Abstract
OBJECTIVE: Myositis-associated interstitial lung disease (myositis-ILD) consists of two predominant radiologic patterns of lung injury-nonspecific interstitial pneumonia (NSIP) and organizing pneumonia (OP)-that oftentimes coexist. However, it remains unclear whether either is associated with clinical outcomes. We aimed to assess the therapeutic response in patients with NSIP-compared to those with OP-predominant myositis-ILD. METHODS: This retrospective, single-center cohort study recruited participants from the Northwestern University ILD Registry with a circulating myositis-associated antibody, ILD, and at least 6 months of follow-up while on immunomodulatory therapy during a 24-month observation period after diagnosis. Two thoracic radiologists determined the predominant radiologic pattern (NSIP or OP). The primary outcome was the absolute change in forced vital capacity (FVC) at 24 months post-diagnosis. Secondary outcomes included changes in the diffusing capacity of the lung for carbon monoxide (DLCO) and radiologic qualitative and quantitative measures of lung injury. RESULTS: Forty-one participants were included in analyses. 71% had an OP-predominant while 29% had an NSIP-predominant radiologic pattern of lung injury. Both exposure cohorts had improvement in mean absolute FVC (OP cohort = +0.18L [p=0.005], NSIP cohort = +0.24L [p=0.07]) over the 24-month observation period. The OP (p<0.05) but not the NSIP cohort (p=0.20) had an increase in DLCO. The OP cohort demonstrated improvement in the qualitative assessment of follow-up imaging (p<0.05), driven by quantitative improvement in groundglass/consolidative opacities (p=0.006). A subset of participants demonstrated features of NSIP/OP overlap and had greater baseline radiologic severity of lung injury. CONCLUSION: Patients with circulating myositis-associated antibodies and an OP-predominant pattern of lung injury may have a more favorable response to therapy than those with NSIP. Further studies are needed to validate our findings and delineate other features cognate with these associations. SIGNIFICANCE AND INNOVATIONS: Radiologic phenotyping may predict therapeutic response in myositis-ILD . This study demonstrates that an OP-predominant computed tomography (CT) pattern of lung injury is associated with greater improvement in lung function and radiologic signs of inflammation over 24 months on at least 6 months of immunomodulatory therapy compared with an NSIP-predominant pattern, suggesting that CT pattern may provide clinically meaningful prognostic information. First study to integrate blinded qualitative radiologic adjudication with quantitative CT scoring in myositis-ILD . By combining dual-radiologist review with Kazerooni quantitative scoring and longitudinal pulmonary function testing, this study offers a rigorous and multidimensional assessment of treatment response. Expands risk stratification beyond antibody-based toward imaging-based phenotyping strategies . In a heterogeneous population defined by diverse myositis-associated antibodies, this work introduces radiologic pattern as a practical and accessible framework for anticipating treatment responsiveness. Provides hypothesis-generating data for precision management in myositis-ILD . The findings support the concept that imaging-defined subgroups may exhibit differential therapeutic trajectories, laying groundwork for future multicenter studies integrating CT phenotype, antibody profile, and treatment strategy.