Inhaled Treprostinil in Pulmonary Hypertension in the Context of Interstitial Lung Disease: A Success, Finally

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 at least 15% decline in 6-minute-walk distance, exacerbation of underlying lung disease, cardiopulmonary hospitalization, lung transplantation, at least 10% decline in forced vital capacity, or death during the duration of the 16-week study. Measurements and Main Results In total, 147 disease progression events occurred in the inhaled treprostinil group (89/163 patients, 55%) compared with 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), FVC 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 with those receiving the 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 with patients receiving placebo. These results support the continuation of inhaled treprostinil despite the occurrence of disease progression in clinical practice.