RESULTS
TYVASO increased exercise capacity to help patients with PH-ILD walk farther1,2
At week 16 in the Hodges-Lehmann analysis, patients who took TYVASO had a placebo-corrected median difference in peak 6MWD of 21 m1
Change in 6MWD (m) from baseline through week 161,2*†‡
Hodges-Lehmann placebo-corrected median difference.
Patients who took TYVASO saw improvement in 6MWD starting as early as week 4 and reached statistical significance by week 12.1
TYVASO improved 6MWD across a range of PH-ILD subgroups.1§
*Weeks 4 and 8 were exploratory endpoints and weeks 12 and 15 were secondary endpoints.2
† P values were obtained from nonparametric ANCOVA adjusted for baseline 6MWD category.2
‡At week 15 (trough), patients who took TYVASO had a placebo-corrected median difference in 6MWD of 15 m (P=0.04).2
§Benefits were observed across several subgroups, including etiology of PH-ILD, disease severity (measured by baseline 6MWD), age, sex, baseline hemodynamics, and dose group.1
A sensitivity analysis supports the finding that patients with PH-ILD who took TYVASO walked farther3,4
At week 16 in the MMRM analysis, patients who took TYVASO had a placebo-corrected mean difference in peak 6MWD of 31 m3
Change in peak 6MWD (m) from baseline through week 163,4||¶
MMRM placebo-corrected LS mean difference.
MMRM analysis was a prespecified sensitivity analysis for the primary endpoint.4
MMRM uses all available data at all timepoints and does not require imputation of individual missing data points. In Hodges-Lehmann methodology, imputed walk of 0 m was assigned for death, clinical worsening event, and too ill to perform 6MWT. The last observation was carried forward for all other reasons.2
|| LS mean, P values, and estimated difference were from the MMRM with the change from baseline in peak 6MWD as the dependent variable; treatment, week, and treatment-by-week interaction as the fixed effects; baseline 6MWD as the covariate; and subject as the random effect.4
¶At week 15 (trough), patients who took TYVASO had a placebo-corrected LS mean difference in 6MWD of 22 m (P=0.004).3
During the 16-week study, TYVASO reduced the risk of a clinical worsening event by 39%1,3**††
Time to first clinical worsening event1,2
Clinical worsening events included a hospitalization due to a cardiopulmonary indication (11% TYVASO vs 14.7% placebo); a decrease in 6MWD >15% from baseline (8% TYVASO vs 16% placebo); death–all causes (2.5% TYVASO vs 2.5% placebo); or lung transplantation (1.2% TYVASO vs 0% placebo).1
**Overall, incidence of any clinical worsening event was 22.7% for patients who took TYVASO vs 33.1% for those who took placebo (P=0.04).3
††Patients who discontinued from the study early had their time to clinical worsening censored at their last visit. Patients who did not experience a clinical worsening event had their time to clinical worsening censored at the study termination date.2
‡‡ P value was calculated with log-rank test stratified by baseline 6MWD category.2
§§HR, 95% CI, and P value were calculated with proportional hazards model with treatment and baseline 6MWD (continuous) as explanatory variables.2
TYVASO reduced NT-proBNP, a biomarker associated with RV dysfunction3,5
At week 16, TYVASO resulted in a 15% reduction in NT-proBNP compared with a 46% increase for placebo (P<0.001)3|| ||
NT-proBNP: Change from baseline (%)3,4
The role of NT-proBNP in PH-ILD and the clinical significance of changes associated with therapy are unknown.
|| || P value was obtained from the MMRM analysis with the change from baseline in log-transformed NT-proBNP as the dependent variable; treatment, week, and treatment-by-week interaction as the fixed effects; and log-transformed baseline NT-proBNP as the covariate.4
NOTE: Elevated levels of BNP and NT-proBNP are biomarkers that can indicate RV dysfunction. Levels correlate to the severity of cardiac stress and begin to increase before symptoms of severe PH and heart failure (eg, peripheral edema, weight gain) are present.5
6MWD=6-minute walk distance; 6MWT=6-minute walk test; ANCOVA=analysis of covariance; CI=confidence interval; HR=hazard ratio; LS=least squares; MMRM=mixed-effect model repeat measurement; NT-proBNP=N-terminal pro−B-type natriuretic peptide; RV=right ventricular.
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