Riociguat treatment in patients with chronic thromboembolic pulmonary hypertension: Final safety data from the EXPERT registry

Hossein Ardeschir Ghofrani; Miguel Angel Gomez Sanchez; Marc Humbert; David Pittrow; Gérald Simonneau; Henning Gall; Ekkehard Grünig; Hans Klose; Michael Halank; David Langleben; Repke J. Snijder; Pilar Escribano Subias; Lisa M. Mielniczuk; Tobias J. Lange; Jean Luc Vachiéry; Hubert Wirtz; Douglas S. Helmersen; Iraklis Tsangaris; Joan A. Barberá; Joanna Pepke-Zaba; Anco Boonstra; Stephan Rosenkranz; Silvia Ulrich; Regina Steringer-Mascherbauer; Marion Delcroix; Pavel Jansa; Iveta Šimková; George Giannakoulas; Jens Klotsche; Evgenia Williams; Christian Meier; Marius M. Hoeper; Jorge Caneva; Graciela Tuhay; Mirta Diez; Maria Lujan Talavera; Adriana Acosta; Norberto Vulcano; Martin Bosio; Lorena Maldonado; Sabino Deleo; Luciano Melatini; Anne Keogh; Eugene Kotlyar; John Feenstra; Nathan Dwyer; Heath Adams; Wendy Stevens; Peter Steele; Myriam Alexandre; NEW COLLABORATORS LIST

doi:10.1016/j.rmed.2020.106220

Riociguat treatment in patients with chronic thromboembolic pulmonary hypertension: Final safety data from the EXPERT registry

Hossein Ardeschir Ghofrani^*, Miguel Angel Gomez Sanchez, Marc Humbert, David Pittrow, Gérald Simonneau, Henning Gall, Ekkehard Grünig, Hans Klose, Michael Halank, David Langleben, Repke J. Snijder, Pilar Escribano Subias, Lisa M. Mielniczuk, Tobias J. Lange, Jean Luc Vachiéry, Hubert Wirtz, Douglas S. Helmersen, Iraklis Tsangaris, Joan A. Barberá, Joanna Pepke-ZabaAnco Boonstra, Stephan Rosenkranz, Silvia Ulrich, Regina Steringer-Mascherbauer, Marion Delcroix, Pavel Jansa, Iveta Šimková, George Giannakoulas, Jens Klotsche, Evgenia Williams, Christian Meier, Marius M. Hoeper, Jorge Caneva, Graciela Tuhay, Mirta Diez, Maria Lujan Talavera, Adriana Acosta, Norberto Vulcano, Martin Bosio, Lorena Maldonado, Sabino Deleo, Luciano Melatini, Anne Keogh, Eugene Kotlyar, John Feenstra, Nathan Dwyer, Heath Adams, Wendy Stevens, Peter Steele, Myriam Alexandre, NEW COLLABORATORS LIST

^*Corresponding author for this work

Research output: Contribution to journal › Article › Research › peer-review

21 Citations (Scopus)

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.

Original language	English
Article number	106220
Journal	Respiratory Medicine
Volume	178
DOIs	https://doi.org/10.1016/j.rmed.2020.106220
Publication status	Published - Mar 2021
Externally published	Yes

Keywords

Chronic thromboembolic pulmonary hypertension
Clinical practice
Real-world
Registry
Riociguat
Safety

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10.1016/j.rmed.2020.106220

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Ghofrani, H. A., Gomez Sanchez, M. A., Humbert, M., Pittrow, D., Simonneau, G., Gall, H., Grünig, E., Klose, H., Halank, M., Langleben, D., Snijder, R. J., Escribano Subias, P., Mielniczuk, L. M., Lange, T. J., Vachiéry, J. L., Wirtz, H., Helmersen, D. S., Tsangaris, I., Barberá, J. A., ... NEW COLLABORATORS LIST (2021). Riociguat treatment in patients with chronic thromboembolic pulmonary hypertension: Final safety data from the EXPERT registry. Respiratory Medicine, 178, Article 106220. https://doi.org/10.1016/j.rmed.2020.106220

@article{986b94cd438c40eb8ba72dcd39237f58,

title = "Riociguat treatment in patients with chronic thromboembolic pulmonary hypertension: Final safety data from the EXPERT registry",

