Identifying potential parameters associated with response to switching from a PDE5i to riociguat in RESPITE

Raymond L. Benza; Paul A. Corris; James R. Klinger; David Langleben; Robert Naeije; Gérald Simonneau; Hossein Ardeschir Ghofrani; Pavel Jansa; Stephan Rosenkranz; Laura Scelsi; Thenappan Thenappan; Amresh Raina; Christian Meier; Dennis Busse; Marius M. Hoeper

doi:10.1016/j.ijcard.2020.05.044

Identifying potential parameters associated with response to switching from a PDE5i to riociguat in RESPITE

Raymond L. Benza, Paul A. Corris, James R. Klinger, David Langleben, Robert Naeije, Gérald Simonneau, Hossein Ardeschir Ghofrani, Pavel Jansa, Stephan Rosenkranz, Laura Scelsi, Thenappan Thenappan, Amresh Raina, Christian Meier, Dennis Busse, Marius M. Hoeper

Medicine - Cardiology Division

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

4 Scopus citations

Abstract

Background: RESPITE evaluated patients with pulmonary arterial hypertension and an inadequate response to phosphodiesterase type 5 inhibitors (PDE5i) who switched to riociguat. This post hoc analysis assessed response to this switch in parameters associated with clinical improvement. Methods: RESPITE was a 24-week, uncontrolled pilot study (n = 61). Differences in functional, hemodynamic, and cardiac function parameters, REVEAL risk score (RRS), and biomarkers were compared between responders (free from clinical worsening, World Health Organization functional class I/II, and ≥30 m improvement in 6-min walking distance at Week 24) and non-responders. Results: Of 51 patients (84%) completing RESPITE, 16 (31%) met the responder endpoint. At baseline, there were significant differences between responders and non-responders in N-terminal prohormone of brain natriuretic peptide (NT-proBNP), growth/differentiation factor 15 (GDF-15), and RRS, whereas there were no differences in hemodynamics or cardiac function. At Week 24, responders had significant improvements in pulmonary arterial compliance, pulmonary vascular resistance, and mean pulmonary arterial pressure, while non-responders showed no significant change. Cardiac efficiency and stroke volume index significantly improved irrespective of responder status. Conclusions: NT-proBNP, GDF-15, and RRS were identified as potential predictors of response in patients switching from PDE5i to riociguat. Further prospective controlled studies are needed to confirm the association of these parameters with response.

Original language	English (US)
Pages (from-to)	188-192
Number of pages	5
Journal	International Journal of Cardiology
Volume	317
DOIs	https://doi.org/10.1016/j.ijcard.2020.05.044
State	Published - Oct 15 2020

Bibliographical note

Funding Information:
The RESPITE study was funded by Bayer AG, Berlin, Germany and Merck & Co., Inc., Kenilworth, NJ USA. Medical writing services provided by Robyn Bradbury PhD, of Adelphi Communications Ltd., Macclesfield, UK were funded by Bayer AG, in accordance with Good Publications Practice 3 guidelines.

Funding Information:
RLB reports grants from Bellerophon , Bayer AG , Actelion , and EIGER . PAC reports grants and personal fees (University Research Fund) from Bayer AG , and personal fees from Actelion and GSK . JRK reports his institution received grant support for clinical trials in pulmonary hypertension from Actelion , Bayer AG , Lung Biotechnology , and United Therapeutics . DL reports honoraria, consultation fees, research support, and/or travel expenses from Actelion, Arena, Bayer AG, Northern Therapeutic, PhaseBio, and United Therapeutics. RN reports Advisory Board member fees from Actelion, Bayer AG, and Lung Biotechnology Corporation, personal fees from Actelion and GSK, and grants from Reata . GS reports grants, personal fees, and non-financial support from Actelion , Bayer AG , GSK , and Merck . HAG reports grants and personal fees from Actelion , Bayer AG , Ergonex , and Pfizer , and personal fees from Gilead, GSK, Merck, and Novartis. PJ reports being an investigator for Actelion and Bayer AG, and personal fees from AOP. SR reports grants and personal fees from Actelion , Bayer AG , Gilead , GSK , Novartis , Pfizer , United Therapeutics , Arena , Ferrer , Merck Sharp & Dohme , and Abbott , and research support from Actelion , Bayer AG , Novartis , Pfizer , and United Therapeutics . LS has nothing to disclose. TT reports personal fees (Advisory Board/CME) from Actelion and Gilead. AR reports honoraria from Bayer AG, research support from United Therapeutics , and consulting fees from St Jude. CM is an employee of Bayer AG. DB was an employee of Chrestos Concept GmBH & Co during writing of the manuscript. MMH reports consultancy fees from Actelion, Bayer AG, and Pfizer, and personal fees from Actelion, Bayer AG, Pfizer, and MSD.

