Long-term effects of inhaled treprostinil in Japanese patients with pulmonary hypertension associated with interstitial lung disease.

BACKGROUND

Treprostinil has been approved for pulmonary hypertension associated with interstitial lung disease (PH-ILD) in Japan. This report aimed to evaluate long-term effects of inhaled treprostinil in Japanese patients with PH-ILD based on observation over 52 weeks.

METHODS

Inhaled treprostinil was administered via a nebulizer from 18 μg (three breaths, four times daily) to 72 μg (12 breaths, four times daily) at minimum 3-day intervals. World Health Organization (WHO) functional class, clinical worsening, adverse events, pulmonary function and ILD-related biomarkers were evaluated throughout the trial.

RESULTS

Among 20 patients, 16 and 13 completed the 52-week and 100-week observation periods, respectively. Eleven patients continued on the trial until transitioning to a commercially available product. The reasons of discontinuation in nine patients were adverse events in six patients (including four adverse drug reactions (ADRs)), withdrawal of consent in two patients, and lung transplantation in one patient. The median observation period was 107.5 weeks (interquartile range, 61.4-128.8 weeks) in 20 patients. Among 13 patients observed until week 100, WHO functional class was maintained in 69.2 % (9/13), and improved from class III to class II in 30.8 % (4/13). The main ADRs included cough, malaise, and blood pressure decreased. At the final measurement timepoint in each patient, 70.0 % (14/20) and 83.3 % (15/18) maintained had no absolute decline of forced vital capacity ≥5 % and diffusing capacity for carbon monoxide ≥10 %, respectively.

CONCLUSION

Considering its long-term clinical benefits and tolerability, inhaled treprostinil is a promising treatment option for patients with PH-ILD.

TRIAL REGISTRATION: Japan Registry of Clinical Trials (jRCT), jRCT2051210016. (first registered: May 7, 2021).