Riociguat improves exercise capacity in sarcoidosis-associated pulmonary hypertension

Riociguat treatment significantly improved exercise capacity and prevented clinical worsening in patients with sarcoidosis-associated pulmonary hypertension, according to study results published in Chest.

“To date, no placebo-controlled trial has evaluated treatment of sarcoidosis-associated pulmonary hypertension using time to clinical worsening as either a primary or a secondary endpoint,” Robert P. Baughman, MD, professor in the department of internal medicine at the University of Cincinnati Medical Center, and colleagues wrote. “Riociguat is a soluble guanylate cyclase stimulator that has been shown to be a successful treatment for WHO group 1 pulmonary arterial hypertension and WHO group 4 chronic thromboembolic pulmonary hypertension.”

The 1-year, double-blind, placebo-controlled, randomized controlled trial enrolled 16 patients with sarcoidosis-associated pulmonary hypertension confirmed by right heart catheterization. All patients were randomly assigned riociguat (Adempas, Bayer; n = 8; mean age, 52 years; 66.6% women) or placebo (n = 8; mean age, 64 years; 100% women) and underwent 6-minute walk distance and spirometry testing every 8 weeks.

The primary outcome was time to clinical worsening, defined as the time to all-cause mortality or first hospitalization due to worsening cardiopulmonary status attributable to disease progressor, a more than 50 m decrease in the 6-minute walk distance test or worsening of WHO functional class.

Researchers observed no differences in pulmonary artery mean, pulmonary vascular resistance, initial 6-minute walk distance or FVC. Five patients in the placebo group met time to clinical worsening criteria whereas no patients treated with riociguat experienced any time to clinical worsening criteria.

The placebo group experienced a decrease in 6-minute walk distance, whereas patients treated with riociguat experienced an increase in 6-minute walk distance (median, –55.9 m vs. 42.7 m; P = .0149), with a placebo-corrected difference of 94 m (P < .01). In addition, half of the patients receiving riociguat had an improvement in 6-minute walk distance of more than 30 m compared with one of the patients in the placebo group (P > .05).

Patients receiving riociguat reported no significant adverse events associated with treatment and participated in the study for a longer period compared with patients who received the placebo (P = .0124).

“This supports the implementation of a larger phase 3 clinical trial of riociguat for this specific indication with a number of lessons to be learned from this small study in the design of any such future program,” the researchers wrote.