Inhaled Treprostinil in Patients with Pulmonary Hypertension Due to Interstitial Lung Disease

Pulmonary hypertension (PH) is a common complication of interstitial lung disease (ILD) and is associated with worse functional status and survival. There are limited effective treatments for PH-ILD, and prior trials with oral PH-specific therapies have shown mixed or negative results.

The INCREASE trial was a phase 3, randomized, double-blind, placebo-controlled trial. It enrolled 326 patients with PH due to ILD (Group 3 PH) and randomized them to receive inhaled treprostinil or placebo for 16 weeks. The primary endpoint was the change from baseline to week 16 in the 6-minute walk distance (6MWD).

Inhaled treprostinil significantly improved the 6MWD at week 16 compared to placebo (mean difference 33.0 meters, 95% CI 20.1 to 45.9, p<0.001). Treatment with treprostinil also led to significant improvements in forced vital capacity (FVC) (mean difference 2.2%, 95% CI 0.7 to 3.7, p=0.004) and NT-proBNP levels (median ratio 0.85, 95% CI 0.76 to 0.94, p=0.002). The most common adverse events with treprostinil were cough, headache, and dizziness.

Inhaled treprostinil is an effective therapy for improving exercise capacity and lung function in patients with pulmonary hypertension due to interstitial lung disease. This represents a significant advancement, offering a new treatment option for a previously underserved patient population.

The study duration was relatively short (16 weeks), limiting conclusions about long-term efficacy and safety. The primary endpoint, 6MWD, is a surrogate marker and may not directly translate to improved survival or quality of life. The trial excluded patients with severe ILD or severe PH.