Results
LUNG, COMBINED PULMONARY FIBROSIS AND EMPHYSEMA, EVENT, ADVERSE EVENT, CONNECTIVE TISSUE DISEASE
The INCREASE study enrolled 326 patients with PH resulting from ILD who were randomized equally to receive iTre or placebo in a double-blind fashion. The baseline characteristics of the study cohort have been described previously.Consolidated Standards of Reporting Trials diagram depicting patient disposition based on dosage. AE = adverse event.Baseline Demographics, Hemodynamics, and Lung Function of the Four Groups at the Start of the INCREASE StudyData are presented as No. (%) or median (range), unless otherwise indicated. 6MWD = 6-min walk distance; bps = breaths per session; CPFE = combined pulmonary fibrosis and emphysema; CTD = connective tissue disease; DCochran-Mantel-Haenszel test for categorical variables and stratified Wilcoxon (van Elteren) test for continuous variables.Bar graph showing the distribution of dosages at week 4.Forty patients in the iTre < 9 bps group uptitrated to iTre ≥ 9 bps between weeks 4 and 16, whereas four patients downtitrated from iTre ≥ 9 bps to iTre < 9 during this period. For the placebo arm, 45 and 3 patients, respectively, switched groups (Twelve of 70 patients (17.1%) in the iTre ≥ 9 bps group experienced a clinical worsening event between weeks 4 and 16 vs 18 of 79 patients (22.8%) in the iTre < 9 bps group vs 29 of 86 patients (33.7%) and 23 of 67 patients (34.3%) in the placebo ≥ 9 bps and < 9 bps groups, respectively (Clinical Worsening and Clinical Improvement in the Four Groups of Patients (Defined at Week 4) at Week 16Data are presented as No. (%), unless otherwise indicated. 6MWD = 6-min walk distance; bps = breaths per session; iTre = inhaled treprostinil.Cochran-Mantel-Haenszel test adjusted for baseline 6MWD category.Defined by a 15% increase in 6MWD accompanied by a 30% decrease in N-terminal prohormone of brain natriuretic peptide in the absence of any clinical worsening.Bar graphs showing clinical improvement and clinical worsening in patients who were receiving iTre ≥ 9 bps four times daily vs iTre < 9 bps four times daily vs the two placebo groups (combined for this figure): based on groupings at week 4 (A) and based on the last dosage groupings (B). iTre = inhaled treprostinil.As a sensitivity analysis, we analyzed patients for any clinical worsening event or improvement grouped by last dosage received. For this analysis, we also included only patients who made it to week 4 for consistency with the primary analysis (Clinical Worsening and Clinical Improvement After Week 4 by Groups Defined by the Last Dosage ReceivedData are presented as No. (%), unless otherwise indicated. 6MWD = 6-min walk distance; bps = breaths per session; iTre = inhaled treprostinil.Cochran-Mantel-Haenszel test adjusted for baseline 6MWD category.Defined by a 15% increase in 6MWD accompanied by a 30% decrease in N-terminal prohormone of brain natriuretic peptide in the absence of any clinical worsening.