Hoeper Marius M, Gomez Sanchez Miguel-Angel, Humbert Marc, Pittrow David, Simonneau Gérald, Gall Henning, Grünig Ekkehard, Klose Hans, Halank Michael, Langleben David, Snijder Repke J, Escribano Subias Pilar, Mielniczuk Lisa M, Lange Tobias J, Vachiéry Jean-Luc, Wirtz Hubert, Helmersen Douglas S, Tsangaris Iraklis, Barberà Joan A, Pepke-Zaba Joanna, Boonstra Anco, Rosenkranz Stephan, Ulrich Silvia, Steringer-Mascherbauer Regina, Delcroix Marion, Jansa Pavel, Šimková Iveta, Giannakoulas George, Klotsche Jens, Williams Evgenia, Meier Christian, Ghofrani Hossein-Ardeschir
Department of Respiratory Medicine and the German Center for Lung Research, Hannover Medical School, Hannover, Germany.
Respiratory Department, Ramón y Cajal University Hospital (IRYCIS), Biomedical Research Networking Center on Respiratory Diseases (CIBERES), Madrid, Spain.
Respir Med. 2021 Feb;177:106241. doi: 10.1016/j.rmed.2020.106241. Epub 2020 Dec 3.
The soluble guanylate cyclase stimulator riociguat is approved for the treatment of adult patients with pulmonary arterial hypertension (PAH) and inoperable or persistent/recurrent chronic thromboembolic pulmonary hypertension following Phase 3 randomized trials. The EXPosurE Registry RiociguaT in patients with pulmonary hypertension (EXPERT) study was designed to monitor the long-term safety of riociguat in clinical practice.
EXPERT was an international, multicenter, prospective, uncontrolled, non-interventional cohort study of patients treated with riociguat. Patients were followed for at least 1 year and up to 4 years from enrollment or until 30 days after stopping riociguat treatment. Primary safety outcomes were adverse events (AEs) and serious adverse events (SAEs) coded using Medical Dictionary for Regulatory Activities preferred terms and System Organ Classes version 21.0, collected during routine clinic visits (usually every 3-6 months) and collated via case report forms.
In total, 326 patients with PAH were included in the analysis. The most common AEs in these patients were dizziness (11.7%), right ventricular (RV)/cardiac failure (10.7%), edema/peripheral edema (10.7%), diarrhea (8.6%), dyspnea (8.0%), and cough (7.7%). The most common SAEs were RV/cardiac failure (10.1%), pneumonia (6.1%), dyspnea (4.0%), and syncope (3.4%). The exposure-adjusted rate of hemoptysis/pulmonary hemorrhage was 2.5 events per 100 patient-years.
Final data from EXPERT show that in patients with PAH, the safety of riociguat in clinical practice was consistent with clinical trials, with no new safety concerns identified and a lower exposure-adjusted rate of hemoptysis/pulmonary hemorrhage than in the long-term extension of the Phase 3 trial in PAH.
可溶性鸟苷酸环化酶刺激剂利奥西呱在3期随机试验后被批准用于治疗成年肺动脉高压(PAH)患者以及无法手术或持续性/复发性慢性血栓栓塞性肺动脉高压患者。肺动脉高压患者利奥西呱暴露登记研究(EXPERT)旨在监测利奥西呱在临床实践中的长期安全性。
EXPERT是一项针对接受利奥西呱治疗患者的国际、多中心、前瞻性、非对照、非干预性队列研究。患者从入组开始随访至少1年,最长4年,或直至停止利奥西呱治疗后30天。主要安全性结局为不良事件(AE)和严重不良事件(SAE),使用《监管活动医学词典》首选术语和系统器官分类第21.0版进行编码,在常规门诊就诊(通常每3 - 6个月一次)时收集,并通过病例报告表进行整理。
总共326例PAH患者纳入分析。这些患者中最常见的AE为头晕(11.7%)、右心室(RV)/心力衰竭(10.7%)、水肿/外周水肿(10.7%)、腹泻(8.6%)、呼吸困难(8.0%)和咳嗽(7.7%)。最常见的SAE为RV/心力衰竭(10.1%)、肺炎(6.1%)、呼吸困难(4.0%)和晕厥(3.4%)。咯血/肺出血的暴露调整发生率为每100患者年2.5次事件。
EXPERT的最终数据表明,在PAH患者中,利奥西呱在临床实践中的安全性与临床试验一致,未发现新的安全问题,且咯血/肺出血的暴露调整发生率低于PAH 3期试验的长期延长期。