Cassady, Steven J.

ABSTRACT Pulmonary hypertension due to interstitial lung disease (PH‐ILD) is associated with high morbidity and mortality. Real‐world patients initiating inhaled treprostinil are not well‐characterized. This retrospective cohort study aimed to evaluate healthcare resource utilization in patients with PH‐ILD who initiated treatment with inhaled treprostinil vs patients who remained untreated. Adult patients diagnosed with PH‐ILD were indexed on initiation of inhaled treprostinil and patients who remained untreated were indexed on first observed PH diagnosis (31 March 2021–30 September 2024). Patients were excluded if they were ever treated with any pulmonary arterial hypertension therapy. Inhaled treprostinil patients were matched to up to four untreated patients. All‐cause per‐patient per‐month (PPPM) hospitalizations and ICU‐related hospitalizations were the primary outcomes of interest. 294 patients treated with inhaled treprostinil and 736 untreated patients were identified. Mean all‐cause PPPM hospitalizations remained unchanged in the pre‐index vs post‐index periods in the inhaled treprostinil cohort (0.11 vs 0.12; p = 0.42) but significantly increased in untreated patients (0.12 vs 0.23; p < 0.01). ICU utilization also remained unchanged in the pre‐index vs post‐index periods for the inhaled treprostinil cohort (0.06 vs 0.07; p = 0.11) compared to the untreated cohort (0.06 vs 0.13; p < 0.01). Untreated patients had significantly higher post‐index PPPM hospitalizations ( p < 0.01) and ICU utilization ( p < 0.01) compared to inhaled treprostinil patients. Patients who initiated inhaled treprostinil had a 30% decreased risk of hospitalization compared to untreated patients (relative risk: 0.70; 95% CI: 0.59–0.83; p < 0.01). Among real‐world patients with PH‐ILD, treatment with inhaled treprostinil is associated with fewer all‐cause hospitalizations and ICU‐related hospitalizations compared to untreated patients with PH‐ILD.

Background Inhaled treprostinil (iTre) is the only treatment approved for pulmonary hypertension due to interstitial lung disease (PH-ILD) to improve exercise capacity. This post hoc analysis evaluated clinical worsening and PH-ILD exacerbations from the 16-week INCREASE study and change in 6-minute walking distance (6MWD) in the INCREASE open-label extension (OLE) in patients with less severe haemodynamics. Methods Patients were stratified by baseline pulmonary vascular resistance (PVR) of <4 Wood units (WU) versus ≥4 WU and ≤5 WU versus >5 WU. Exacerbations of underlying lung disease, clinical worsening and change in N-terminal prohormone of brain natriuretic peptide (NT-proBNP) in INCREASE were evaluated. For the OLE, patients previously assigned to placebo were considered to have a 16-week treatment delay. 6MWD and clinical events in the OLE were evaluated by PVR subgroup. Results Of the 326 patients enrolled in INCREASE, patients with less severe haemodynamics receiving iTre had fewer exacerbations of underlying lung disease and clinical worsening events. This was supported by the Bayesian analysis of the risk of disease progression (HR<1), and significant decreases in NT-proBNP levels. In the OLE, patients without a treatment delay had improved exercise capacity after 1-year compared with those with a 16-week treatment delay (22.1 m vs −10.3 m). Patients with a PVR of ≤5 WU without a treatment delay had a change of 5.5 m compared with −8.2 m for those with a treatment delay. Patients without a treatment delay had a prolonged time to hospitalisation, lung disease exacerbation and death. Conclusion Treatment with iTre led to consistent benefits in clinical outcomes in patients with PH-ILD and less severe haemodynamics. Earlier treatment in less severe PH-ILD may lead to better exercise capacity long-term, however, the subgroup analyses in this post hoc study were underpowered and confirmation of these findings is needed.