Researchers evaluated inhaled treprostinil in the phase 3 TETON-1 randomized controlled trial, in which 598 patients with idiopathic pulmonary fibrosis were randomly assigned to treprostinil or placebo to assess the change from baseline in forced vital capacity at 52 weeks.
“Treatment with inhaled treprostinil resulted in a smaller decline in [forced vital capacity (FVC)] and fewer clinical-worsening events than placebo over the course of 52 weeks,” wrote lead researcher Steven D. Nathan, MD, of the Inova Fairfax Hospital in Falls Church, Virginia, and colleagues.
Researchers conducted the double-blind, randomized, placebo-controlled trial at 94 sites in the US and Canada. Eligible patients were aged 40 years or older, had idiopathic pulmonary fibrosis (IPF) diagnosed according to the 2018 American Thoracic Society/European Respiratory Society/Japanese Respiratory Society/Latin American Thoracic Society clinical practice guidelines, and had a FVC of at least 45% of the predicted value. High-resolution computed tomography scans and available surgical lung-biopsy specimens were reviewed centrally.
Patients receiving nintedanib or pirfenidone were required to have received a stable dose for at least 30 days prior to baseline. Patients with a ratio of forced expiratory volume in 1 second to FVC below 0.70 or who required more than 10 L/min of supplemental oxygen at rest were excluded.
Participants were randomly assigned 1:1 to inhaled treprostinil or placebo, with randomization stratified by background antifibrotic therapy. Treatment began at three breaths four times daily and was adjusted to a target of 12 breaths four times daily or the maximum tolerated dose.
The primary endpoint was change in absolute FVC from baseline to week 52. Secondary endpoints were tested in a prespecified sequence to control for multiple comparisons. Clinical worsening was defined as the first occurrence of all-cause death, hospitalization for an adjudicated respiratory cause, or a relative decline of at least 10% in percentage of predicted FVC.
Among 598 patients who underwent randomization and received at least one dose, 299 received treprostinil and 299 received placebo. The mean age was 73 years, 77% were men, and 78% were receiving nintedanib or pirfenidone. A total of 434 patients completed assessments through week 52.
The median change in FVC at week 52 was −43 mL with treprostinil and −196 mL with placebo, with an estimated between-group difference of 130 mL. Sensitivity analyses using alternative methods to account for missing data produced similar findings.
Clinical worsening occurred in 32% of patients receiving treprostinil and 45% receiving placebo. A relative decline of at least 10% in predicted FVC accounted for most first clinical-worsening events, occurring in 68 patients receiving treprostinil and 91 receiving placebo.
No statistically significant difference was observed in time to first acute IPF exacerbation. Under the prespecified testing hierarchy, no further confirmatory conclusions were drawn for the subsequent secondary endpoints.
Cough occurred in 55% of patients receiving treprostinil and 33% receiving placebo. Serious adverse events occurred in 18% and 24%, respectively. Adverse events led to discontinuation of the study drug in 21% of patients receiving treprostinil and 15% receiving placebo.
The researchers noted that the relatively high rate of study-drug discontinuation was a limitation. Overall, study treatment was discontinued in approximately 41% of patients receiving treprostinil and 33% of those receiving placebo. However, sensitivity analyses using different approaches to account for missing data produced similar findings for the primary endpoint.
Disclosures: The study was funded by United Therapeutics. Full disclosures can be found in the published study.
