Effects of nintedanib on circulating biomarkers of idiopathic pulmonary fibrosis
Background Biomarkers that change in response to nintedanib in subjects with idiopathic pulmonary fibrosis (IPF) would be valuable. We investigated the effects of nintedanib on circulating biomarkers in subjects with IPF in the INMARK trial. Methods Subjects with IPF were randomised 1:2 to receive n...
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| Format: | Article |
| Language: | English |
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European Respiratory Society
2024-12-01
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| Series: | ERJ Open Research |
| Online Access: | http://openres.ersjournals.com/content/10/6/00558-2023.full |
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| author | R. Gisli Jenkins Vincent Cottin Yasuhiko Nishioka Imre Noth Eric S. White Carina Ittrich Claudia Diefenbach Klaus B. Rohr Moisés Selman Toby M. Maher |
| author_facet | R. Gisli Jenkins Vincent Cottin Yasuhiko Nishioka Imre Noth Eric S. White Carina Ittrich Claudia Diefenbach Klaus B. Rohr Moisés Selman Toby M. Maher |
| author_sort | R. Gisli Jenkins |
| collection | DOAJ |
| description | Background
Biomarkers that change in response to nintedanib in subjects with idiopathic pulmonary fibrosis (IPF) would be valuable. We investigated the effects of nintedanib on circulating biomarkers in subjects with IPF in the INMARK trial.
Methods
Subjects with IPF were randomised 1:2 to receive nintedanib 150 mg twice daily or placebo for 12 weeks, after which all patients received open-label nintedanib for 40 weeks. Fold changes in adjusted mean levels of circulating biomarkers were analysed using a linear mixed model for repeated measures.
Results
346 subjects were treated (116 randomised to nintedanib, 230 to placebo). Surfactant protein D (SP-D) and cancer antigen 125 (CA-125), markers of epithelial injury, decreased in subjects treated with nintedanib versus placebo. Fold changes from baseline in SP-D at week 12 corresponded to a 4% decrease and 3% increase in the nintedanib and placebo groups, respectively (ratio 0.94, 95% CI 0.89–0.99; p=0.024). Fold changes in CA-125 at week 12 corresponded to a 22% decrease and 4% increase in the nintedanib and placebo groups, respectively (ratio 0.75, 95% CI 0.71–0.81; p<0.0001). A mediation analysis suggested that 42.1% of the effect of nintedanib on change in forced vital capacity over 12 weeks was attributable to the change in CA-125. A small increase in C3A (collagen 3 degraded by ADAMTS-1/4/8) and a small decrease in C3M (collagen 3 degraded by matrix metalloproteinase-9), markers of extracellular matrix turnover, were observed in subjects treated with nintedanib versus placebo.
Conclusions
Effects of nintedanib on circulating markers of epithelial dysfunction and collagen degradation, most notably CA-125, were observed in patients with IPF. |
| format | Article |
| id | doaj-art-937e011185334368baf39a76fbab0636 |
| institution | Kabale University |
| issn | 2312-0541 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | European Respiratory Society |
| record_format | Article |
| series | ERJ Open Research |
| spelling | doaj-art-937e011185334368baf39a76fbab06362025-01-14T09:50:22ZengEuropean Respiratory SocietyERJ Open Research2312-05412024-12-0110610.1183/23120541.00558-202300558-2023Effects of nintedanib on circulating biomarkers of idiopathic pulmonary fibrosisR. Gisli Jenkins0Vincent Cottin1Yasuhiko Nishioka2Imre Noth3Eric S. White4Carina Ittrich5Claudia Diefenbach6Klaus B. Rohr7Moisés Selman8Toby M. Maher9 National Heart and Lung Institute, Imperial College London, London, UK National Reference Coordinating Centre for Rare Pulmonary Diseases, Louis Pradel Hospital, Hospices Civils de Lyon, Claude Bernard University Lyon 1, UMR754, Lyon, France Graduate School of Biomedical Sciences, Tokushima University, Tokushima, Japan Division of Pulmonary and Critical Care Medicine, University of Virginia, Charlottesville, VI, USA Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, CT, USA Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach an der Riss, Germany Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach an der Riss, Germany Boehringer Ingelheim International GmbH, Ingelheim am Rhein, Germany Instituto Nacional de Enfermedades Respiratorias “Ismael Cosio Villegas”, Mexico City, Mexico National Heart and Lung Institute, Imperial College London, London, UK Background Biomarkers that change in response to nintedanib in subjects with idiopathic pulmonary fibrosis (IPF) would be valuable. We investigated the effects of nintedanib on circulating biomarkers in subjects with IPF in the INMARK trial. Methods Subjects with IPF were randomised 1:2 to receive nintedanib 150 mg twice daily or placebo for 12 weeks, after which all patients received open-label nintedanib for 40 weeks. Fold changes in adjusted mean levels of circulating biomarkers were analysed using a linear mixed model for repeated measures. Results 346 subjects were treated (116 randomised to nintedanib, 230 to placebo). Surfactant protein D (SP-D) and cancer antigen 125 (CA-125), markers of epithelial injury, decreased in subjects treated with nintedanib versus placebo. Fold changes from baseline in SP-D at week 12 corresponded to a 4% decrease and 3% increase in the nintedanib and placebo groups, respectively (ratio 0.94, 95% CI 0.89–0.99; p=0.024). Fold changes in CA-125 at week 12 corresponded to a 22% decrease and 4% increase in the nintedanib and placebo groups, respectively (ratio 0.75, 95% CI 0.71–0.81; p<0.0001). A mediation analysis suggested that 42.1% of the effect of nintedanib on change in forced vital capacity over 12 weeks was attributable to the change in CA-125. A small increase in C3A (collagen 3 degraded by ADAMTS-1/4/8) and a small decrease in C3M (collagen 3 degraded by matrix metalloproteinase-9), markers of extracellular matrix turnover, were observed in subjects treated with nintedanib versus placebo. Conclusions Effects of nintedanib on circulating markers of epithelial dysfunction and collagen degradation, most notably CA-125, were observed in patients with IPF.http://openres.ersjournals.com/content/10/6/00558-2023.full |
| spellingShingle | R. Gisli Jenkins Vincent Cottin Yasuhiko Nishioka Imre Noth Eric S. White Carina Ittrich Claudia Diefenbach Klaus B. Rohr Moisés Selman Toby M. Maher Effects of nintedanib on circulating biomarkers of idiopathic pulmonary fibrosis ERJ Open Research |
| title | Effects of nintedanib on circulating biomarkers of idiopathic pulmonary fibrosis |
| title_full | Effects of nintedanib on circulating biomarkers of idiopathic pulmonary fibrosis |
| title_fullStr | Effects of nintedanib on circulating biomarkers of idiopathic pulmonary fibrosis |
| title_full_unstemmed | Effects of nintedanib on circulating biomarkers of idiopathic pulmonary fibrosis |
| title_short | Effects of nintedanib on circulating biomarkers of idiopathic pulmonary fibrosis |
| title_sort | effects of nintedanib on circulating biomarkers of idiopathic pulmonary fibrosis |
| url | http://openres.ersjournals.com/content/10/6/00558-2023.full |
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