N Engl J Med 2021 Jan 13
Inhaled Treprostinil in Pulmonary Hypertension Due to Interstitial Lung Disease.
Abstract
Background
No therapies are currently approved for the treatment of pulmonary hypertension in patients with interstitial lung disease. The safety and efficacy of inhaled treprostinil for patients with this condition are unclear.
Methods
We enrolled patients with interstitial lung disease and pulmonary hypertension (documented by right heart catheterization) in a multicenter, randomized, double-blind, placebo-controlled, 16-week trial. Patients were assigned in a 1:1 ratio to receive inhaled treprostinil, administered by means of an ultrasonic, pulsed-delivery nebulizer in up to 12 breaths (total, 72 μg) four times daily, or placebo. The primary efficacy end point was the difference between the two groups in the change in peak 6-minute walk distance from baseline to week 16. Secondary end points included the change in N-terminal pro-B-type natriuretic peptide (NT-proBNP) level at week 16 and the time to clinical worsening.
Results
A total of 326 patients underwent randomization, with 163 assigned to inhaled treprostinil and 163 to placebo. Baseline characteristics were similar in the two groups. At week 16, the least-squares mean difference between the treprostinil group and the placebo group in the change from baseline in the 6-minute walk distance was 31.12 m (95% confidence interval [CI], 16.85 to 45.39; P<0.001). There was a reduction of 15% in NT-proBNP levels from baseline with inhaled treprostinil as compared with an increase of 46% with placebo (treatment ratio, 0.58; 95% CI, 0.47 to 0.72; P<0.001). Clinical worsening occurred in 37 patients (22.7%) in the treprostinil group as compared with 54 patients (33.1%) in the placebo group (hazard ratio, 0.61; 95% CI, 0.40 to 0.92; P = 0.04 by the log-rank test). The most frequently reported adverse events were cough, headache, dyspnea, dizziness, nausea, fatigue, and diarrhea.
Conclusions
In patients with pulmonary hypertension due to interstitial lung disease, inhaled treprostinil improved exercise capacity from baseline, assessed with the use of a 6-minute walk test, as compared with placebo. (Funded by United Therapeutics; INCREASE ClinicalTrials.gov number, NCT02630316.).
Related Questions
How do you determine if pulmonary hypertension is disproportionate to the severity of lung disease?
This is a question we faced on a daily basis in our PH clinic. Patients with parenchymal lung disease like COPD or ILD would get an echocardiogram that showed an elevated RVSP and/or RV dilation/dysfunction and will be referred to our clinic for PH evaluation. Alternatively, the patient already unde...
When do you screen for pulmonary hypertension in ILD patients?
Pulmonary hypertension (PH) is a frequent finding in patients with advanced interstitial lung disease (ILD) and its presence is associated with worse morbidity and mortality. The prevalence of PH will depend on the severity of ILD, ranging from around 10% at diagnosis and about 60% of patients with ...
Based on findings of the INCREASE trial, are you routinely prescribing inhaled treprostinil to patients with group 3 pulmonary hypertension secondary to interstitial lung disease?
As a brief background, the INCREASE trial (Waxman et al., PMID 33440084) was a randomized trial in patients with pulmonary hypertension due to interstitial lung disease (PH-ILD) assessing the effect of inhaled treprostinil versus placebo on change in 6-minute walk distance at 16 weeks. The study enr...