SESSION TITLE: Pulmonary Vascular Disease Posters SESSION TYPE: Original Investigation Posters PRESENTED ON: October 18-21, 2020 PURPOSE: Inhaled treprostinil (iTRE) is approved for the treatment of Group 1 pulmonary hypertension (PH). Group 3 includes PH as a result of interstitial lung disease (PH-ILD). In preclinical studies, treprostinil has been shown to impact extracellular matrix remodeling and development of fibrosis. INCREASE evaluated the safety and efficacy of iTRE in PH-ILD patients. Post-hoc analyses were conducted on the impact of iTRE on lung function. METHODS: INCREASE was a multicenter, randomized, double-blind, placebo-controlled, 16-week study. Inclusion criteria included diagnosis by right heart catheterization and computed tomography imaging. Patients receiving treatment for underlying lung disease were on a stable and optimized dose. Exacerbation of underlying lung disease (acute, clinically significant, respiratory deterioration accompanied by evidence of new widespread alveolar abnormality) was assessed. Pulmonary function testing was conducted at Weeks 8 and 16. This analysis provides further detail on effects on forced vital capacity (FVC), the most widely accepted lung function measurement for evaluation of fibrotic lung disease. RESULTS: 326 patients were enrolled. PH-ILD etiology included idiopathic interstitial pneumonia (45%; 28% idiopathic pulmonary fibrosis), combined pulmonary fibrosis and emphysema (25%), and connective tissue disease (22%). A minority of patients received either pirfenidone (14%) or nintedanib (9%). iTRE patients experienced significantly fewer exacerbations of underlying lung disease (34% risk reduction compared to placebo; p=0.018). FVC improved with iTRE by 28.47 mL and 44.4 mL at Weeks 8 and 16, respectively, when compared to placebo. Percent predicted FVC also improved at Weeks 8 (1.79%; p=0.0139) and 16 (1.8%; p=0.0277). Subgroup analysis of patients with idiopathic interstitial pneumonia (N=146) demonstrated FVC improvements of 46.48 mL and 108.18 mL (p=0.0229) at Weeks 8 and 16, respectively, and improvements in % predicted FVC at Weeks 8 (1.95%, p=0.0373) and 16 (2.88%; p=0.0096) compared to placebo. Further analysis for patients with idiopathic pulmonary fibrosis (N=92) demonstrated FVC improvements of 84.52 mL and 168.52 mL (p=0.0108) at Weeks 8 and 16, respectively, and improvements in % predicted FVC at Weeks 8 (2.54%; p=0.038) and 16 (3.5%; p=0.0147) compared to placebo. CONCLUSIONS: iTRE was not associated with any decrement in lung function during the course of the study. Findings of improvement in underlying lung disease (improved FVC and fewer exacerbations), combined with the preclinical evidence of antifibrotic activity of treprostinil, suggest that iTRE may offer a treatment option for patients with ILD. CLINICAL IMPLICATIONS: Study results support an additional treatment avenue and might herald a shift in the clinical management of patients with ILD. Further consideration should be given to investigation of iTRE in patients with ILD in the absence of PH. 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