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  • Riociguat for the treatment of pulmonary arterial hypertension associated with connective tissue disease: results from PATENT-1 and PATENT-2

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Clinical and epidemiological research
Concise report
Riociguat for the treatment of pulmonary arterial hypertension associated with connective tissue disease: results from PATENT-1 and PATENT-2
  1. Marc Humbert1,2,3,
  2. J Gerry Coghlan4,
  3. Hossein-Ardeschir Ghofrani5,6,
  4. Friedrich Grimminger5,
  5. Jian-Guo He7,
  6. Gabriela Riemekasten8,
  7. Carmine Dario Vizza9,
  8. Annette Boeckenhoff10,
  9. Christian Meier11,
  10. Janethe de Oliveira Pena12,
  11. Christopher P Denton13
  1. 1Université Paris-Sud, Faculté de Médecine, Université Paris-Saclay, Le Kremlin Bicêtre, France
  2. 2AP-HP, Service de Pneumologie, Hôpital Bicêtre, Le Kremlin Bicêtre, France
  3. 3Inserm UMR_S 999, Hôpital Marie Lannelongue, Le Plessis Robinson, France
  4. 4Royal Free London NHS Foundation Trust, London, UK
  5. 5University of Giessen and Marburg Lung Center (member of the German Center of Lung Research (DZL)), Giessen, Germany
  6. 6Department of Medicine, Imperial College London, London, UK
  7. 7Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
  8. 8Department of Rheumatology, University of Lübeck, Lübeck, Germany
  9. 9La Sapienza University of Rome, Rome, Italy
  10. 10Bayer Pharma AG, Wuppertal, Germany
  11. 11Bayer Pharma AG, Berlin, Germany
  12. 12Bayer HealthCare Pharmaceuticals Inc, Whippany, New Jersey, USA
  13. 13University College London, Royal Free Campus, London, UK
  1. Correspondence to Professor Christopher P Denton, Centre for Rheumatology, UCL Division of Medicine, Rowland Hill Street, London NW3 2PF, UK; c.denton{at}ucl.ac.uk

Abstract

Background The 12-week, phase III Pulmonary Arterial hyperTENsion sGC-stimulator Trial (PATENT)-1 study investigated riociguat in patients with pulmonary arterial hypertension (PAH). Here, we present a prospectively planned analysis of the safety and efficacy of riociguat in the subgroup of patients with PAH associated with connective tissue disease (PAH-CTD).

Methods Patients with PAH-CTD were further classified post hoc as having PAH associated with systemic sclerosis or PAH-other defined CTD. In PATENT-1, patients received riociguat (maximum 2.5 or 1.5 mg three times daily) or placebo. Efficacy endpoints included change from baseline in 6-minute walking distance (6MWD; primary endpoint), haemodynamics and WHO functional class (WHO FC). In the long-term extension PATENT-2, patients received riociguat (maximum 2.5 mg three times daily); the primary endpoint was safety and tolerability.

Results In patients with PAH-CTD, riociguat increased mean 6MWD, WHO FC, pulmonary vascular resistance and cardiac index. Improvements in 6MWD and WHO FC persisted at 2 years. Two-year survival of patients with PAH-CTD was the same as for idiopathic PAH (93%). Riociguat had a similar safety profile in patients with PAH-CTD to that of the overall population.

Conclusions Riociguat was well tolerated and associated with positive trends in 6MWD and other endpoints that were sustained at 2 years in patients with PAH-CTD.

Trial registration numbers PATENT-1 (NCT00810693), PATENT-2 (NCT00863681).

  • Systemic Sclerosis
  • Systemic Lupus Erythematosus
  • Arterial Hypertension

This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/

https://doi.org/10.1136/annrheumdis-2015-209087

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    Footnotes

    • Handling editor Tore K Kvien

    • Contributors MH, JGC, H-AG, FG, J-GH and CDV were PATENT-1 investigators directly involved in the recruitment and care of the participants; CPD, MH and CM contributed to the post hoc classification of patients; all authors contributed to the analysis and interpretation of the data, and contributed to the writing and revision of the manuscript for intellectual content, and have reviewed and approved the final version for submission.

    • Funding This study was supported by Bayer Pharma AG, Berlin, Germany. Editorial support was provided by Adelphi Communications Ltd, Bollington, UK, supported by Bayer Pharma AG.

    • Competing interests MH has received grants or fees for congress participation, advisory and expert board meetings, and/or research from Actelion, Bayer, GSK, Novartis and Pfizer, all related to the development of drugs in the field of pulmonary hypertension. CPD has been a consultant to Bayer, Roche, GSK, Actelion, Inventiva, CSL Behring, Takeda, Merck-Serono, MedImmune and Biogen. He has received research grants from Actelion, GSK, Novartis and CSL Behring. JGC has received consultancy fees and honoraria from Actelion, GSK, Bayer, United Therapeutics, Endotronics and Pfizer, and unrestricted grants from Actelion, and GSK. J-GH has received fees for participation in advisory boards from Bayer. CDV has received grants or fees for congress participation, advisory boards and research from Actelion, Bayer, GSK, Lilly, Pfizer, and UTEL. AB and CM are employees of Bayer Pharma AG. JdOP is an employee of Bayer HealthCare Pharmaceuticals.

    • Ethics approval The Institutional Review Board at each participating centre approved the protocol. Data were collected according to Good Clinical Practice guidelines at the investigation sites.

    • Provenance and peer review Not commissioned; externally peer reviewed.