Funding Information:
RLB reports grants from Bellerophon, Bayer AG, Actelion, and EIGER. PAC reports grants and personal fees (University Research Fund) from Bayer AG, and personal fees from Actelion and GSK. JRK reports his institution received grant support for clinical trials in pulmonary hypertension from Actelion, Bayer AG, Lung Biotechnology, and United Therapeutics. DL reports honoraria, consultation fees, research support, and/or travel expenses from Actelion, Arena, Bayer AG, Northern Therapeutic, PhaseBio, and United Therapeutics. RN reports Advisory Board member fees from Actelion, Bayer AG, and Lung Biotechnology Corporation, personal fees from Actelion and GSK, and grants from Reata. GS reports grants, personal fees, and non-financial support from Actelion, Bayer AG, GSK, and Merck. HAG reports grants and personal fees from Actelion, Bayer AG, Ergonex, and Pfizer, and personal fees from Gilead, GSK, Merck, and Novartis. PJ reports being an investigator for Actelion and Bayer AG, and personal fees from AOP. SR reports grants and personal fees from Actelion, Bayer AG, Gilead, GSK, Novartis, Pfizer, United Therapeutics, Arena, Ferrer, Merck Sharp& Dohme, and Abbott, and research support from Actelion, Bayer AG, Novartis, Pfizer, and United Therapeutics. LS has nothing to disclose. TT reports personal fees (Advisory Board/CME) from Actelion and Gilead. AR reports honoraria from Bayer AG, research support from United Therapeutics, and consulting fees from St Jude. CM is an employee of Bayer AG. DB was an employee of Chrestos Concept GmBH & Co during writing of the manuscript. MMH reports consultancy fees from Actelion, Bayer AG, and Pfizer, and personal fees from Actelion, Bayer AG, Pfizer, and MSD.The RESPITE study was funded by Bayer AG, Berlin, Germany and Merck & Co. Inc. Kenilworth, NJ USA. Medical writing services provided by Robyn Bradbury PhD, of Adelphi Communications Ltd. Macclesfield, UK were funded by Bayer AG, in accordance with Good Publications Practice 3 guidelines.

Publisher Copyright:
© 2020 The Authors

Keywords

Biomarkers
Pulmonary arterial hypertension
Pulmonary hemodynamics
Right heart function
Riociguat
Switching to riociguat

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10.1016/j.ijcard.2020.05.044

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Benza, R. L., Corris, P. A., Klinger, J. R., Langleben, D., Naeije, R., Simonneau, G., Ghofrani, H. A., Jansa, P., Rosenkranz, S., Scelsi, L., Thenappan, T., Raina, A., Meier, C., Busse, D., & Hoeper, M. M. (2020). Identifying potential parameters associated with response to switching from a PDE5i to riociguat in RESPITE. International Journal of Cardiology, 317, 188-192. https://doi.org/10.1016/j.ijcard.2020.05.044

Benza, RL, Corris, PA, Klinger, JR, Langleben, D, Naeije, R, Simonneau, G, Ghofrani, HA, Jansa, P, Rosenkranz, S, Scelsi, L, Thenappan, T, Raina, A, Meier, C, Busse, D & Hoeper, MM 2020, 'Identifying potential parameters associated with response to switching from a PDE5i to riociguat in RESPITE', International Journal of Cardiology, vol. 317, pp. 188-192. https://doi.org/10.1016/j.ijcard.2020.05.044

@article{e8f36f55dbea46f889e2d5c834dbc481,

title = "Identifying potential parameters associated with response to switching from a PDE5i to riociguat in RESPITE",

abstract = "Background: RESPITE evaluated patients with pulmonary arterial hypertension and an inadequate response to phosphodiesterase type 5 inhibitors (PDE5i) who switched to riociguat. This post hoc analysis assessed response to this switch in parameters associated with clinical improvement. Methods: RESPITE was a 24-week, uncontrolled pilot study (n = 61). Differences in functional, hemodynamic, and cardiac function parameters, REVEAL risk score (RRS), and biomarkers were compared between responders (free from clinical worsening, World Health Organization functional class I/II, and ≥30 m improvement in 6-min walking distance at Week 24) and non-responders. Results: Of 51 patients (84%) completing RESPITE, 16 (31%) met the responder endpoint. At baseline, there were significant differences between responders and non-responders in N-terminal prohormone of brain natriuretic peptide (NT-proBNP), growth/differentiation factor 15 (GDF-15), and RRS, whereas there were no differences in hemodynamics or cardiac function. At Week 24, responders had significant improvements in pulmonary arterial compliance, pulmonary vascular resistance, and mean pulmonary arterial pressure, while non-responders showed no significant change. Cardiac efficiency and stroke volume index significantly improved irrespective of responder status. Conclusions: NT-proBNP, GDF-15, and RRS were identified as potential predictors of response in patients switching from PDE5i to riociguat. Further prospective controlled studies are needed to confirm the association of these parameters with response.",

