Interstitial lung disease · Antifibrotics beyond IPF
Nintedanib in Progressive Fibrosing Interstitial Lung Diseases
| Design | Double-blind, placebo-controlled, phase 3 trial in 15 countries |
|---|---|
| Treatment | Nintedanib 150 mg twice daily |
| Control | Placebo |
| Population | 663 patients with fibrosing lung disease affecting more than 10% of lung volume on HRCT and progression in the past 24 months despite treatment |
| Inclusion criteria | FVC at least 45% predicted, DLCO 30% to less than 80% predicted, with progression of interstitial lung disease in the previous 24 months despite treatment. Randomisation stratified by UIP-like or other fibrotic pattern. |
| Follow-up | 52 weeks |
| Primary endpoint | Annual rate of decline in FVC |
| Result | FVC decline -80.8 mL/year with nintedanib versus -187.8 mL/year with placebo — difference 107.0 mL/year (95% CI 65.4 to 148.5, p<0.001). In the UIP-like subgroup, -82.9 versus -211.1 mL/year (difference 128.2 mL, 70.8 to 185.6, p<0.001). Diarrhoea affected 66.9% versus 23.9%, with more liver function abnormalities on nintedanib. |
| Secondary endpoints | FVC decline by fibrotic pattern, quality of life, acute exacerbation, death |
In patients with progressive fibrosing interstitial lung diseases, the annual rate of decline in the FVC was significantly lower among patients who received nintedanib than among those who received placebo. Diarrhea was a common adverse event.
The trial authors, in the published abstract
Reframed the field: it enrolled by behaviour — fibrosis that is progressing — rather than by diagnosis, and found that antifibrotics work anyway. Progressive pulmonary fibrosis became a treatable entity in its own right, and FIBRONEER-ILD has since followed the same design.
Flaherty KR, Wells AU, Cottin V, et al. Nintedanib in Progressive Fibrosing Interstitial Lung Diseases. N Engl J Med 2019 Oct 31;381(18):1718-1727.