Abstract

A proportion of patients with fibrosing interstitial lung diseases (ILDs) develop a progressive phenotype characterised by decline in lung function, worsening quality of life and early mortality. Other than idiopathic pulmonary fibrosis (IPF), there are no approved drugs for fibrosing ILDs and a poor evidence base to support current treatments. Fibrosing ILDs with a progressive phenotype show commonalities in clinical behaviour and in the pathogenic mechanisms that drive disease worsening. Nintedanib is an intracellular inhibitor of tyrosine kinases that has been approved for treatment of IPF and has recently been shown to reduce the rate of lung function decline in patients with ILD associated with systemic sclerosis (SSc-ILD). In vitro data demonstrate that nintedanib inhibits several steps in the initiation and progression of lung fibrosis, including the release of pro-inflammatory and pro-fibrotic mediators, migration and differentiation of fibrocytes and fibroblasts, and deposition of extracellular matrix. Nintedanib also inhibits the proliferation of vascular cells. Studies in animal models with features of fibrosing ILDs such as IPF, SSc-ILD, rheumatoid arthritis-ILD, hypersensitivity pneumonitis and silicosis demonstrate that nintedanib has anti-fibrotic activity irrespective of the trigger for the lung pathology. This suggests that nintedanib inhibits fundamental processes in the pathogenesis of fibrosis. A trial of nintedanib in patients with progressive fibrosing ILDs other than IPF (INBUILD) will report results in 2019.

Footnotes

This manuscript has recently been accepted for publication in the European Respiratory Journal. It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article.

Conflict of interest: Lutz Wollin is an employee of Boehringer Ingelheim Pharma GmbH & Co KG

Conflict of interest: Dr. Distler has nothing to disclose.

Conflict of interest: Dr. Redente has nothing to disclose.

Conflict of interest: Dr. Riches has nothing to disclose.

Conflict of interest: Susanne Stowasser is an employee of Boehringer Ingelheim International GmbH

Conflict of interest: Rozsa Schlenker-Herceg is an employee of Boehringer Ingelheim Pharmaceuticals, Inc.

Conflict of interest: Toby M Maher has, via his institution, received industry-academic funding from GlaxoSmithKline R&D and UCB; has received consultancy or speakers fees from Apellis, AstraZeneca, Bayer, Biogen Idec, Boehringer Ingelheim, Galapagos, GlaxoSmithKline R&D, Indalo, Pliant, ProMetic, Roche, Samumed and UCB; and has received consultancy fees from Galecto.

Conflict of interest: Dr. Kolb reports grants and personal fees from Roche, grants and personal fees from Boehringer Ingelheim , grants and personal fees from GSK, grants and personal fees from Gilead, grants from Actelion, grants from Respivert, personal fees from Genoa, grants from Alkermes, grants from Pharmaxis, grants and personal fees from Prometic, personal fees from Indalo, personal fees from Third Pole, outside the submitted work.