Blood biomarkers predicting disease progression in patients with IPF: data from the INMARK trial

Abstract

Introduction: The INMARK trial investigated biomarkers as predictors of disease progression in patients with IPF and preserved lung volume. Aim: To assess the association between baseline values of biomarkers of extracellular matrix turnover, inflammation and epithelial dysfunction and disease progression in the INMARK trial. Methods: Subjects with IPF and FVC ≥80% predicted were randomised 1:2 to receive nintedanib 150 mg bid or placebo for 12 weeks followed by open-label nintedanib for 40 weeks. The association between baseline levels of biomarkers and the proportion of subjects with disease progression (absolute decline in FVC ≥10% predicted or death) over 52 weeks was assessed in the placebo group using a logistic regression analysis with the baseline value of the biomarker as a linear covariate. Results: A total of 230 subjects (mean [SD] baseline FVC 98.0 [12.6]% predicted) received placebo for 12 weeks followed by open-label nintedanib for 40 weeks, of whom 70 (30.4%) had disease progression over 52 weeks. Baseline C-reactive protein degraded by MMP-1/8 (CRPM), collagen 3 degraded by MMP-9 (C3M), C-reactive protein (CRP), Krebs von den Lungen-6 (KL-6) and surfactant protein D (SP-D) were significantly associated with disease progression over 52 weeks (Table). Conclusions: Levels of CRPM, C3M, CRP, KL-6 and SP-D may be predictors of disease progression in patients with IPF and limited FVC impairment.