Pos0831 Predictive Significance of Biomarkers in Systemic Sclerosis-Associated Interstitial Lung Disease: Insights Into Progression, Lung Volume Changes, and Mortality Risk

Background: Interstitial lung disease (ILD) is a leading cause of mortality in scleroderma, underscoring the critical demand for reliable biomarkers. KL-6 and IL-18, have been investigated as potential lung-specific biomarkers in different types of ILD, including systemic sclerosis (SSc) however, their predictive significance for ILD progression and associations with mortality remains unclear. Objectives: Our study aimed to assess the predictive significance of KL-6 and IL-18 for ILD progression and short-term lung volume changes, and also to explore their potential associations with mortality. Methods: We conducted a prospective and longitudinal investigation, including patients diagnosed with systemic sclerosis based on the 2013 ACR/EULAR criteria. Classification was based on the presence of interstitial lung disease (ILD). Baseline and follow-up measurements at 12-18 months of chest high-resolution computed tomography (HRCT) scans and pulmonary function tests were retrieved. The annualized rate of change in forced vital capacity (FVC%) from baseline to follow-up served as a surrogate outcome for ILD progression. Serum concentrations of KL-6 and IL-18 were quantified using established quantitative ELISA techniques. We examined the sensitivity and specificity of various cut-off values of serum KL-6, IL-18, %DLCO, and %FVC annualized change for predicting survival. Results: In our investigation of 74 SSc patients (38% with ILD) with a mean disease duration of 8±8 years, 7 patients (9.5%) died during follow-up. FVC% change ranged from −28% to 24%, and DLCO% change ranged from -38% to 28%. Higher KL-6 levels at baseline were predictive of faster %FVC decline (β=-0.34, p=0.006) and %DLCO (β=-0.24, p=0.04) at 1-year follow-up (Figure 1). Higher IL-18 levels at baseline were predictive of faster %FVC decline (β=-0.24, p=0.04) but not %DLCO decline. Moreover, KL-6 and IL-18 remained independent predictors after adjustment for sex, skin involvement, anti-Scl-70 positivity, smoking, and immunosuppressive treatment status in multivariable models. A significant correlation between mortality and KL-6 (β=0.32, p=0.003), %DLCO (β=0.57, p=0.003), and %FVC (β=0.62, p=0.002) was found. %DLCO showed the best performance in predicting mortality compared to the other biomarkers. ROC analysis showed 368.34 U/mL as the KL-6 serum concentration for predicting mortality in SSc patients (Figure 2). Conclusion: Our study highlights KL-6 and IL-18 as robust predictors of ILD progression in SSc, with independent associations with short-term lung volume changes. These findings suggest their potential clinical relevance for assessing disease dynamics and guiding personalized treatment approaches. Notably, %DLCO emerges as a superior predictor of mortality compared to KL-6 and IL-18, offering a valuable tool for risk stratification in SSc patients. These results contribute to advancing our understanding of SSc-ILD pathogenesis and underscore the need for ongoing research to enhance prognostic accuracy and refine therapeutic strategies.REFERENCES: NIL. Acknowledgements: NIL. Disclosure of Interests: None declared.