keywords = "Biomarkers, Pulmonary arterial hypertension, Pulmonary hemodynamics, Right heart function, Riociguat, Switching to riociguat",

author = "Benza, {Raymond L.} and Corris, {Paul A.} and Klinger, {James R.} and David Langleben and Robert Naeije and G{\'e}rald Simonneau and Ghofrani, {Hossein Ardeschir} and Pavel Jansa and Stephan Rosenkranz and Laura Scelsi and Thenappan Thenappan and Amresh Raina and Christian Meier and Dennis Busse and Hoeper, {Marius M.}",

note = "Funding Information: The RESPITE study was funded by Bayer AG, Berlin, Germany and Merck & Co., Inc., Kenilworth, NJ USA. Medical writing services provided by Robyn Bradbury PhD, of Adelphi Communications Ltd., Macclesfield, UK were funded by Bayer AG, in accordance with Good Publications Practice 3 guidelines. Funding Information: RLB reports grants from Bellerophon , Bayer AG , Actelion , and EIGER . PAC reports grants and personal fees (University Research Fund) from Bayer AG , and personal fees from Actelion and GSK . JRK reports his institution received grant support for clinical trials in pulmonary hypertension from Actelion , Bayer AG , Lung Biotechnology , and United Therapeutics . DL reports honoraria, consultation fees, research support, and/or travel expenses from Actelion, Arena, Bayer AG, Northern Therapeutic, PhaseBio, and United Therapeutics. RN reports Advisory Board member fees from Actelion, Bayer AG, and Lung Biotechnology Corporation, personal fees from Actelion and GSK, and grants from Reata . GS reports grants, personal fees, and non-financial support from Actelion , Bayer AG , GSK , and Merck . HAG reports grants and personal fees from Actelion , Bayer AG , Ergonex , and Pfizer , and personal fees from Gilead, GSK, Merck, and Novartis. PJ reports being an investigator for Actelion and Bayer AG, and personal fees from AOP. SR reports grants and personal fees from Actelion , Bayer AG , Gilead , GSK , Novartis , Pfizer , United Therapeutics , Arena , Ferrer , Merck Sharp & Dohme , and Abbott , and research support from Actelion , Bayer AG , Novartis , Pfizer , and United Therapeutics . LS has nothing to disclose. TT reports personal fees (Advisory Board/CME) from Actelion and Gilead. AR reports honoraria from Bayer AG, research support from United Therapeutics , and consulting fees from St Jude. CM is an employee of Bayer AG. DB was an employee of Chrestos Concept GmBH & Co during writing of the manuscript. MMH reports consultancy fees from Actelion, Bayer AG, and Pfizer, and personal fees from Actelion, Bayer AG, Pfizer, and MSD. Funding Information: RLB reports grants from Bellerophon, Bayer AG, Actelion, and EIGER. PAC reports grants and personal fees (University Research Fund) from Bayer AG, and personal fees from Actelion and GSK. JRK reports his institution received grant support for clinical trials in pulmonary hypertension from Actelion, Bayer AG, Lung Biotechnology, and United Therapeutics. DL reports honoraria, consultation fees, research support, and/or travel expenses from Actelion, Arena, Bayer AG, Northern Therapeutic, PhaseBio, and United Therapeutics. RN reports Advisory Board member fees from Actelion, Bayer AG, and Lung Biotechnology Corporation, personal fees from Actelion and GSK, and grants from Reata. GS reports grants, personal fees, and non-financial support from Actelion, Bayer AG, GSK, and Merck. HAG reports grants and personal fees from Actelion, Bayer AG, Ergonex, and Pfizer, and personal fees from Gilead, GSK, Merck, and Novartis. PJ reports being an investigator for Actelion and Bayer AG, and personal fees from AOP. SR reports grants and personal fees from Actelion, Bayer AG, Gilead, GSK, Novartis, Pfizer, United Therapeutics, Arena, Ferrer, Merck Sharp& Dohme, and Abbott, and research support from Actelion, Bayer AG, Novartis, Pfizer, and United Therapeutics. LS has nothing to disclose. TT reports personal fees (Advisory Board/CME) from Actelion and Gilead. AR reports honoraria from Bayer AG, research support from United Therapeutics, and consulting fees from St Jude. CM is an employee of Bayer AG. DB was an employee of Chrestos Concept GmBH & Co during writing of the manuscript. MMH reports consultancy fees from Actelion, Bayer AG, and Pfizer, and personal fees from Actelion, Bayer AG, Pfizer, and MSD.The RESPITE study was funded by Bayer AG, Berlin, Germany and Merck & Co. Inc. Kenilworth, NJ USA. Medical writing services provided by Robyn Bradbury PhD, of Adelphi Communications Ltd. Macclesfield, UK were funded by Bayer AG, in accordance with Good Publications Practice 3 guidelines. Publisher Copyright: {\textcopyright} 2020 The Authors",

