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.

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

Keywords: Arterial Hypertension; Systemic Lupus Erythematosus; Systemic Sclerosis.

Conflict of interest statement

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.

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