title: Riociguat for the treatment of pulmonary arterial hypertension associated with connective tissue disease: results from PATENT-1 and PATENT-2.
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.
  
  
  BACKGROUND
  PATENT-1 (NCT00810693), PATENT-2 (NCT00863681).
authors.affiliation: Université Paris-Sud, Faculté de Médecine, Université Paris-Saclay, Le Kremlin Bicêtre, France.|AP-HP, Service de Pneumologie, Hôpital Bicêtre, Le Kremlin Bicêtre, France.|Inserm UMR_S 999, Hôpital Marie Lannelongue, Le Plessis Robinson, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Humbert
authors.affiliation: Royal Free London NHS Foundation Trust, London, UK.
authors.forename: J Gerry
authors.initials: JG
authors.lastname: Coghlan
authors.affiliation: University of Giessen and Marburg Lung Center (member of the German Center of Lung Research (DZL)), Giessen, Germany.|Department of Medicine, Imperial College London, London, UK.
authors.forename: Hossein-Ardeschir
authors.initials: HA
authors.lastname: Ghofrani
authors.affiliation: University of Giessen and Marburg Lung Center (member of the German Center of Lung Research (DZL)), Giessen, Germany.
authors.forename: Friedrich
authors.initials: F
authors.lastname: Grimminger
authors.affiliation: Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Jian-Guo
authors.initials: JG
authors.lastname: He
authors.affiliation: Department of Rheumatology, University of Lübeck, Lübeck, Germany.
authors.forename: Gabriela
authors.initials: G
authors.lastname: Riemekasten
authors.affiliation: La Sapienza University of Rome, Rome, Italy.
authors.forename: Carmine Dario
authors.initials: CD
authors.lastname: Vizza
authors.affiliation: Bayer Pharma AG, Wuppertal, Germany.
authors.forename: Annette
authors.initials: A
authors.lastname: Boeckenhoff
authors.affiliation: Bayer Pharma AG, Berlin, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Meier
authors.affiliation: Bayer HealthCare Pharmaceuticals Inc, Whippany, New Jersey, USA.
authors.forename: Janethe
authors.initials: J
authors.lastname: de Oliveira Pena
authors.affiliation: University College London, Royal Free Campus, London, UK.
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Denton
mesh_terms: D000328:Adult; D000368:Aged; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D003240:Connective Tissue Diseases / Q000150:complications; D005260:Female; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy* / Q000209:etiology; D008297:Male; D008875:Middle Aged; D011720:Pyrazoles / Q000627:therapeutic use*; D011743:Pyrimidines / Q000627:therapeutic use*; D012595:Scleroderma, Systemic / Q000150:complications*; D016896:Treatment Outcome; D014655:Vascular Resistance; D000070857:Walk Test
chemical_list: D000959:Antihypertensive Agents; D011720:Pyrazoles; D011743:Pyrimidines; C542595:riociguat
keywords: Arterial Hypertension; Systemic Lupus Erythematosus; Systemic Sclerosis