year = "2020",

month = oct,

day = "15",

doi = "10.1016/j.ijcard.2020.05.044",

language = "English (US)",

volume = "317",

pages = "188--192",

journal = "International Journal of Cardiology",

issn = "0167-5273",

publisher = "Elsevier Ireland Ltd",

}

TY - JOUR

T1 - Identifying potential parameters associated with response to switching from a PDE5i to riociguat in RESPITE

AU - Benza, Raymond L.

AU - Corris, Paul A.

AU - Klinger, James R.

AU - Langleben, David

AU - Naeije, Robert

AU - Simonneau, Gérald

AU - Ghofrani, Hossein Ardeschir

AU - Jansa, Pavel

AU - Rosenkranz, Stephan

AU - Scelsi, Laura

AU - Thenappan, Thenappan

AU - Raina, Amresh

AU - Meier, Christian

AU - Busse, Dennis

AU - Hoeper, Marius M.

N1 - Funding Information: The RESPITE study was funded by Bayer AG, Berlin, Germany and Merck & Co., Inc., Kenilworth, NJ USA. Medical writing services provided by Robyn Bradbury PhD, of Adelphi Communications Ltd., Macclesfield, UK were funded by Bayer AG, in accordance with Good Publications Practice 3 guidelines. Funding Information: RLB reports grants from Bellerophon , Bayer AG , Actelion , and EIGER . PAC reports grants and personal fees (University Research Fund) from Bayer AG , and personal fees from Actelion and GSK . JRK reports his institution received grant support for clinical trials in pulmonary hypertension from Actelion , Bayer AG , Lung Biotechnology , and United Therapeutics . DL reports honoraria, consultation fees, research support, and/or travel expenses from Actelion, Arena, Bayer AG, Northern Therapeutic, PhaseBio, and United Therapeutics. RN reports Advisory Board member fees from Actelion, Bayer AG, and Lung Biotechnology Corporation, personal fees from Actelion and GSK, and grants from Reata . GS reports grants, personal fees, and non-financial support from Actelion , Bayer AG , GSK , and Merck . HAG reports grants and personal fees from Actelion , Bayer AG , Ergonex , and Pfizer , and personal fees from Gilead, GSK, Merck, and Novartis. PJ reports being an investigator for Actelion and Bayer AG, and personal fees from AOP. SR reports grants and personal fees from Actelion , Bayer AG , Gilead , GSK , Novartis , Pfizer , United Therapeutics , Arena , Ferrer , Merck Sharp & Dohme , and Abbott , and research support from Actelion , Bayer AG , Novartis , Pfizer , and United Therapeutics . LS has nothing to disclose. TT reports personal fees (Advisory Board/CME) from Actelion and Gilead. AR reports honoraria from Bayer AG, research support from United Therapeutics , and consulting fees from St Jude. CM is an employee of Bayer AG. DB was an employee of Chrestos Concept GmBH & Co during writing of the manuscript. MMH reports consultancy fees from Actelion, Bayer AG, and Pfizer, and personal fees from Actelion, Bayer AG, Pfizer, and MSD. Funding Information: RLB reports grants from Bellerophon, Bayer AG, Actelion, and EIGER. PAC reports grants and personal fees (University Research Fund) from Bayer AG, and personal fees from Actelion and GSK. JRK reports his institution received grant support for clinical trials in pulmonary hypertension from Actelion, Bayer AG, Lung Biotechnology, and United Therapeutics. DL reports honoraria, consultation fees, research support, and/or travel expenses from Actelion, Arena, Bayer AG, Northern Therapeutic, PhaseBio, and United Therapeutics. RN reports Advisory Board member fees from Actelion, Bayer AG, and Lung Biotechnology Corporation, personal fees from Actelion and GSK, and grants from Reata. GS reports grants, personal fees, and non-financial support from Actelion, Bayer AG, GSK, and Merck. HAG reports grants and personal fees from Actelion, Bayer AG, Ergonex, and Pfizer, and personal fees from Gilead, GSK, Merck, and Novartis. PJ reports being an investigator for Actelion and Bayer AG, and personal fees from AOP. SR reports grants and personal fees from Actelion, Bayer AG, Gilead, GSK, Novartis, Pfizer, United Therapeutics, Arena, Ferrer, Merck Sharp& Dohme, and Abbott, and research support from Actelion, Bayer AG, Novartis, Pfizer, and United Therapeutics. LS has nothing to disclose. TT reports personal fees (Advisory Board/CME) from Actelion and Gilead. AR reports honoraria from Bayer AG, research support from United Therapeutics, and consulting fees from St Jude. CM is an employee of Bayer AG. DB was an employee of Chrestos Concept GmBH & Co during writing of the manuscript. MMH reports consultancy fees from Actelion, Bayer AG, and Pfizer, and personal fees from Actelion, Bayer AG, Pfizer, and MSD.The RESPITE study was funded by Bayer AG, Berlin, Germany and Merck & Co. Inc. Kenilworth, NJ USA. Medical writing services provided by Robyn Bradbury PhD, of Adelphi Communications Ltd. Macclesfield, UK were funded by Bayer AG, in accordance with Good Publications Practice 3 guidelines. Publisher Copyright: © 2020 The Authors

