Nintedanib in Progressive Fibrosing Interstitial Lung Diseases
Open accessAbstract
BACKGROUND: Preclinical data have suggested that nintedanib, an intracellular inhibitor of tyrosine kinases, inhibits processes involved in the progression of lung fibrosis. Although the efficacy of nintedanib has been shown in idiopathic pulmonary fibrosis, its efficacy across a broad range of fibrosing lung diseases is unknown. METHODS: In this double-blind, placebo-controlled, phase 3 trial conducted in 15 countries, we randomly assigned patients with fibrosing lung disease affecting more than 10% of lung volume on high-resolution computed tomography (CT) to receive nintedanib at a dose of 150 mg twice daily or placebo. All the patients met criteria for progression of interstitial lung disease in the past 24 months despite treatment and had a forced vital capacity (FVC) of at least 45% of the predicted value and a diffusing capacity of the lung for carbon monoxide ranging from 30 to less than 80% of the predicted value. Randomization was stratified according to the fibrotic pattern (a pattern of usual interstitial pneumonia [UIP] or other fibrotic patterns) on high-resolution CT. The primary end point was the annual rate of decline in the FVC, as assessed over a 52-week period. The two primary populations for analysis were the overall population and patients with a UIP-like fibrotic pattern. RESULTS: A total of 663 patients were treated. In the overall population, the adjusted rate of decline in the FVC was -80.8 ml per year with nintedanib and -187.8 ml per year with placebo, for a between-group difference of 107.0 ml per year (95% confidence interval [CI], 65.4 to 148.5; P<0.001). In patients with a UIP-like fibrotic pattern, the adjusted rate of decline in the FVC was -82.9 ml per year with nintedanib and -211.1 ml per year with placebo, for a difference of 128.2 ml (95% CI, 70.8 to 185.6; P<0.001). Diarrhea was the most common adverse event, as reported in 66.9% and 23.9% of patients treated with nintedanib and placebo, respectively. Abnormalities on liver-function testing were more common in the nintedanib group than in the placebo group. CONCLUSIONS: 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. (Funded by Boehringer Ingelheim; INBUILD ClinicalTrials.gov number, NCT02999178.).
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The observed survival difference in favour of antifibrotic therapy is in accordance with recent clinical trials showing that antifibrotic therapies are effective in progressive fibrotic interstitial lung diseases other than IPF.
“This observation is therefore in accordance with recent clinical trials showing that antifibrotic therapies are effective in progressive fibrotic interstitial lung diseases other than IPF [20,26,27].”
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- resulted in death, was life-threatening, resulted in hospitalization or prolongation of hospitalization, resulted in persistent or clinically significant disability or incapacity, was a congenital anomaly or birth defect, or was deemed to be serious for any other reason. ILD denotes interstitial lung disease. P19-08802 New England Journal of Medicine 2019 _______________________________________________________________________________________________________________
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- Authors
- Flaherty, K. R., Wells, A. U., Cottin, V., Devaraj, A., Walsh, S. L. F., Inoue, Y., Richeldi, L., Kolb, M., Tetzlaff, K., Stowasser, S., Coeck, C., Clerisme-Beaty, E., Rosenstock, B., Quaresma, M., Haeufel, T., Goeldner, R.-G., Schlenker-Herceg, R., & Brown, K. K.
- Affiliations
- University of Michigan (US)
- Lyon 1 Université (FR)
- Università Cattolica del Sacro Cuore (IT)
- Boehringer Ingelheim (Germany) (DE)
- From the Division of Pulmonary and Critical Care Medicine, University of Michigan, Ann Arbor (K.R.F.); the National Institute for Health Research Respiratory Biomedical Research Unit, Royal Brompton and Harefield NHS Foundation Trust (A.U.W.), the National Heart and Lung Institute, Imperial College (A.U.W., A.D., S.L.F.W.), and the Department of Radiology, Royal Brompton and Harefield NHS Foundation Trust (A.D.) — all in London; the National Reference Center for Rare Pulmonary Diseases, Louis Pradel...
- ORCID
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2019-10-31
- Volume
- 381
- Issue
- 18
- Pages
- 1718-1727
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- OpenAlex
- W2974960379
- Cited by
- 2,403
- References
- 26
- Citations by year
- 2026: 263 · 2025: 350 · 2024: 380 · 2023: 396 · 2022: 377 · 2021: 381 · 2020: 230 · 2019: 20 · 2018: 1 · 2016: 1 · 2014: 1 · 2012: 1
- FWCI
- 185.31
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- Dépôt institutionnel de l'Université libre de Bruxelles (Université Libre de Bruxelles) (submittedVersion, other-oa)
- Digital Access to Libraries (submittedVersion, other-oa)
- Florence Research (University of Florence) (submittedVersion)
- Research Explorer (The University of Manchester) (submittedVersion, other-oa)
- Seoul National University Open Repository (Seoul National University) (submittedVersion)
- Funders
- Boehringer Ingelheim
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Health Sciences › Medicine › Pathology and Forensic Medicine › Systemic Sclerosis and Related Diseases
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Pulmonary Hypertension Research and Treatments
- Keywords
- nintedanib, fibrotic interstitial lung disease, usual interstitial pneumonia, forced vital capacity decline, tyrosine kinase inhibitors, lung fibrosis progression, antifibrotic therapy, diarrhea, liver dysfunction, idiopathic pulmonary fibrosis, diffusing capacity for carbon monoxide, adverse events, drug safety and efficacy comparison
- MeSH terms
- Aged, Diarrhea, Double-Blind Method, Female, Humans, Indoles, Male, Middle Aged, Vital Capacity, Disease Progression, Protein Kinase Inhibitors, Idiopathic Pulmonary Fibrosis
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