Interstitial and diffuse lung disease
Treatment for pulmonary hypertension secondary to interstitial lung disease
The development of pulmonary hypertension (PH) in patients with interstitial lung disease (ILD) (PH-ILD) is associated with increased supplemental oxygen requirements, reduced functional status, and decreased survival (King CS, et al. Chest. 2020;158[4]:1651).
Dr. Adrian Shifren
An inhaled formulation of treprostinil (Tyvaso) is the first treatment option approved by the FDA for patients with PH-ILD, including those with idiopathic pulmonary fibrosis, connective tissue disease-associated ILD, and combined pulmonary fibrosis and emphysema. Approval was based on results from the INCREASE trial (Waxman A, et al. N Engl J Med. 2021;384[4]:325), a phase III multicenter, randomized, double-blinded study comparing the inhaled formulation to placebo in 326 patients over a 16-week period. Participants in the treatment arm were given up to 12 breaths of the formulation per session, four times per day. Subjects treated with this inhaled formulation met the primary study endpoint, an increase in 6-minute walk distance (6MWD) from baseline to week 16, walking 21 m farther than placebo-treated control subjects. Furthermore, patients receiving the new formulation had a decrease in NT-proBNP levels (compared with increases in the placebo arm) and a reduction in clinical worsening (23% of inhalation formulation-treated vs. 33% of placebo-treated subjects). This formulation of treprostinil was well-tolerated with a safety profile consistent with common prostacyclin-related adverse events, including cough, headache, dyspnea, dizziness, nausea, fatigue, and diarrhea. Its approval will dramatically alter the ILD treatment landscape. It now necessitates the use of PH screening in this patient population. However, care will need to be exercised in appropriate patient selection for treatment, using the study inclusion and exclusion criteria as a starting point. Appropriate use of this formulation will hopefully help mitigate the negative outcomes impacting patients with PH-ILD.
Rebecca Anna Gersten, MD
Adrian Shifren, MD
Steering Committee Members