Michael Halank1, Marius M Hoeper2, Hossein-Ardeschir Ghofrani3, F Joachim Meyer4, Gerd Stähler5, Jürgen Behr6, Ralf Ewert7, Monique Fletcher8, Pablo Colorado9, Sylvia Nikkho10, Friedrich Grimminger11. 1. Medical Clinic 1/Pneumology, University Hospital Carl Gustav Carus, Dresden, Germany. Electronic address: Michael.Halank@uniklinikum-dresden.de. 2. Clinic for Respiratory Medicine, Hannover Medical School, Hannover, Germany, Member of the German Center of Lung Research (DZL). Electronic address: Hoeper.Marius@mh-hannover.de. 3. University of Giessen and Marburg Lung Center (UGMLC), Giessen, Germany, Member of the German Center of Lung Research (DZL); Department of Medicine, Imperial College London, London, UK. Electronic address: Ardeschir.Ghofrani@innere.med.uni-giessen.de. 4. Department of Cardiology and Respiratory Medicine, University Hospital, Heidelberg, Germany. Electronic address: Joachim.Meyer@urz.uni-heidelberg.de. 5. Medical Clinic 1, Loewenstein Clinic gGmbH, Loewenstein, Germany. Electronic address: gerd.staehler@klinik-loewenstein.de. 6. Department of Internal Medicine V, University of Munich and Asklepios Fachkliniken Munich-Gauting, Munich, Germany, Member of the German Center of Lung Research (DZL). Electronic address: Juergen.Behr@med.uni-muenchen.de. 7. Clinic for Internal Medicine B, Ernst-Moritz-Arndt-University Greifswald, Greifswald, Germany. Electronic address: docewert@t-online.de. 8. Global Clinical Development, Bayer plc, Newbury, UK. Electronic address: Monique.fletcher@bayer.com. 9. Global Clinical Development, Bayer Pharma AG, Parsippany, NJ, USA. Electronic address: pablo.colorado@bayer.com. 10. Global Clinical Development, Bayer Pharma AG, Berlin, Germany. Electronic address: sylvia.nikkho@bayer.com. 11. University of Giessen and Marburg Lung Center (UGMLC), Giessen, Germany, Member of the German Center of Lung Research (DZL). Electronic address: Friedrich.Grimminger@innere.med.uni-giessen.de.
Abstract
BACKGROUND: Riociguat was well tolerated and improved exercise and functional capacity in patients with pulmonary arterial hypertension (PAH) and inoperable chronic thromboembolic pulmonary hypertension (CTEPH) in a 12-week Phase II trial. We present final data from the long-term extension phase of this study. METHODS: During this multicenter, open-label, uncontrolled long-term extension study, riociguat dose could be changed at the physician's discretion (range 0.5-2.5 mg three times daily). The primary outcome was long-term safety and tolerability of riociguat; secondary outcomes included 6-minute walking distance, World Health Organization functional class, survival, and clinical worsening-free survival. RESULTS: Sixty-eight patients (inoperable CTEPH, n = 41; PAH, n = 27) entered the long-term extension. Median treatment duration at the final data cut-off was 77 months. The most common adverse events were nasopharyngitis (57%) and peripheral edema (37%). Three patients (4%) experienced serious adverse events of hemoptysis: two moderate, one severe, none fatal or considered drug-related. At Month 48, 6-minute walking distance increased from baseline by 69 ± 105 m, and World Health Organization functional class improved/stabilized/worsened versus baseline in 50/45/5% of patients. Three-year survival and clinical worsening-free survival were 91% and 49%, respectively (with patients censored if they withdrew without experiencing an event). Starting a new PAH treatment was the most frequent clinical worsening event. CONCLUSIONS: Improvements in exercise and functional capacity were maintained at 4 years in patients remaining on treatment, with no new safety signals identified. These data support riociguat as a long-term treatment option for PAH and inoperable CTEPH. TRIAL REGISTERED AT: ClinicalTrials.gov. REGISTRATION NUMBER: NCT00454558.
BACKGROUND:Riociguat was well tolerated and improved exercise and functional capacity in patients with pulmonary arterial hypertension (PAH) and inoperable chronic thromboembolic pulmonary hypertension (CTEPH) in a 12-week Phase II trial. We present final data from the long-term extension phase of this study. METHODS: During this multicenter, open-label, uncontrolled long-term extension study, riociguat dose could be changed at the physician's discretion (range 0.5-2.5 mg three times daily). The primary outcome was long-term safety and tolerability of riociguat; secondary outcomes included 6-minute walking distance, World Health Organization functional class, survival, and clinical worsening-free survival. RESULTS: Sixty-eight patients (inoperable CTEPH, n = 41; PAH, n = 27) entered the long-term extension. Median treatment duration at the final data cut-off was 77 months. The most common adverse events were nasopharyngitis (57%) and peripheral edema (37%). Three patients (4%) experienced serious adverse events of hemoptysis: two moderate, one severe, none fatal or considered drug-related. At Month 48, 6-minute walking distance increased from baseline by 69 ± 105 m, and World Health Organization functional class improved/stabilized/worsened versus baseline in 50/45/5% of patients. Three-year survival and clinical worsening-free survival were 91% and 49%, respectively (with patients censored if they withdrew without experiencing an event). Starting a new PAH treatment was the most frequent clinical worsening event. CONCLUSIONS: Improvements in exercise and functional capacity were maintained at 4 years in patients remaining on treatment, with no new safety signals identified. These data support riociguat as a long-term treatment option for PAH and inoperable CTEPH. TRIAL REGISTERED AT: ClinicalTrials.gov. REGISTRATION NUMBER: NCT00454558.
Authors: Stefan Guth; Andrea M D'Armini; Marion Delcroix; Kazuhiko Nakayama; Elie Fadel; Stephen P Hoole; David P Jenkins; David G Kiely; Nick H Kim; Irene M Lang; Michael M Madani; Hiromi Matsubara; Aiko Ogawa; Jaquelina S Ota-Arakaki; Rozenn Quarck; Roela Sadushi-Kolici; Gérald Simonneau; Christoph B Wiedenroth; Bedrettin Yildizeli; Eckhard Mayer; Joanna Pepke-Zaba Journal: ERJ Open Res Date: 2021-08-16