Circulating biomarkers and progression of idiopathic pulmonary fibrosis: data from the INMARK trial
File(s)
Published version
Author(s)
Type
Journal Article
Abstract
BACKGROUND: We used data from the INMARK trial to investigate associations between circulating biomarkers of extracellular matrix (ECM) turnover, inflammation and epithelial dysfunction and disease progression in subjects with idiopathic pulmonary fibrosis (IPF). METHODS: Subjects with IPF and forced vital capacity (FVC) ≥80% predicted were randomised 1:2 to receive nintedanib 150 mg twice daily or placebo for 12 weeks followed by open-label nintedanib for 40 weeks. Associations between baseline biomarker levels and the proportion of subjects with disease progression (decline in FVC ≥10% predicted or death) over 52 weeks were assessed in subjects randomised to placebo using logistic regression. Associations between baseline demographic/clinical characteristics and biomarker levels and disease progression over 52 weeks were analysed using multivariate models. RESULTS: Of 230 subjects who received placebo for 12 weeks then open-label nintedanib for 40 weeks, 70 (30.4%) had disease progression over 52 weeks. Baseline levels of CRPM (C-reactive protein (CRP) degraded by matrix metalloproteinase (MMP)-1/8), C3M (collagen 3 degraded by MMP-9), CRP, KL-6 (Krebs von den Lungen-6) and SP-D (surfactant protein D) were not significantly associated with disease progression over 52 weeks in analyses corrected for multiple comparisons. In models including only baseline demographic/clinical characteristics, 61.2-64.2% of subjects were correctly classified as having or not having disease progression over 52 weeks. When both demographic/clinical characteristics and biomarker levels were included in the models, 50.0-64.5% of the test set were correctly classified. CONCLUSIONS: Among subjects with IPF and preserved FVC, multivariate models based on demographic/clinical characteristics and biomarker levels at baseline did not provide an accurate prediction of which patients would progress.
Date Issued
2024-07
Date Acceptance
2024-03-16
Citation
ERJ Open Research, 2024, 10 (4)
ISSN
2312-0541
Publisher
European Respiratory Society
Journal / Book Title
ERJ Open Research
Volume
10
Issue
4
Copyright Statement
©The authors 2024
This version is distributed under the terms of the Creative Commons Attribution Licence 4.0.
This version is distributed under the terms of the Creative Commons Attribution Licence 4.0.
License URL
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/39040590
Publication Status
Published
Coverage Spatial
England
Article Number
00335-2023
Date Publish Online
2024-07-22