Association between Functional Improvement and Structural Changes in Quantitative High-resolution CT in ATLAS: a Phase 1b Study of Inhaled Pirfenidone in Idiopathic Pulmonary Fibrosis

<bold>Introduction:</bold> Functional Improvement (FI) is conventionally measured by FVC changes. FI is not commonly observed in subjects with idiopathic pulmonary fibrosis (IPF). While FI may indicate response to medication, its correlation with structural change has been underexplored. <bold>Aims:</bold> This study aimed to associate the FVC changes with quantitative high-resolution CT (HRCT) changes in a cohort of 91 subjects with IPF enrolled in the phase 1b AP01-002 clinical trial (ATLAS) of aerosolized pirfenidone. <bold>Methods:</bold> Among 91 participants, 84 had at least one monthly FVC follow up. In 70 subjects who underwent baseline and 24-week HRCT scans, 68 had both acceptable HRCT in image quality and available FVC scores. FI was defined by any positive changes in the percent predicted FVC (ppFVC) for 24 weeks. Quantitative lung fibrosis (QLF) was obtained from HRCT using machine learning technique. Summary statistics and associations were reported to assess the relationship between ppFVC and HRCT changes. <bold>Results:</bold> The distribution of FI in participants was 63.1% (N=53/84, ppFVC 95% CI (3.36, 5.70%)). With available HRCT, FI was 67.6% (N=46/68) and non-FI (stable/worsening) was 32.4% (N=22/68). Means (95% CI) QLF changes were -0.28% (−1.13, 1.68) for FI group, and 2.44% (−0.11, 5.00) for stable/worsening group. QLF changes from HRCT was significantly associated with ppFVC changes at week 24 (rho=-0.34, p=0.0177). <bold>Conclusions:</bold> FI was frequently observed in 67.6% at week 24. Both functional and structural changes were associated over a 24-week course of therapy.