Phase 3 Trials of Inhaled Treprostinil for Idiopathic Pulmonary Fibrosis.

Summary

In a 52‑week, double‑blind phase 3 RCT in IPF (n=598), inhaled treprostinil significantly attenuated FVC decline versus placebo (median difference 130 mL) and reduced clinical worsening (HR 0.67). Safety was acceptable with cough as the most frequent adverse event and higher discontinuation in the active arm.

Key Findings

• Median FVC change at 52 weeks: −43.3 mL with treprostinil vs −196.2 mL with placebo (difference 130.1 mL; 95% CI, 82.2–178.1; P<0.001).
• Clinical worsening occurred in 31.8% (treprostinil) vs 44.5% (placebo); HR 0.67 (95% CI, 0.52–0.88; P=0.003).
• No significant difference in time to IPF exacerbation; cough was the most frequent adverse event (54.8% vs 33.1%).
• High background antifibrotic use (77.6%) with consistent efficacy signals.

Clinical Implications

Inhaled treprostinil can be considered as an add‑on therapy to standard antifibrotics for IPF to slow FVC decline and reduce clinical worsening, with counseling about cough and discontinuation risk.

Limitations

• Higher discontinuation in the active arm and cough as a frequent adverse event may limit tolerability.
• Multiplicity constraints limited inferences beyond selected secondary outcomes; no significant difference in IPF exacerbations.

Future Directions

Define responder subgroups, long‑term outcomes, interaction with specific antifibrotics, and strategies to mitigate cough to improve adherence.