POS0425 SUBCLINICAL LOSS OF LUNG VOLUMES IN VERY EARLY SSc: EVIDENCE FROM THE VEDOSS DATABASE
Authors: V. Kakkar, S. DI Donato, R. Ross, C. W. Wasson, S. Bellando-Randone, M. Matucci-Cerinic, Y. Allanore, F. Del Galdo
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> Systemic sclerosis (SSc) is a heterogenous chronic autoimmune disease in which lung fibrosis remains the major driver of mortality. Data from the literature indicate that at the time of diagnosis of SSc-ILD and/or inclusion in clinical intervention studies the mean Forced Vital Capacity (FVC) ranges from 66.5% to 72.6[1]. This suggests that there is a preclinical phase of SSc-ILD where a loss in lung volumes is not detected either by patients or current diagnostic methods. The VEDOSS project has demonstrated that more than 50% of patients with Raynaud's and at least one "red flag" sign progress to fulfil ACR classification criteria within 5 years[2]. This data and other independent studies do support the notion of a subclinical involvement very early within the natural history of SSc and a relative window of opportunity for preventive intervention. In this context, the natural history of lung function has never been investigated in patient meeting the VEDOSS criteria. <h3>Objectives:</h3> Here we aimed to analyse the trajectory of FVC over time in the VEDOSS population and Determine the presence and prevalence of subclinical lung volume loss in this population. <h3>Methods:</h3> Patients in the VEDOSS database were analysed according to the EULAR CP140. Data were screened for patients with available FVC at baseline and at least one follow-up. Patients fulfilling ACR/EULAR criteria at baseline were excluded. Lung function progress was assessed adapting the suggested progressive-fibrosis ILD (PF-ILD) definition as per George et al[3], even in the absence of ILD diagnosis. Specifically, VEDOSS patients were considered to have a subclinical lung volume loss if they showed either a relative FVC decline of 10% or a 5% decline in FVC and a 15% decline in DLCO during follow-up. Progression to fulfil ACR-EULAR 2013 was also considered in the analysis. (Statistical methods Wilcoxon rank sum test, Fisher's exact test, and Pearson's Chi-square test were employed as appropriate - RStudio Version 2023.12.0 + 369). <h3>Results:</h3> 1200 patients recruited from January 2010 to November 2021 were available for analysis. 591 patients were excluded as they met ACR/EULAR classification criteria at baseline or did not have at least 1 follow-up visit. 378 had available PFT at baseline and at least one follow-up. Baseline FVC was 106% (median, [IQR 95, 116]) and median FVC at last available follow up was 107% (IQR 95, 119). Baseline DLCO was 85% (median, [IQR 75, 96]) and median DLCO at last available follow up was 83% (IQR 73, 93). 65 patients (17.2%) met the adapted PF-ILD criteria with a median baseline FVC of 112% (IQR 103, 121) and a median follow-up FVC of 95% (IQR 86, 104) (Table 1). Their median baseline DLCO was 85% (IQR 72, 96) and a median follow-up DLCO of 78% (IQR 66, 91) (Table 1). This group were defined as subclinical progressors. 32 (49%) subclinical progressors also met the ACR/EULAR criteria vs 91/313 of the non-progressors (29%) (P = 0.02). Figure 1 shows the Kaplan-Meier estimates of cumulative event probability (meeting the adapted PF-ILD criteria) in the whole cohort and according to patient who met or did not meet the ACR/EULAR 2013 criteria during follow up. <h3>Conclusion:</h3> Data from the EUSTAR database demonstrated evidence of subclinical lung volume loss in the VEDOSS population. Only half of the subclinical progressors met ACR 2013 criteria during follow up suggesting un unmet need in very early detection of lung involvement in SSc. Further prospective research is warranted to identify the relation between subclinical volume loss and future development of ILD to inform preventive approaches in the very early population. <h3>REFERENCES:</h3> [1] Distler O et al. Nintedanib for Systemic Sclerosis-Associated ILD. N Engl J Med. 2019;380(26):2518-28. [2] Silvia Bellando-Randone P et al. Progression of patients with Raynaud's phenomenon to SSc: a five-year analysis of the European SSc Trial and Research group multicentre, longitudinal registry study for VEDOSS. The Lancet Rheum. 2021;3:e834-43. [3] George PM et al. Progressive fibrosing ILD: clinical uncertainties, consensus recommendations, and research priorities. Lancet Respir Med. 2020;8(9):925-34. <b>Table 1.</b> <h3>Acknowledgements:</h3> EUSTAR Very Early Diagnosis of Systemic Sclerosis collaborators. <h3>Disclosure of Interests:</h3> Vishal Kakkar: None declared, Stefano Di Donato: None declared, Rebecca Ross: None declared, Christopher W Wasson: None declared, Silvia Bellando-Randone: None declared, Marco Matucci-Cerinic: None declared, Yannick Allanore: None declared, Francesco Del Galdo Research support and fees from Abbvie.