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FRI0445 Efficacy and Safety of Riociguat in Patients with Pulmonary Arterial Hypertension (PAH) Associated with Connective Tissue Disease (CTD): Results from Patent-1 and Patent-2
  1. C. Denton1,
  2. J.G. Coghlan2,
  3. H.-A. Ghofrani3,
  4. F. Grimminger3,
  5. J. He4,
  6. G. Riemekasten5,
  7. C.D. Vizza6,
  8. A. Boeckenhoff7,
  9. C. Meier8,
  10. S. Nikkho8,
  11. J. Pena9,
  12. M. Humbert10
  1. 1University College London Royal Free Campus
  2. 2Royal Free London NHS Foundation Trust, London, United Kingdom
  3. 3University of Giessen and Marburg Lung Center, Giessen, Germany
  4. 4Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
  5. 5Clinic of Rheumatology and Clinical Immunology, Berlin, Germany
  6. 6La Sapienza University of Rome, Rome, Italy
  7. 7Bayer Pharma AG, Wuppertal
  8. 8Bayer Pharma AG, Berlin, Germany
  9. 9Bayer Pharma AG, Whippany, United States
  10. 10Laboratoire d'Excellence en Recherche sur le Médicament et Innovation Thérapeutique and INSERM Unité 999, Le Kremlin–Bicêtre, Université Paris-Sud, Paris, France

Abstract

Background PAH associated with CTD (PAH-CTD) has a worse prognosis than idiopathic/familial PAH (IPAH).

Objectives Here we report a prospective subgroup analysis of patients (pts) with PAH-CTD from the PATENT studies of the soluble guanylate cyclase stimulator, riociguat.

Methods PATENT-1 was a 12-wk, randomized Phase III trial in which pts with PAH received either riociguat individually dose-adjusted up to 2.5 mg tid (2.5 mg–maximum group), riociguat up to 1.5 mg tid (1.5 mg–maximum group; exploratory), or placebo (pbo). The primary endpoint was change from baseline in 6-minute walking distance (6MWD). Long-term safety and survival were assessed during the PATENT-2 open-label extension.

Results In PATENT-1, 111 pts had PAH-CTD (systemic sclerosis [SSc; n=66, including diffuse SSc and limited SSc] non-SSc CTD [n=39], and unspecified CTD [n=6], derived from the medical history using MedDRA preferred terms). Of the overall group of PAH-CTD pts, 71, 15, and 25 were randomized to riociguat 2.5 mg–maximum, riociguat 1.5 mg–maximum, and pbo, respectively. At baseline, mean ± SD 6MWD was 348±70 m in the riociguat 2.5 mg–maximum group and 361±88 m in the pbo group versus 363±69 m in the overall PAH population. At Wk 12, there was an improvement in 6MWD in the 2.5 mg–maximum riociguat group (+18 m) and a deterioration in the pbo group (–8 m) (Figure 1a; PAH-CTD population; intention-to-treat [ITT], imputed values). Consistent with other studies, the least-squares mean treatment difference between riociguat and pbo (+28 m) was lower than that observed in the overall study population (+36 m). No pts in the riociguat 2.5 mg–maximum group required additional PAH therapy during PATENT-1, compared with 2 pts in the pbo group. At the March 2014 cut-off for PATENT-2, 70 pts with PAH-CTD had been receiving treatment for ≥2 yrs. Figure 1b shows change in 6MWD during PATENT-2 in pts with PAH-CTD. At 2 yrs, mean ± SD 6MWD had increased from PATENT-1 baseline by 25±82 m in pts with PAH-CTD versus 47±85 m in the overall population (ITT; observed values). Survival rates at 1 yr in pts with PAH-CTD, IPAH, and the overall population were 97% (95% CI: 90–99%), 98% (95% CI: 95–99%), and 97% (95% CI: 95–98%), respectively. Survival rates at 2 yrs were 93% in all cohorts (95% CI: 85–97%, 89–96%, and 90–95%, respectively). Riociguat had a similar safety profile in pts with PAH-CTD as observed in the overall population.

Conclusions In pts with PAH-CTD, riociguat was associated with long-term improvements in exercise capacity. The 1- and 2-yr survival rates in riociguat-treated pts with PAH-CTD were high and similar to pts with IPAH.

Disclosure of Interest C. Denton Consultant for: Bayer, Speakers bureau: Novertis, Pfizer, J. Coghlan: None declared, H.-A. Ghofrani Consultant for: Novertis, Pfizer, Speakers bureau: Novertis, Pfizer, F. Grimminger: None declared, J. He: None declared, G. Riemekasten Consultant for: Bayer, Speakers bureau: Bayer, C. Vizza Grant/research support from: Bayer, Actelion, GSK, Novartis, Gilead, Consultant for: Bayer, Actelion, GSK, Utel, A. Boeckenhoff Employee of: Bayer Pharma AG, C. Meier Employee of: Bayer Pharma AG, S. Nikkho Employee of: Bayer Pharma AG, J. Pena Employee of: Bayer Pharma AG, M. Humbert Consultant for: Novartis, Pfizer, GSK, Actelion, Bayer, Speakers bureau: Novartis, Pfizer, GSK, Actelion, Bayer

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