Riociguat’s Broad Positive Impact Includes PAH-Associated with Connective Tissue Disease

A prospective analysis of two clinical trials, PATENT-1 and PATENT-2, showed that riociguat (Adempas) treatment improves several parameters of lung and cardiac function in patients with pulmonary arterial hypertension (PAH), and in those with PAH associated with connective tissue disease (PAH-CTD).

The study “Riociguat for the treatment of pulmonary arterial hypertension associated with connective tissue disease: results from PATENT-1 and PATENT-2,” was published in the journal Annals of the Rheumatic Diseases.

Riociguat, a novel drug that stimulates soluble guanylate cyclase (a key signal-transduction enzyme activated by nitric oxide), is approved for the treatment of PAH. The drug was shown to carry several properties including antifibrotic, antiproliferative and anti-inflammatory effects in preclinical models.

In the Phase 3 Pulmonary Arterial hyperTENsion sGC-stimulator Trial (PATENT)-1 study (NCT00810693), researchers investigated the effects of riociguat in patients with PAH. The trial results showed riociguat as well-tolerated and that it improved the 6-minute walking distance (6MWD) test to assess exercise capacity. Several secondary outcomes that included pulmonary vascular resistance were also noted.

The benefits of riociguat in 6MWD and the World Health Organization’s functional class (WHO FC) were further assessed in the  follow-up trial, the PATENT-2 open-label extension study (NCT00863681).

For the newest report, researchers performed a prospective analysis and evaluated both safety and efficacy of riociguat in a specific subgroup of PAH patients included in the PATENT-1 and PATENT-2 studies, those with PAH-CTD which is considered a life threatening complication of connective tissue diseases. In PATENT-1, patients received riociguat (maximum 2.5 or 1.5 mg three times daily) or placebo; the PATENT-2 study patients were treated with riociguat (maximum 2.5 mg three times daily).

Patients with PAH-CTD were further classified and distinguished by those with PAH associated with systemic sclerosis (SSc) or PAH-associated with other defined CTD.

Researchers discovered that patients with PAH-CTD treated with riociguat showed an increase in mean 6MWD, WHO FC, pulmonary vascular resistance and cardiac index (heart performance according to the size of the individual). Improvements in both 6MWD and WHO FC were detected for up to 2 years. The survival rates for patients with PAH-CTD showed the same as patients with idiopathic PAH, 93%.

The research team concluded: “Riociguat was well tolerated in patients with PAH-CTD and led to improvement or stabilization in 6MWD, WHO FC and hemodynamics. The 2-year survival rate of patients with PAH-CTD or PAH-SSc was similar to that of patients with idiopathic/familial PAH.”