO FC）较基线的变化。在长期扩展PATENT-2中，患者接受利奥西呱（最大剂量2.5 mg，每日三次）;主要终点为安全性和耐受性。 在PAH-CTD患者中，利奥西呱增加了平均6 MWD、WHO FC、肺血管阻力和心脏指数。6 MWD和WHO FC的改善持续2年。 PAH-CTD患者的2年生存率与特发性PAH相同（93%）。利奥西瓜在PAH-CTD患者中的安全性特征与总体人群相似。Riociguat耐受性良好，与PAH-CTD患者中持续2年的6 MWD和其他终点的积极趋势相关。 专利-1（NCT 00810693）、专利-2（NCT 00863681）。
The 12-week, phase III Pulmonary Arterial hyperTENsion sGC-stimulator Trial (PATENT)-1 study investigated riociguat in patients with pulmonary arterial hypertension (PAH). Here, we present a prospectively planned analysis of the safety and efficacy of riociguat in the subgroup of patients with PAH associated with connective tissue disease (PAH-CTD). Patients with PAH-CTD were further classified post hoc as having PAH associated with systemic sclerosis or PAH-other defined CTD. In PATENT-1, patients received riociguat (maximum 2.5 or 1.5 mg three times daily) or placebo. Efficacy endpoints included change from baseline in 6-minute walking distance (6MWD; primary endpoint), haemodynamics and WHO functional class (WHO FC). In the long-term extension PATENT-2, patients received riociguat (maximum 2.5 mg three times daily); the primary endpoint was safety and tolerability. In patients with PAH-CTD, riociguat increased mean 6MWD, WHO FC, pulmonary vascular resistance and cardiac index. Improvements in 6MWD and WHO FC persisted at 2 years. Two-year survival of patients with PAH-CTD was the same as for idiopathic PAH (93%). Riociguat had a similar safety profile in patients with PAH-CTD to that of the overall population. Riociguat was well tolerated and associated with positive trends in 6MWD and other endpoints that were sustained at 2 years in patients with PAH-CTD. PATENT-1 (NCT00810693), PATENT-2 (NCT00863681).