bay-63-2521 and Lung-Diseases--Interstitial

We assessed the safety, tolerability and preliminary efficacy of riociguat, a soluble guanylate cyclase stimulator, in patients with pulmonary hypertension associated with interstitial lung disease (PH-ILD). In this open-label, uncontrolled pilot trial, patients received oral riociguat (1.0-2.5 mg three times daily) for 12 weeks (n=22), followed by an ongoing long-term extension (interim analysis at 12 months) in those eligible (n=15). Primary end-points were safety and tolerability. Secondary end-points included haemodynamic changes and 6-min walk distance (6MWD). Overall, 104 adverse events were reported, of which 25 were serious; eight of the latter were considered drug-related. After 12 weeks of therapy, mean cardiac output increased (4.4 ± 1.5 L · min(-1) to 5.5 ± 1.8 L · min(-1)), pulmonary vascular resistance (PVR) decreased (648 ± 207 dyn · s(-1) · cm(-5) to 528 ± 181 dyn · s(-1) · cm(-5)) and mean pulmonary artery pressure (mPAP) remained unchanged compared with baseline. Arterial oxygen saturation decreased but mixed-venous oxygen saturation slightly increased. The 6MWD increased from 325 ± 96 m at baseline to 351 ± 111 m after 12 weeks. Riociguat was well tolerated by most patients and improved cardiac output and PVR, but not mPAP. Further studies are necessary to evaluate the safety and efficacy of riociguat in patients with PH-ILD.

Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Female; Guanylate Cyclase; Hemodynamics; Humans; Hypertension, Pulmonary; Lung Diseases, Interstitial; Male; Middle Aged; Oxygen; Pilot Projects; Pyrazoles; Pyrimidines; Receptors, Cytoplasmic and Nuclear; Soluble Guanylyl Cyclase; Treatment Outcome

Advances in the treatment of idiopathic interstitial pneumonia (IIP) represent an urgent, unmet medical need for patients with this category of diffuse parenchymal lung disease. IIPs involve varying combinations of fibrosis and inflammation of unknown cause and may be associated with pulmonary hypertension (PH). When it occurs, PH is associated with higher oxygen needs, greater functional impairment, and increased mortality. However, whether or when PH is a maladaptive versus adaptive phenomenon remains to be determined. Despite their differing prognoses, it does appear that the IIPs may follow a similar course once PH supervenes. Therefore, it may be worthwhile to explore studies of PH medications in IIP as a group rather than as individual entities. Such a broad approach eliminates the need to nuance specific diagnoses and thereby facilitates study recruitment and broadens the applicability of the results.

Topics: Cell Proliferation; Clinical Trials as Topic; Enzyme Activators; Extracellular Matrix; Fibroblasts; Humans; Hypertension, Pulmonary; Idiopathic Interstitial Pneumonias; Idiopathic Pulmonary Fibrosis; Lung Diseases, Interstitial; Nitric Oxide; Prognosis; Pyrazoles; Pyrimidines; United States

Topics: Female; Guanylate Cyclase; Humans; Hypertension, Pulmonary; Lung Diseases, Interstitial; Male; Pyrazoles; Pyrimidines