Long-term inhaled treprostinil for pulmonary hypertension due to interstitial lung disease: INCREASE open-label extension study.

INTRODUCTION: The 16-week randomised, placebo-controlled INCREASE trial (RCT) met its primary end-point by improving 6-min walk distance (6MWD) in patients receiving inhaled treprostinil for pulmonary hypertension due to interstitial lung disease (PH-ILD). The open-label extension (OLE) evaluated long-term effects of inhaled treprostinil in PH-ILD. METHODS: Of 258 eligible patients, 242 enrolled in the INCREASE OLE and received inhaled treprostinil. Assessments included 6MWD, pulmonary function testing, N-terminal pro-brain natriuretic peptide (NT-proBNP), quality of life and adverse events. Hospitalisations, exacerbations of underlying lung disease and death were recorded. RESULTS: At INCREASE OLE baseline, patients had a median age of 70 years and a mean 6MWD of 274.2 m; 52.1% were male. For the overall population, the mean 6MWD at week 52 was 279.1 m and the mean change from INCREASE RCT baseline was 3.5 m (22.1 m for the prior inhaled treprostinil arm and -19.5 m for the prior placebo arm); the median NT-proBNP decreased from 389 pg·mL-1 at RCT baseline to 359 pg·mL-1 at week 64; and the absolute (% predicted) mean forced vital capacity change from RCT baseline to week 64 was 51 mL (2.8%). Patients who received inhaled treprostinil versus placebo in the RCT had a 31% lower relative risk of exacerbation of underlying lung disease in the OLE (hazard ratio 0.69 (95% CI 0.49-0.97); p=0.03). Adverse events leading to drug discontinuation occurred in 54 (22.3%) patients. CONCLUSIONS: These results support the long-term safety and efficacy of inhaled treprostinil in patients with PH-ILD, and are consistent with the results observed in the INCREASE RCT.

Clinical use of nintedanib in patients with idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a rare lung disease characterised by progressive loss of lung function, dyspnoea and cough. IPF has a variable clinical course but a poor prognosis. Nintedanib, a tyrosine kinase inhibitor, is one of two drugs approved for the treatment of IPF. In clinical trials, nintedanib slowed disease progression by reducing the rate of decline in forced vital capacity (FVC) in patients with IPF and mild or moderate lung function impairment. The effect of nintedanib was consistent across patient subgroups defined by baseline characteristics including FVC % predicted, diffusion capacity of the lung for carbon monoxide % predicted and the presence of emphysema. Recently, it has been shown that the rate of decline in FVC and the treatment effect of nintedanib are the same in patients with preserved lung volume (FVC >90% predicted) as in patients with greater impairment in FVC, supporting the value of early treatment of IPF. The adverse events most commonly associated with nintedanib, both in clinical trials and real-world clinical practice, are mild gastrointestinal events, particularly diarrhoea. Side effects are manageable in a majority of patients through symptomatic treatment, dose reductions and treatment interruptions, enabling most patients to stay on treatment in the long term.