Therapeutic efficacy of Bosentan

A total of 32 and 213 patients were enrolled in the study, and two randomized, double-blind, multicenter, placebo-controlled trials were conducted respectively. The larger trial (BREATHE-1) compared two doses of bosentan (125 mg twice daily; 250 mg twice daily) with placebo; the smaller trial (Study 351) compared bosentan (125 mg twice daily) with placebo.

All enrolled patients had severe pulmonary arterial hypertension (PAH, World Health Organization Functional Class Ⅲ-Ⅳ), with specific types including: idiopathic or heritable PAH (accounting for 72%), PAH associated with scleroderma or other connective tissue diseases (accounting for 21%), and PAH associated with autoimmune diseases (accounting for 7%). Patients with PAH related to other comorbidities (such as human immunodeficiency virus infection, recurrent pulmonary embolism, etc.) were excluded from this study.

In both trials, bosentan treatment significantly improved patients' exercise capacity. After 1 month of treatment (at a dose of 62.5 mg twice daily), the improvement in patients' walking distance was already evident; the improvement was fully manifested after approximately 2 months of treatment and was sustained throughout the 7-month double-blind treatment period.

The improvement in walking distance in the group receiving 250 mg twice daily was slightly greater than that in other dose groups. However, this dose is not recommended because it may increase the risk of hepatotoxicity.

Among subgroups stratified by demographic factors, baseline disease severity, or disease etiology, there were no significant differences in the therapeutic effect on walking distance across different subgroups. However, due to limited study power, the ability of this study to detect such differences was weak.

FDA，2025.07