Hossein-Ardeschir Ghofrani1, Miguel-Angel Gomez Sanchez2, Marc Humbert3, David Pittrow4, Gérald Simonneau5, Henning Gall6, Ekkehard Grünig7, Hans Klose8, Michael Halank9, David Langleben10, Repke J Snijder11, Pilar Escribano Subias12, Lisa M Mielniczuk13, Tobias J Lange14, Jean-Luc Vachiéry15, Hubert Wirtz16, Douglas S Helmersen17, Iraklis Tsangaris18, Joan A Barberá19, Joanna Pepke-Zaba20, Anco Boonstra21, Stephan Rosenkranz22, Silvia Ulrich23, Regina Steringer-Mascherbauer24, Marion Delcroix25, Pavel Jansa26, Iveta Šimková27, George Giannakoulas28, Jens Klotsche29, Evgenia Williams30, Christian Meier30, Marius M Hoeper31. 1. University of Giessen and Marburg Lung Center (UGMLC), Giessen, Germany; Member of the German Center for Lung Research (DZL), Giessen, Germany. Electronic address: Ardeschir.Ghofrani@innere.med.uni-giessen.de. 2. Respiratory Department, Ramón y Cajal University Hospital (IRYCIS), Madrid, Spain; Biomedical Research Networking Centre on Respiratory Diseases (CIBERES), Spain. 3. Université Paris-Saclay, Inserm U999, Service de Pneumologie et Soins Intensifs Respiratoires, Hôpital Bicêtre, Le Kremlin-Bicêtre, France. 4. Institute for Clinical Pharmacology, Technical University, Dresden, Germany. 5. 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. 6. University of Giessen and Marburg Lung Center (UGMLC), Giessen, Germany; Member of the German Center for Lung Research (DZL), Giessen, Germany. 7. Centre for Pulmonary Hypertension, Thoraxclinic at Heidelberg University Hospital, Heidelberg, Germany. 8. Department of Pneumology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. 9. Medical Clinic I, Department of Pneumology, University Hospital Carl Gustav Carus, Dresden, Germany. 10. Center for Pulmonary Vascular Disease, Jewish General Hospital, McGill University, Montreal, Quebec, Canada. 11. Department of Pulmonology, St Antonius Ziekenhuis, Nieuwegein, the Netherlands. 12. Department of Cardiology, Hospital 12 de Octubre, Madrid, Spain; CIBER-CV (CIBER of Cardiovascular Disease), Hospital 12 de Octubre, Madrid, Spain. 13. Division of Cardiology, Department of Medicine, University of Ottawa Heart Institute, Ottawa, Ontario, Canada. 14. Department of Internal Medicine II, Division of Pneumology, University Medical Center, Regensburg, Germany. 15. Département de Cardiologie, Cliniques Universitaires de Bruxelles, Hôpital Erasme, Brussels, Belgium. 16. Department of Respiratory Medicine, University of Leipzig, Leipzig, Germany. 17. Alberta Health Services, University of Calgary, Calgary, Alberta, Canada. 18. Second Department of Critical Care, University Hospital Attikon, National and Kapodistrian University of Athens, Athens, Greece. 19. Hospital Clínic-IDIBAPS, University of Barcelona, Barcelona, Spain; Biomedical Research Networking Center on Respiratory Diseases (CIBERES), Madrid, Spain. 20. Pulmonary Vascular Disease Unit, Royal Papworth Hospital, Cambridge, UK. 21. VU Medisch Centrum, Amsterdam, the Netherlands. 22. Department III of Internal Medicine and Cologne Cardiovascular Research Center (CCRC), Cologne University Heart Center, Cologne, Germany. 23. Clinic of Pulmonology, University Hospital Zurich, Zurich, Switzerland. 24. Servicestelle für klinische Studien, Krankenhaus der Elisabethinen Linz GmbH, Linz, Austria. 25. Department of Respiratory Diseases, University Hospitals of Leuven, and Respiratory Division, Department CHROMETA, KU Leuven - University of Leuven, Leuven, Belgium. 26. 2(nd) Department of Medicine, Department of Cardiovascular Medicine, Charles University in Prague, Prague, Czech Republic. 27. Department of Cardiology and Angiology, Faculty of Medicine, Slovak Medical University & National Institute of Cardiovascular Diseases, Bratislava, Slovak Republic. 28. Department of Cardiology I, Aristotle University of Thessaloniki, Thessaloniki, Greece. 29. German Rheumatism Research Center Berlin, Leibniz Institute, Berlin, Germany. 30. Bayer AG, Global Development, Global Medical Affairs, Berlin, Germany. 31. Department of Respiratory Medicine and the German Center for Lung Research, Hannover Medical School, Hannover, Germany.
Abstract
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 (CTEPH) 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 and collated via case report forms. RESULTS: In total, 956 patients with CTEPH were included in the analysis. The most common AEs in these patients were peripheral edema/edema (11.7%), dizziness (7.5%), right ventricular (RV)/cardiac failure (7.7%), and pneumonia (5.0%). The most common SAEs were RV/cardiac failure (7.4%), pneumonia (4.1%), dyspnea (3.6%), and syncope (2.5%). Exposure-adjusted rates of hemoptysis/pulmonary hemorrhage and hypotension were low and comparable to those in the long-term extension study of riociguat (Chronic Thromboembolic Pulmonary Hypertension Soluble Guanylate Cyclase-Stimulator Trial [CHEST-2]). CONCLUSION: Data from EXPERT show that in patients with CTEPH, the safety of riociguat in routine practice was consistent with the known safety profile of the drug, and no new safety concerns were identified.
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 (CTEPH) 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 and collated via case report forms. RESULTS: In total, 956 patients with CTEPH were included in the analysis. The most common AEs in these patients were peripheral edema/edema (11.7%), dizziness (7.5%), right ventricular (RV)/cardiac failure (7.7%), and pneumonia (5.0%). The most common SAEs were RV/cardiac failure (7.4%), pneumonia (4.1%), dyspnea (3.6%), and syncope (2.5%). Exposure-adjusted rates of hemoptysis/pulmonary hemorrhage and hypotension were low and comparable to those in the long-term extension study of riociguat (Chronic Thromboembolic Pulmonary Hypertension Soluble Guanylate Cyclase-Stimulator Trial [CHEST-2]). CONCLUSION: Data from EXPERT show that in patients with CTEPH, the safety of riociguat in routine practice was consistent with the known safety profile of the drug, and no new safety concerns were identified.