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.",

keywords = "Chronic thromboembolic pulmonary hypertension, Clinical practice, Real-world, Registry, Riociguat, Safety",

author = "Ghofrani, {Hossein Ardeschir} and {Gomez Sanchez}, {Miguel Angel} and Marc Humbert and David Pittrow and G{\'e}rald Simonneau and Henning Gall and Ekkehard Gr{\"u}nig and Hans Klose and Michael Halank and David Langleben and Snijder, {Repke J.} and {Escribano Subias}, Pilar and Mielniczuk, {Lisa M.} and Lange, {Tobias J.} and Vachi{\'e}ry, {Jean Luc} and Hubert Wirtz and Helmersen, {Douglas S.} and Iraklis Tsangaris and Barber{\'a}, {Joan A.} and Joanna Pepke-Zaba and Anco Boonstra and Stephan Rosenkranz and Silvia Ulrich and Regina Steringer-Mascherbauer and Marion Delcroix and Pavel Jansa and Iveta {\v S}imkov{\'a} and George Giannakoulas and Jens Klotsche and Evgenia Williams and Christian Meier and Hoeper, {Marius M.} and Jorge Caneva and Graciela Tuhay and Mirta Diez and Talavera, {Maria Lujan} and Adriana Acosta and Norberto Vulcano and Martin Bosio and Lorena Maldonado and Sabino Deleo and Luciano Melatini and Anne Keogh and Eugene Kotlyar and John Feenstra and Nathan Dwyer and Heath Adams and Wendy Stevens and Peter Steele and Myriam Alexandre and {NEW COLLABORATORS LIST}",

note = "Funding Information: The EXPERT registry was funded by Bayer AG (Berlin, Germany) and Merck Sharp & Dohme Corp., a subsidiary of Merck & Co. Inc., Kenilworth, NJ, USA. The authors acknowledge the database administration by Torsten Tille, Dresden, and the project administration of Mrs Romy Hoppenz and Mrs Linda Kottke at GWT-TUD GmbH, Dresden. Medical writing services provided by Richard Murphy PhD of Adelphi Communications Ltd, Macclesfield, UK were funded by Bayer AG in accordance with Good Publication Practice (GPP3) guidelines. Funding Information: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Prof Marius M. Hoeper reports personal fees from Bayer AG, during the conduct of the study; personal fees from Actelion, personal fees from Acceleron, personal fees from MSD, personal fees from Jansen, personal fees from Pfizer, outside the submitted work. Dr Hans Klose reports speaker and consultancy fees from Actelion, Bayer AG, GSK, Novartis, Pfizer, and United Therapeutics and research support from Actelion, Bayer AG, GSK, Pfizer, and MSD. Dr Michael Halank reports personal fees and non-financial support from Actelion, AstraZeneca, Bayer AG, Berlin-Chemie, GSK, OMT, MSD, and Novartis. Dr George Giannakoulas reports speaker and consultancy fees from Actelion, Bayer, ELPEN Pharmaceuticals, GSK, Pfizer, Lilly, and United Therapeutics, and research support from GSK, ELPEN Pharmaceuticals, and Galenica. Dr Henning Gall has received honoraria and/or other support from Actelion, AstraZeneca, Bayer, BMS, GSK, Janssen-Cilag, Lilly, MSD, Novartis, OMT, Pfizer, and United Therapeutics. Dr Pavel Jansa reports consultancy and speaker fees from MSD, AOP Orphan, and Actelion. Prof Ekkehard Gr{\"u}nig reports research grants and speaker honoraria/consultancy fees from Actelion and Bayer/MSD, research grants from GSK, United Therapeutics, Bellerophon, OMT GmbH, Pfizer, Reata, and Novartis, and speaker honoraria from Bial, Medscape, and OrPha Swiss GmbH. Prof David Pittrow reports personal fees from Actelion, Bayer AG, Aspen, Boehringer Ingelheim, Sanofi, Biogen, Shire, and MSD outside the submitted work. Silvia Ulrich reports research grants and personal fees from Actelion, Bayer, MSD, and Orpha Swiss. Tobias J. Lange has received personal fees from Actelion, MSD, Pfizer, and OMT orphan. Dr Iraklis Tsangaris reports speaker and consultancy fees from Actelion, Bayer AG, ELPEN, GSK, MSD, Pfizer, and United Therapeutics. Stephan Rosenkranz reports remunerations for lectures and/or consultancy from Abbott, Actelion, Arena, Bayer, Ferrer, GSK, MSD, Novartis, Pfizer, and United Therapeutics; and research support to his institution from Actelion, Bayer, Novartis, Pfizer, and United Therapeutics. Repke J. Snijder reports grants from Pfizer and Actelion Pharmaceuticals. Prof Iveta {\v S}imkov{\'a} reports consultancy and speaker fees from MSD, AOP Orphan, and Actelion. Dr Marc Humbert reports grants and personal fees from Bayer and GSK, and personal fees from Actelion, Merck, and United Therapeutics. Marion Delcroix has received investigator, speaker, consultant, and steering committee member fees from Actelion, Bayer AG, Bellerophon, Eli Lilly, GlaxoSmithKline, MSD, Pfizer, and Reata, and research grants from Actelion. Joan A. Barber{\`a} reports receipt of honoraria for consultation or speaker fees from Actelion and Merck; and research support through his institution from Actelion, Merck, GlaxoSmithKline, and Ferrer. Joanna Pepke-Zaba reports research grants and speaker honoraria/consultancy fees from Actelion, Bayer/MSD, and GSK. Jean-Luc Vachi{\'e}ry reports ongoing consultancies to Actelion, Sonnivie, Arena Pharma, Bial Portela, and Respira Therapeutics, past consultancies to AstraZeneca, BayerShering, CardioMEMS, GlaxoSmithKline, Pfizer, Merck, and United Therapeutics, and current membership of an advisory board or similar group for Actelion and GlaxoSmithKline. Jean-Luc Vachi{\'e}ry's institution receives funding from Actelion Pharmaceuticals for performing clinical studies. Regina Steringer-Mascherbauer, Jens Klotsche, and Miguel-Angel Gomez Sanchez have no conflicts of interest relevant to the EXPERT study. Hossein-Ardeschir Ghofrani reports personal fees for advisory board work, and payment for lectures including service on speaker bureaus, from Actelion, Bayer, GSK, Novartis, and Pfizer; consultancy fees from Actelion, Bayer, Bellerophon Pulse Technologies, GSK, MSD, Novartis, and Pfizer; and grants from Deutsche Forschungsgemeinschaft (DFG). Pilar Escribano Subias reports personal fees from Actelion, Bayer AG, GlaxoSmithKline, and Merck Sharp & Dohme, and grants from Actelion, Bayer AG, GlaxoSmithKline, and Ferrer, outside the submitted work. G{\'e}rald Simonneau reports personal fees and non-financial support from Actelion, personal fees and non-financial support from Bayer, personal fees and non-financial support from MSD, outside the submitted work. Douglas S. Helmersen reports industry-sponsored research with Bayer AG, United Therapeutics, and Gilead Sciences, Inc., and advisory board/speaker fees from Bayer AG and Actelion. David Langleben reports honoraria, consultation fees, research support, and/or travel expenses from Actelion, Arena, Bayer AG, Northern Therapeutics, PhaseBio, Acceleron, Janssen, and United Therapeutics. Anco Boonstra reports consultancy fees from Pfizer BV and hospitality from Teva Nederland. Lisa M. Mielniczuk reports speaker fees and honoraria from Bayer AG, and speaker fees, consultancy fees, and travel fees from Actelion. Evgenia Williams and Christian Meier are employees of Bayer AG. Publisher Copyright: {\textcopyright} 2020 The Authors",

