Patients with pulmonary hypertension (PH) caused by interstitial lung disease (ILD) experienced greater improvements in exercise capacity with inhaled treprostinil compared with placebo, according to findings from the INCREASE study (ClinicalTrials.gov Identifier: NCT02630316) published in the New England Journal of Medicine.
Investigators of the multicenter INCREASE trial randomly assigned 326 patients with ILD and PH to treatment with either inhaled treprostinil (n=163) or placebo (n=163) for 16 weeks. Treprostinil was administered via an ultrasonic, pulsed-delivery nebulizer and delivered in up to 12 breaths 4 times per day. Overall, patients in this treatment group took a median of 11 breaths (66 μg) by week 12 and 12 breaths (72 μg) per session by week 16.
Researchers compared the 2 groups in terms of changes in peak 6-minute walk distance (6MWD) from baseline to week 16. Secondary endpoints of the study included the changes in N-terminal pro-B-type natriuretic peptide (NT-proBNP) level from baseline to week 16 and time to clinical worsening.
The change in peak 6MWD from baseline to week 16 was significantly greater in the inhaled treprostinil group (21.08±5.12 vs -10.04±5.12 m; treatment effect, 31.12±7.25 m; 95% CI, 16.85-45.39; P <.001). The researchers also observed a 15% reduction in NT-proBNP levels from baseline in patients treated with inhaled treprostinil vs an increase of 46% in the placebo group (treatment ratio, 0.58; 95% CI, 0.47-0.72; P <.001).
More participants in the placebo group experienced clinical worsening compared with those in the treprostinil group (33.1% vs 22.7%, respectively; hazard ratio, 0.61; 95% CI, 0.40-0.92; P =.04). Significantly fewer patients in the treprostinil group experienced exacerbations of underlying lung disease compared with those in the placebo group (26.4% vs 38.7%; P =.02).
There was no difference between the 2 groups in terms of the incidence of serious adverse events (AEs). The most common AEs reported in the overall population included cough, headache, dyspnea, dizziness, nausea, fatigue, and diarrhea.
Limitations of this trial included its short duration, the relatively high rate of participant discontinuation from the trial (21%), and the lack of adjudication of events of clinical worsening by an independent review committee.
Disclosure: This clinical trial was supported by United Therapeutics. Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.
Waxman A, Restrepo-Jaramillo R, Thenappan T, et al. Inhaled treprostinil in pulmonary hypertension due to interstitial lung disease. Published online January 13, 2021. N Engl J Med. doi:10.1056/NEJMoa2008470