Effect of nintedanib on blood biomarkers in patients with IPF in the INMARK trial

Abstract

Introduction: The INMARK trial investigated blood biomarkers as predictors of disease progression in subjects with IPF and the effect of nintedanib on changes in these biomarkers. Aim: To investigate the effect of nintedanib on changes in biomarkers of extracellular matrix turnover, inflammation and epithelial dysfunction. Methods: Subjects with IPF and FVC ≥80% predicted were randomised 1:2 to receive nintedanib 150 mg bid or placebo for 12 weeks. Absolute changes from baseline in biomarkers at weeks 4 and 12 with nintedanib vs placebo were analysed using a mixed model for repeated measures. Results: A total of 346 subjects (116 randomised to nintedanib, 230 to placebo) were treated. At baseline, mean (SD) FVC was 97.5 (13.5) % predicted. Compared with placebo, nintedanib significantly reduced levels of N-terminal propeptide of type VI collagen (Pro-C6) and surfactant protein D (SP-D), while CRP levels were significantly increased, at weeks 4 and 12 (Table). Levels of these three biomarkers were stable in the placebo group. Pro-C3 levels were significantly increased with nintedanib versus placebo at week 4 but not at week 12. Conclusions: These results suggest that nintedanib may reduce collagen synthesis, as measured by Pro-C6, and epithelial injury, as measured by SP-D, in patients with IPF and limited FVC impairment. Changes in these biomarkers were observed as early as week 4.