year = "2021",

month = mar,

doi = "10.1016/j.rmed.2020.106220",

language = "English",

volume = "178",

journal = "Respiratory Medicine",

issn = "0954-6111",

publisher = "W.B. Saunders Ltd",

}

Ghofrani, HA, Gomez Sanchez, MA, Humbert, M, Pittrow, D, Simonneau, G, Gall, H, Grünig, E, Klose, H, Halank, M, Langleben, D, Snijder, RJ, Escribano Subias, P, Mielniczuk, LM, Lange, TJ, Vachiéry, JL, Wirtz, H, Helmersen, DS, Tsangaris, I, Barberá, JA, Pepke-Zaba, J, Boonstra, A, Rosenkranz, S, Ulrich, S, Steringer-Mascherbauer, R, Delcroix, M, Jansa, P, Šimková, I, Giannakoulas, G, Klotsche, J, Williams, E, Meier, C, Hoeper, MM, Caneva, J, Tuhay, G, Diez, M, Talavera, ML, Acosta, A, Vulcano, N, Bosio, M, Maldonado, L, Deleo, S, Melatini, L, Keogh, A, Kotlyar, E, Feenstra, J, Dwyer, N, Adams, H, Stevens, W, Steele, P, Alexandre, M & NEW COLLABORATORS LIST 2021, 'Riociguat treatment in patients with chronic thromboembolic pulmonary hypertension: Final safety data from the EXPERT registry', Respiratory Medicine, vol. 178, 106220. https://doi.org/10.1016/j.rmed.2020.106220

TY - JOUR

T1 - Riociguat treatment in patients with chronic thromboembolic pulmonary hypertension

T2 - Final safety data from the EXPERT registry

AU - Ghofrani, Hossein Ardeschir

AU - Gomez Sanchez, Miguel Angel

AU - Humbert, Marc

AU - Pittrow, David

AU - Simonneau, Gérald

AU - Gall, Henning

AU - Grünig, Ekkehard

AU - Klose, Hans

AU - Halank, Michael

AU - Langleben, David

AU - Snijder, Repke J.

