Efficacy of Inhaled Treprostinil on Multiple Disease Progression Events in Patients with Pulmonary Hypertension Due to Parenchymal Lung Disease in the INCREASE Trial.

Rationale The INCREASE study of inhaled treprostinil met its primary endpoint of change in 6-minute walk distance at Week 16. In addition, there were significantly fewer clinical worsening events in patients receiving inhaled treprostinil. However, the incidence of multiple events in the same patient is unknown. Objectives This post-hoc analysis evaluated the effect of continued treatment with inhaled treprostinil on the frequency and impact of multiple disease progression events. Methods Patients enrolled in INCREASE were analyzed for disease progression events, defined as ≥15% decline in 6-minute walk distance, exacerbation of underlying lung disease, cardiopulmonary hospitalization, lung transplantation, ≥10% decline in forced vital capacity, or death during the duration of the 16-week study. Measurements and Main Results 147 disease progression events occurred in the inhaled treprostinil group (89/163 patients, 55%) compared to 215 events (109/163 patients, 67%) in the placebo group (p=0.018). There was a lower incidence of each disease progression component in the inhaled treprostinil group: 6-minute walk distance decline (45 vs. 64 events), lung disease exacerbation (48 vs. 72 events), forced vital capacity decline (19 vs. 33), cardiopulmonary hospitalization (23 vs. 33 events) and death (10 vs. 12). Fewer patients receiving inhaled treprostinil had multiple progression events compared to placebo (35 vs. 58; 22% vs. 36%, p=0.005). Conclusions Patients who received inhaled treprostinil were significantly less likely to experience further disease progression events after an initial event compared to placebo. These results support the continuation of inhaled treprostinil despite the occurrence of disease progression in clinical practice. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/).