Quantitative HRCT as a surrogate outcome measure for nintedanib treatment in systemic sclerosis-interstitial lung disease and idiopathic pulmonary fibrosis

Objective: We assessed the effect of nintedanib (NIN) in terms of quantitative HRCT changes in both idiopathic pulmonary fibrosis (IPF) and systemic sclerosis-associated progressive interstitial lung disease (SSc-ILD), evaluating the relationships between imaging variations and clinical-functional outcomes. Methods: We prospectively enrolled SSc-ILD and IPF patients treated with NIN and retrospectively selected the same number of subjects from a historical untreated cohort comparable for disease, age, gender and follow-up period. HRCT scans were processed with CALIPER software, obtaining the percentage of normal parenchyma, ILD and vascular-related structures (VRS). Results: Quantitative HRCT changes of 36 NIN treated patients (12 SSc-ILD and 24 IPF) were compared with 36 untreated subjects with pulmonary fibrosis. After a mean follow-up period of 22 months, NIN therapy was associated with a percentage stabilization of normal parenchyma (from 81.3 ±11.8% to 78.6 ±15.6%; p= not significant) and ILD (from 14.5 ±10.4% to 16.7 ±14.2%; p= not significant) both in SSc-ILD and IPF, avoiding the loss of normal parenchyma (from 87.4 ±7.3% to 78.8 ±16.7%; p<0.001) and ILD worsening (from 9.0 ±5.9% to 16.5 ±14.8%; p<0.001) observed in the untreated cohort. VRS was significantly increased regardless of antifibrotic therapy (p<0.001). NIN treated patients who experienced a clinically meaningful worsening at pulmonary function tests or at the reported dyspnoea, presented a significant loss of normal parenchyma in parallel with a greater increase in ILD (p<0.05 for all). Conclusion: NIN appears effective in reducing the radiological decline of pulmonary fibrosis. Quantitative HRCT is proposed as a surrogate outcome measure for clinical practice and future trials.