AU - Escribano Subias, Pilar

AU - Mielniczuk, Lisa M.

AU - Lange, Tobias J.

AU - Vachiéry, Jean Luc

AU - Wirtz, Hubert

AU - Helmersen, Douglas S.

AU - Tsangaris, Iraklis

AU - Barberá, Joan A.

AU - Pepke-Zaba, Joanna

AU - Boonstra, Anco

AU - Rosenkranz, Stephan

AU - Ulrich, Silvia

AU - Steringer-Mascherbauer, Regina

AU - Delcroix, Marion

AU - Jansa, Pavel

AU - Šimková, Iveta

AU - Giannakoulas, George

AU - Klotsche, Jens

AU - Williams, Evgenia

AU - Meier, Christian

AU - Hoeper, Marius M.

AU - Caneva, Jorge

AU - Tuhay, Graciela

AU - Diez, Mirta

AU - Talavera, Maria Lujan

AU - Acosta, Adriana

AU - Vulcano, Norberto

AU - Bosio, Martin

AU - Maldonado, Lorena

AU - Deleo, Sabino

AU - Melatini, Luciano

AU - Keogh, Anne

AU - Kotlyar, Eugene

AU - Feenstra, John

AU - Dwyer, Nathan

AU - Adams, Heath

AU - Stevens, Wendy

AU - Steele, Peter

AU - Alexandre, Myriam

AU - NEW COLLABORATORS LIST

N1 - Funding Information: The EXPERT registry was funded by Bayer AG (Berlin, Germany) and Merck Sharp & Dohme Corp., a subsidiary of Merck & Co. Inc., Kenilworth, NJ, USA. The authors acknowledge the database administration by Torsten Tille, Dresden, and the project administration of Mrs Romy Hoppenz and Mrs Linda Kottke at GWT-TUD GmbH, Dresden. Medical writing services provided by Richard Murphy PhD of Adelphi Communications Ltd, Macclesfield, UK were funded by Bayer AG in accordance with Good Publication Practice (GPP3) guidelines. Funding Information: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Prof Marius M. Hoeper reports personal fees from Bayer AG, during the conduct of the study; personal fees from Actelion, personal fees from Acceleron, personal fees from MSD, personal fees from Jansen, personal fees from Pfizer, outside the submitted work. Dr Hans Klose reports speaker and consultancy fees from Actelion, Bayer AG, GSK, Novartis, Pfizer, and United Therapeutics and research support from Actelion, Bayer AG, GSK, Pfizer, and MSD. Dr Michael Halank reports personal fees and non-financial support from Actelion, AstraZeneca, Bayer AG, Berlin-Chemie, GSK, OMT, MSD, and Novartis. Dr George Giannakoulas reports speaker and consultancy fees from Actelion, Bayer, ELPEN Pharmaceuticals, GSK, Pfizer, Lilly, and United Therapeutics, and research support from GSK, ELPEN Pharmaceuticals, and Galenica. Dr Henning Gall has received honoraria and/or other support from Actelion, AstraZeneca, Bayer, BMS, GSK, Janssen-Cilag, Lilly, MSD, Novartis, OMT, Pfizer, and United Therapeutics. Dr Pavel Jansa reports consultancy and speaker fees from MSD, AOP Orphan, and Actelion. Prof Ekkehard Grünig reports research grants and speaker honoraria/consultancy fees from Actelion and Bayer/MSD, research grants from GSK, United Therapeutics, Bellerophon, OMT GmbH, Pfizer, Reata, and Novartis, and speaker honoraria from Bial, Medscape, and OrPha Swiss GmbH. Prof David Pittrow reports personal fees from Actelion, Bayer AG, Aspen, Boehringer Ingelheim, Sanofi, Biogen, Shire, and MSD outside the submitted work. Silvia Ulrich reports research grants and personal fees from Actelion, Bayer, MSD, and Orpha Swiss. Tobias J. Lange has received personal fees from Actelion, MSD, Pfizer, and OMT orphan. Dr Iraklis Tsangaris reports speaker and consultancy fees from Actelion, Bayer AG, ELPEN, GSK, MSD, Pfizer, and United Therapeutics. Stephan Rosenkranz reports remunerations for lectures and/or consultancy from Abbott, Actelion, Arena, Bayer, Ferrer, GSK, MSD, Novartis, Pfizer, and United Therapeutics; and research support to his institution from Actelion, Bayer, Novartis, Pfizer, and United Therapeutics. Repke J. Snijder reports grants from Pfizer and Actelion