PY - 2020/10/15

Y1 - 2020/10/15

N2 - Background: RESPITE evaluated patients with pulmonary arterial hypertension and an inadequate response to phosphodiesterase type 5 inhibitors (PDE5i) who switched to riociguat. This post hoc analysis assessed response to this switch in parameters associated with clinical improvement. Methods: RESPITE was a 24-week, uncontrolled pilot study (n = 61). Differences in functional, hemodynamic, and cardiac function parameters, REVEAL risk score (RRS), and biomarkers were compared between responders (free from clinical worsening, World Health Organization functional class I/II, and ≥30 m improvement in 6-min walking distance at Week 24) and non-responders. Results: Of 51 patients (84%) completing RESPITE, 16 (31%) met the responder endpoint. At baseline, there were significant differences between responders and non-responders in N-terminal prohormone of brain natriuretic peptide (NT-proBNP), growth/differentiation factor 15 (GDF-15), and RRS, whereas there were no differences in hemodynamics or cardiac function. At Week 24, responders had significant improvements in pulmonary arterial compliance, pulmonary vascular resistance, and mean pulmonary arterial pressure, while non-responders showed no significant change. Cardiac efficiency and stroke volume index significantly improved irrespective of responder status. Conclusions: NT-proBNP, GDF-15, and RRS were identified as potential predictors of response in patients switching from PDE5i to riociguat. Further prospective controlled studies are needed to confirm the association of these parameters with response.

AB - Background: RESPITE evaluated patients with pulmonary arterial hypertension and an inadequate response to phosphodiesterase type 5 inhibitors (PDE5i) who switched to riociguat. This post hoc analysis assessed response to this switch in parameters associated with clinical improvement. Methods: RESPITE was a 24-week, uncontrolled pilot study (n = 61). Differences in functional, hemodynamic, and cardiac function parameters, REVEAL risk score (RRS), and biomarkers were compared between responders (free from clinical worsening, World Health Organization functional class I/II, and ≥30 m improvement in 6-min walking distance at Week 24) and non-responders. Results: Of 51 patients (84%) completing RESPITE, 16 (31%) met the responder endpoint. At baseline, there were significant differences between responders and non-responders in N-terminal prohormone of brain natriuretic peptide (NT-proBNP), growth/differentiation factor 15 (GDF-15), and RRS, whereas there were no differences in hemodynamics or cardiac function. At Week 24, responders had significant improvements in pulmonary arterial compliance, pulmonary vascular resistance, and mean pulmonary arterial pressure, while non-responders showed no significant change. Cardiac efficiency and stroke volume index significantly improved irrespective of responder status. Conclusions: NT-proBNP, GDF-15, and RRS were identified as potential predictors of response in patients switching from PDE5i to riociguat. Further prospective controlled studies are needed to confirm the association of these parameters with response.

KW - Biomarkers

KW - Pulmonary arterial hypertension

KW - Pulmonary hemodynamics

KW - Right heart function

KW - Riociguat

KW - Switching to riociguat

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DO - 10.1016/j.ijcard.2020.05.044

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AN - SCOPUS:85087207605

SN - 0167-5273

VL - 317

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JO - International Journal of Cardiology

JF - International Journal of Cardiology

ER -

Identifying potential parameters associated with response to switching from a PDE5i to riociguat in RESPITE

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