POS1242 PREDICTORS AND PATTERN OF DAMAGE AT 15-YEAR FOLLOW-UP IN AN ITALIAN MULTI-CENTER PRIMARY SJÖGREN’S SYNDROME COHORT: A HIERARCHICAL CLUSTERING ANALYSIS
Authors: E. Bartoloni, G. Cafaro, F. Ferro, R. Dal Pozzolo, B. Dei, L. Bruno, I. C. Navarro García, C. Perricone, M. Mosca, R. Gerli, C. Baldini
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> Primary Sjögren's syndrome (pSS) is characterized by a highly heterogeneous phenotype driven by different clinical manifestations and by an unpredictable course. Moreover, up to 15% of patients may develop systemic manifestations and about 45% accumulate permanent damage after 5-10 years of disease. However, no study evaluated damage at longer follow-up nor analysed disease phenotypes which, at baseline, may identify patient clusters at higher risk to accrue irreversible damage. <h3>Objectives:</h3> To evaluate features and factors associated with damage accrual and to identify disease-related variables and phenotypes at higher risk to develop damage at 15 years. <h3>Methods:</h3> A cohort of pSS patients fulfilling the 2002 AECG and/or 2016 ACR/EULAR classification criteria and with at least 15 years of regular follow-up (no gaps longer than 18 months between two visits) was retrospectively included. Demographic, clinical and serological parameters, disease activity by ESSDAI, Charlson Comorbidity Index, disease damage by SSDDI and treatments were recorded every 5 years from diagnosis to 15-year follow-up. Changes of continuous and polytomous variables among timepoints was evaluated by Friedman's test. Dichotomous variables were compared among timepoints by Cochran Q test, followed by pairwise analysis by McNemar test, when appropriate. Significant variables at univariate analysis were include in a multivariable logistic regression analysis model with wild bootstrapping to account for collinearity and heteroscedasticity. Unsupervised agglomerative hierarchical clustering analysis was performed building the model based on SSDDI and the scores of its domains at 15 years. Disease characteristics at baseline were subsequently compared among the clusters. <h3>Results:</h3> A total of 102 pSS patients (97% female, mean age at diagnosis 45±12 years, mean disease duration 20±5 years) were included. Damage significantly increased from 1 (0-1.25) at 5 years, to 1 (0-2) at 10 years, and to 1 (0-3) at 15 years (p &lt;0.001 for omnibus test and for all pairwise comparisons) (Figure 1). ESSDAI score significantly reduced from 5 (3-8) at baseline, to 3 (2-6.25) at 5 years, 3 (2-7) at 10 years, and to 3 (1-7.25) at 15 years (p&lt;0.001 for omnibus test; at pairwise analysis differences were significant between baseline and each of the other timepoints). At linear regression analysis, ESSDAI at baseline significantly predicted damage at 15 years (β = 0.496, p&lt;0.001, CI 0.154 - 0.368), independently from age at diagnosis and comorbidities. Among ESSDAI domains, lymphadenopathy was an independent predictor of damage at 15 years (β = 0.274, p = 0.034, CI 0.255 – 3.331). Finally, the hierarchical clustering model based on SSDDI domains at 15 years identified five patient clusters with distinct damage patterns: Cluster 1 (C1) included almost all patients with salivary flow impairment and extra-glandular damage, C2 included patients with structural damage (loss of teeth and ocular damage) without salivary or tear flow impairment, C3 included patients who developed lymphoproliferative disease, C4 patients with isolated tear flow impairment and C5 patients with no damage (Figure 2). <h3>Conclusion:</h3> This multi-centre study outlines for the first time damage trajectories at 15 years of follow-up in a multi-center Italian pSS cohort. In our cohort, damage progressively builds up over at least 15 years. However, progression pattern is different among damage domains. The largest damage burden develops by year 5. Disease activity at baseline along with lymphadenopathy, independent of other disease features and comorbidities, significantly predict damage, strengthening the importance of early disease activity control to prevent damage. Interestingly, we identified 5 patient clusters with distinct damage patterns which, if reproduced in larger cohorts, may allow to tailor clinical and therapeutic approach to the disease since diagnosis and to reduce long-term damage accrual and, consequently, associated morbidity and mortality. <h3>REFERENCES:</h3> <b>NIL.</b> <h3>Acknowledgements:</h3> <b>NIL.</b> <h3>Disclosure of Interests:</h3> <b>None declared.</b>