Pharmaceuticals. Prof Iveta Šimková reports consultancy and speaker fees from MSD, AOP Orphan, and Actelion. Dr Marc Humbert reports grants and personal fees from Bayer and GSK, and personal fees from Actelion, Merck, and United Therapeutics. Marion Delcroix has received investigator, speaker, consultant, and steering committee member fees from Actelion, Bayer AG, Bellerophon, Eli Lilly, GlaxoSmithKline, MSD, Pfizer, and Reata, and research grants from Actelion. Joan A. Barberà reports receipt of honoraria for consultation or speaker fees from Actelion and Merck; and research support through his institution from Actelion, Merck, GlaxoSmithKline, and Ferrer. Joanna Pepke-Zaba reports research grants and speaker honoraria/consultancy fees from Actelion, Bayer/MSD, and GSK. Jean-Luc Vachiéry reports ongoing consultancies to Actelion, Sonnivie, Arena Pharma, Bial Portela, and Respira Therapeutics, past consultancies to AstraZeneca, BayerShering, CardioMEMS, GlaxoSmithKline, Pfizer, Merck, and United Therapeutics, and current membership of an advisory board or similar group for Actelion and GlaxoSmithKline. Jean-Luc Vachiéry's institution receives funding from Actelion Pharmaceuticals for performing clinical studies. Regina Steringer-Mascherbauer, Jens Klotsche, and Miguel-Angel Gomez Sanchez have no conflicts of interest relevant to the EXPERT study. Hossein-Ardeschir Ghofrani reports personal fees for advisory board work, and payment for lectures including service on speaker bureaus, from Actelion, Bayer, GSK, Novartis, and Pfizer; consultancy fees from Actelion, Bayer, Bellerophon Pulse Technologies, GSK, MSD, Novartis, and Pfizer; and grants from Deutsche Forschungsgemeinschaft (DFG). Pilar Escribano Subias reports personal fees from Actelion, Bayer AG, GlaxoSmithKline, and Merck Sharp & Dohme, and grants from Actelion, Bayer AG, GlaxoSmithKline, and Ferrer, outside the submitted work. Gérald Simonneau reports personal fees and non-financial support from Actelion, personal fees and non-financial support from Bayer, personal fees and non-financial support from MSD, outside the submitted work. Douglas S. Helmersen reports industry-sponsored research with Bayer AG, United Therapeutics, and Gilead Sciences, Inc., and advisory board/speaker fees from Bayer AG and Actelion. David Langleben reports honoraria, consultation fees, research support, and/or travel expenses from Actelion, Arena, Bayer AG, Northern Therapeutics, PhaseBio, Acceleron, Janssen, and United Therapeutics. Anco Boonstra reports consultancy fees from Pfizer BV and hospitality from Teva Nederland. Lisa M. Mielniczuk reports speaker fees and honoraria from Bayer AG, and speaker fees, consultancy fees, and travel fees from Actelion. Evgenia Williams and Christian Meier are employees of Bayer AG. Publisher Copyright: © 2020 The Authors

PY - 2021/3

Y1 - 2021/3

N2 - 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.

AB - 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.

KW - Chronic thromboembolic pulmonary hypertension

KW - Clinical practice

KW - Real-world

KW - Registry

KW - Riociguat

KW - Safety

UR - http://www.scopus.com/inward/record.url?scp=85100409820&partnerID=8YFLogxK

UR - https://pubmed.ncbi.nlm.nih.gov/33540340

U2 - 10.1016/j.rmed.2020.106220

DO - 10.1016/j.rmed.2020.106220

M3 - Article

C2 - 33540340

AN - SCOPUS:85100409820

SN - 0954-6111

VL - 178

JO - Respiratory Medicine

JF - Respiratory Medicine

M1 - 106220

ER -

Riociguat treatment in patients with chronic thromboembolic pulmonary hypertension: Final safety data from the EXPERT registry

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Keywords

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