Impact of quantitative radiological features of interstitial lung disease on immunomodulatory treatment response in three autoimmune interstitial lung disease cohorts

BACKGROUND: The defining radiological features of autoimmune interstitial lung disease (ILD) are ground glass opacification (GGO) and fibrosis. The associations between these features and physiological response to immunomodulation remain unclear. METHODS: This study leveraged three autoimmune ILD cohorts: two with systemic sclerosis (SSc) and one with rheumatoid arthritis (RA) which were selected for inherent differences in fibrotic extents/patterns. Linear regression models examined associations between baseline quantitative GGO, fibrosis, their ratio and forced vital capacity (FVC)%-predicted changes after 12 months of immunomodulatory therapy. RESULTS: Patients with SSc-ILD (N=262) exhibited a higher GGO-to-fibrosis ratio compared with patients with RA-ILD (N=130) (mean ratio 3.0 vs 0.25). Increased GGO-to-fibrosis was not associated with improved FVC%-predicted in any cohort. Conversely, in patients with SSc-ILD treated with cyclophosphamide (CYC), increased fibrosis (estimate 0.17 (95% CI 0.003, 0.33); p=0.04) and increased GGO (estimate 0.15 (95% CI 0.004, 0.30); p=0.044) were both significantly associated with FVC% improvement. Given the negative direction of the estimate for GGO-to-fibrosis ratio (estimate -0.33 (95% CI -0.61, -0.06); p=0.016), CYC was associated with greater FVC% improvement in patients with a higher degree of fibrosis relative to GGO. No significant correlation was seen in patients with SSc-ILD treated with mycophenolate (N=56) or in patients with RA-ILD treated with immunomodulation (N=130). DISCUSSION: Increased quantitative GGO relative to fibrosis was not significantly associated with improved response to immunomodulation in patients with RA-ILD and SSc-ILD. However, increased quantitative fibrosis and GGO extent were associated with improved response to CYC in SSc-ILD. More research is needed to understand how to use radiological features to guide treatment selection in ILD.