LAUSR

Introduction: In the INSTAGE trial in subjects with IPF and severely impaired gas exchange, nintedanib plus sildenafil had a numerically greater effect on FVC decline vs nintedanib alone, with more a pronounced effect in subjects with emphysema. Aim: Examine biomarkers of inflammation, cell damage and extracellular matrix (ECM) turnover by presence of emphysema in the INSTAGE trial. Methods: Subjects with IPF and DLco ≤35% predicted were randomised to receive nintedanib 150 mg bid plus sildenafil 20 mg tid or nintedanib 150 mg bid plus placebo. We analysed fold changes from baseline in biomarkers over 24 weeks in subjects with and without emphysema at baseline (determined based on qualitative assessment of an HRCT scan by investigators). Results: In total, 273 subjects were treated. Treatment effects were most notably different between emphysema subgroups for VICM, KL-6 and SP-D. Reductions in VICM (marker of ECM turnover) were observed with nintedanib plus sildenafil vs nintedanib alone only in subjects without emphysema. Reductions in KL-6 and SP-D (markers of epithelial injury) were observed with nintedanib plus sildenafil vs nintedanib alone only in subjects with emphysema. Conclusion: In the INSTAGE trial, nintedanib plus sildenafil reduced markers of epithelial injury vs nintedanib alone in subjects with emphysema and reduced VICM, a marker of ECM turnover, in subjects without emphysema.