Riociguat treatment in patients with pulmonary arterial hypertension: Final safety data from the EXPERT registry,Respiratory Medicine

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Riociguat treatment in patients with pulmonary arterial hypertension: Final safety data from the EXPERT registry
Respiratory Medicine ( IF 3.5 ) Pub Date : 2020-12-03 , DOI: 10.1016/j.rmed.2020.106241
Marius M Hoeper ₁ , Miguel-Angel Gomez Sanchez ₂ , Marc Humbert ₃ , David Pittrow ₄ , Gérald Simonneau ₅ , Henning Gall ₆ , Ekkehard Grünig ₇ , Hans Klose ₈ , Michael Halank ₉ , David Langleben ₁₀ , Repke J Snijder ₁₁ , Pilar Escribano Subias ₁₂ , Lisa M Mielniczuk ₁₃ , Tobias J Lange ₁₄ , Jean-Luc Vachiéry ₁₅ , Hubert Wirtz ₁₆ , Douglas S Helmersen ₁₇ , Iraklis Tsangaris ₁₈ , Joan A Barberà ₁₉ , Joanna Pepke-Zaba ₂₀ , Anco Boonstra ₂₁ , Stephan Rosenkranz ₂₂ , Silvia Ulrich ₂₃ , Regina Steringer-Mascherbauer ₂₄ , Marion Delcroix ₂₅ , Pavel Jansa ₂₆ , Iveta Šimková ₂₇ , George Giannakoulas ₂₈ , Jens Klotsche ₂₉ , Evgenia Williams ₃₀ , Christian Meier ₃₀ , Hossein-Ardeschir Ghofrani ₆ ,

Affiliation

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.
Université Paris-Saclay, Inserm U999, Service de Pneumologie et Soins Intensifs Respiratoires, Hôpital Bicêtre, Le Kremlin-Bicêtre, France.
Institute for Clinical Pharmacology, Technical University, Dresden, Germany.
Université Paris-Sud, Le Kremlin-Bicêtre, Service de Pneumologie, Centre de Référence de l'Hypertension Pulmonaire Sévère, DHU Thorax Innovation, Hôpital Bicêtre, Le Kremlin-Bicêtre, Paris, France.
University of Giessen and Marburg Lung Center (UGMLC), Giessen, Germany; Member of the German Center for Lung Research (DZL), Germany.
Centre for Pulmonary Hypertension, Thoraxclinic at Heidelberg University Hospital, Heidelberg, Germany.
Department of Pneumology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Medical Clinic I, Department of Pneumology, University Hospital Carl Gustav Carus, Dresden, Germany.
Center for Pulmonary Vascular Disease, Jewish General Hospital, McGill University, Montreal, Quebec, Canada.
Department of Pulmonology, St Antonius Ziekenhuis, Nieuwegein, the Netherlands.
Department of Cardiology, Hospital 12 de Octubre, CIBER-CV (CIBER of Cardiovascular Disease), Madrid, Spain.
Division of Cardiology, Department of Medicine, University of Ottawa Heart Institute, Ottawa, Ontario, Canada.
Department of Internal Medicine II, Division of Pneumology, University Medical Center, Regensburg, Germany.
Département de Cardiologie, Cliniques Universitaires de Bruxelles, Hôpital Erasme, Brussels, Belgium.
Department of Respiratory Medicine, University of Leipzig, Leipzig, Germany.
Alberta Health Services, University of Calgary, Calgary, Alberta, Canada.
Second Department of Critical Care, University Hospital Attikon, National and Kapodistrian University of Athens, Athens, Greece.
Hospital Clínic-IDIBAPS, University of Barcelona, Barcelona, Spain; Biomedical Research Networking Center on Respiratory Diseases (CIBERES), Madrid, Spain.
Pulmonary Vascular Disease Unit, Royal Papworth Hospital, Cambridge, UK.
VU Medisch Centrum, Amsterdam, the Netherlands.
Department III of Internal Medicine and Cologne Cardiovascular Research Center (CCRC), Cologne University Heart Center, Cologne, Germany.
Clinic of Pulmonology, University Hospital Zurich, Zurich, Switzerland.
Servicestelle für Klinische Studien, Krankenhaus der Elisabethinen Linz GmbH, Linz, Austria.
Clinical Department of Respiratory Diseases, University Hospitals and Laboratory of Respiratory Diseases & Thoracic Surgery (BREATHE), Department of Chronic Diseases & Metabolism (CHROMETA), KU Leuven - University of Leuven, Leuven, Belgium.
2(nd) Department of Medicine-Department of Cardiovascular Medicine, Charles University in Prague, Prague, Czech Republic.
Department of Cardiology and Angiology, Faculty of Medicine, Slovak Medical University & National Institute of Cardiovascular Diseases, Bratislava, Slovak Republic.
Department of Cardiology I, Aristotle University of Thessaloniki, Thessaloniki, Greece.
German Rheumatism Research Center Berlin, Leibniz Institute, Berlin, Germany.
Bayer AG, Global Development, Global Medical Affairs, Berlin, Germany.

Objective

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.

Methods

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.

Results

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.

Conclusion

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.

中文翻译：

利奥西呱治疗肺动脉高压患者：来自 EXPERT 登记处的最终安全性数据

客观的

经过 3 期随机试验，可溶性鸟苷酸环化酶刺激剂利奥西呱被批准用于治疗患有肺动脉高压 (PAH) 和无法手术或持续/复发性慢性血栓栓塞性肺动脉高压的成年患者。EXPosurE注册利奥西呱在肺动脉高压患者中的研究（EXPERT）旨在监测利奥西呱在临床实践中的长期安全性。

方法

EXPERT 是一项针对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。自入组起或停止利奥西呱治疗后 30 天，对患者进行至少 1 年、最长 4 年的随访。主要安全性结局是使用监管活动医学词典首选术语和系统器官分类 21.0 版编码的不良事件 (AE) 和严重不良事件 (SAE)，在常规临床就诊期间（通常每 3-6 个月）收集并通过病例报告进行整理形式。

结果

分析中总共纳入了 326 名 PAH 患者。这些患者中最常见的 AE 是头晕（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 是右心室/心力衰竭 (10.1%)、肺炎 (6.1%)、呼吸困难 (4.0%) 和晕厥 (3.4%)。咯血/肺出血的暴露调整率为每 100 患者年 2.5 次。