Inhaled treprostinil for idiopathic pulmonary fibrosis

Treprostinil is a synthetic analogue of prostacyclin that acts as a direct vasodilator for pulmonary and systemic vascular beds and inhibits platelet aggregation.

The INCREASE study was a randomised, double-blind, placebo-controlled, phase 3 trial (RCT) that evaluated the effectiveness of inhaled on exercise tolerance in patients with pulmonary hypertension secondary to interstitial lung disease (1):

• inhaled treprostinil was associated with a significant placebo-corrected improvement in the primary end-point of 6-min walk distance (6MWD) of 31.1 m (95% CI 16.9–45.4 m; p<0.001) at week 16
• inhaled treprostinil led to improvements compared with placebo in important secondary end-points, including decreased plasma N-terminal pro-brain natriuretic peptide (NT-proBNP) and decreased occurrence of clinical worsening

In the TETON-2 trial investigating the use of trepostinil in patients with idiopathic pulmonary fibrosis (2):

• over a 52-week period, randomised controlled trial (n=593) found inhaled treprostinil linked to a smaller decline in FVC than placebo over 52 weeks (median change: −49.9ml [95% CI, −79.2 to −19.5 vs. −136.4ml [−172.5 to −104.0), respectively, difference 95.6ml [52.2 to 139.0]; P<0.001) and fewer clinical-worsening events
• most common adverse event was cough, reported in 48.3% of the patients in the treprostinil group and 24.1% of those in the placebo group

In a combined analysis of the results of the TETON-1 and TETON-2 trials, the study authors concluded (3):

• in patients with idiopathic pulmonary fibrosis, treatment with inhaled treprostinil led to a smaller decline in FVC and fewer clinical-worsening events than placebo over the course of 52 weeks

References:

1. Waxman A et al. Inhaled Treprostinil in Pulmonary Hypertension Due to Interstitial Lung Disease. N Engl J Med. 2021 Jan 28;384(4):325-334.
2. Nathan SD et al; TETON-2 Trial Investigators. Inhaled Treprostinil for Idiopathic Pulmonary Fibrosis. N Engl J Med. 2026 Mar 11.
3. Nathon SD et al; Phase 3 Trials of Inhaled Treprostinil for Idiopathic Pulmonary Fibrosis. N Engl J Med. 2026 May 18.