Inhaled treprostinil safe, improves outcomes in pulmonary hypertension-ILD over 1 year
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Key takeaways:
- Six-minute walk distance improved over 52 weeks with inhaled treprostinil.
- Lung function, as measured by FVC, also improved at week 64 with the drug.
Inhaled treprostinil was safe in patients with pulmonary hypertension associated with interstitial lung disease over 1 year and sustained improved exercise capacity, according to study results published in European Respiratory Journal.
“I hope the impact of this trial and the clear benefit on everyday clinicians is greater awareness so that they look for the disease,” Aaron B. Waxman, MD, PhD, FACP, FCCP, director of the pulmonary vascular disease program at Brigham and Women’s Hospital, told Healio. “I would encourage screening for pulmonary hypertension (PH) in those patients who have a reduced diffusing capacity of the lung for carbon monoxide out of proportion to their lung CT findings or functional status. I also would encourage lowering the threshold for right heart catheterization so that we can get these patients treated as early as possible which should impact their quality of life and overall course.”
In an open-label extension of the INCREASE study, Waxman and colleagues analyzed 242 patients (median age, 70 years; 52.1% men) with PH-ILD from the study cohort receiving inhaled treprostinil (Tyvaso, United Therapeutics) to measure 6-minute walk distance (6MWD), FVC, N-terminal pro-brain natriuretic peptide (NT-proBNP), quality of life and adverse events at week 64.
As Healio previously reported, patients with PH-ILD in the phase 3, multicenter, randomized, double-blind, placebo-controlled INCREASE study had significantly improved exercise capacity and other clinical outcomes over 16 weeks with inhaled treprostinil.
Additionally, a post-hoc analysis of the INCREASE study found better outcomes with a higher dose of inhaled treprostinil compared with a lower dose or placebo.
In this study, 119 patients continued to receive the drug as they did in the original study, whereas 121 patients had previously received placebo and two patients were not from the INCREASE study.
When accounting for all patients, 62.1 weeks was the median duration of exposure to the drug, but researchers found longer exposure in the inhaled treprostinil group vs. the previous placebo group (77.3 weeks vs. 47 weeks).
Similar to the original study, researchers found an increase in mean 6MWD with inhaled treprostinil at week 52 vs. baseline (279.1 m vs. 274.2 m). When separated according to their prior group in the original study, those who previously received inhaled treprostinil improved their 6MWD by 22.1 m at week 52, whereas those who previously received placebo had a lower 6MWD (mean change from INCREASE RCT baseline, –19.5 m).
Researchers additionally observed improvements in NT-proBNP at week 64 (week 64 median, 359 pg/mL–1 vs. baseline, 389 pg/mL–1), as well as in absolute percent predicted mean FVC by 2.8%, of which the latter was unexpected, Waxman told Healio.
“[I am] not sure why the FVC is improved but would hypothesize that it is related to improved vascular compliance or improved respiratory muscle function,” he said.
For quality of life, researchers used the St. George’s Respiratory Questionnaire and assessed distance-saturation product, both of which did not worsen.
When evaluating exacerbations of underlying lung disease, researchers found a 31% decreased risk in the previously inhaled treprostinil group when assessed against the previously placebo group (HR = 0.69; 95% CI, 0.49-0.97; P = .0321).
“The most surprising and unexpected findings were the sustained delay in clinical worsening and reduction in exacerbations,” Waxman told Healio.
Of the total cohort, 133 patients experienced a serious adverse event, and 54 patients (22.3%) stopped receiving inhaled treprostinil due to an adverse event. According to researchers, more patients from the previously placebo group discontinued the drug for this reason compared with patients from the previously inhaled treprostinil group (28.1% vs. 16.8%).
Patients frequently experienced cough, dyspnea and headache, which were comparable to the initial study.
Researchers observed cardiopulmonary hospitalizations in 76 patients (31.4%) and mortality in 62 patients (25.6%), of which 29 received the drug in the original study and 33 received placebo. Notably, the time to death was longer in the previously inhaled treprostinil group vs. the previously placebo group (median, 62 weeks vs. 31.3 weeks).
“Future studies will be different because now there is a treatment, and patients going into future studies will likely need to be on background therapy first,” Waxman told Healio. “This may make future trials a little harder, especially if it is dependent on a 6MWD.”
For more information:
Aaron B. Waxman, MD, PhD, FACP, FCCP, can be reached at abwaxman@bwh.harvard.edu.