C104-12 Temporality of Disease Onset and Clinical Outcomes in Systemic Autoimmune Rheumatic Disease-Associated Interstitial Lung Disease

Abstract Rationale Interstitial lung disease (ILD) is one of the most common systemic complications in myositis, the number one cause of death in systemic sclerosis, and the number two cause of death in rheumatoid arthritis.1 ILD may precede, follow, or coincide with the diagnosis of a systemic autoimmune rheumatic disease (SARD), but the prognostic implications of this timing remain unclear. We aimed to determine whether the timing of ILD diagnosis in patients with SARD influences pulmonary progression-free survival (PFS) and mortality. Methods We conducted a retrospective cohort study using data from an institutional ILD registry at Beth Israel Deaconess Medical Center which included 109 patients with SARD-ILD. Patients were categorized based on the timing of diagnosis as ILD-first, SARD-first, or concurrent. The primary outcome was PFS, defined as ≥ 10% relative forced vital capacity (FVC) decline, respiratory hospitalization, transplant, or death. Kaplan-Meier curves with log-rank analyses and a multivariable Cox proportional-hazards model that adjusted for age, sex, pulmonary hypertension, baseline FVC, smoking status, and ever immunosuppressant or antifibrotic use compared PFS across categories (Figure 1). Results Among 109 patients (mean age 67 ± 15 years; 79% female), the baseline mean FVC was 75% ± 22% predicted and DLCO was 63% ± 23%. SARD subtypes included systemic sclerosis (26%), rheumatoid arthritis (12%), idiopathic inflammatory myopathy (15%), mixed connective tissue disease (21%), and others. 58 patients (53%) were diagnosed SARD-first, 20 (18%) ILD-first, and 31(28%) concurrently. Over follow-up, 39 patients (36%) met the composite endpoint. Kaplan-Meier analysis showed no significant difference in progression-free survival (PFS) between SARD-first and ILD-first patients (log-rank p = 0.34; Figure 1). In the adjusted Cox model, SARD-first presentation was associated with a higher risk of progression versus ILD-first (HR 4.69, 95%CI 1.10-20.09). Concurrent diagnosis compared to ILD-first showed a non-significant trend toward increased risk (HR 2.53, 95%CI 0.59-10.86). Conclusions The timing of ILD diagnosis in SARD may influence clinical trajectory. Contrary to our initial hypothesis, patients with established SARD prior to development of ILD demonstrated a trend toward shorter pulmonary progression-free survival. This finding may reflect a difference in underlying disease phenotype or cumulative treatment exposure and highlights the need for larger multicenter analyses to further clarify the prognostic role of diagnostic temporality in SARD-ILD. References: 1.Kawano-Dourado L, Lee JS. Management of Connective Tissue Disease-Associated Interstitial Lung Disease. Clin Chest Med. 2021;42(2):295-310. doi:10.1016/j.ccm.2021.03.010 Figure 1. Kaplan-Meier curves for ILD progression-free survival stratified by timing of SARD and ILD diagnosis. This abstract is funded by: None