Real-world damage accrual in Sjögren’s disease: a 5-year multicentre GIRRCS cohort analysis

Introduction: Primary Sjögren's disease (SD) is a systemic autoimmune disorder causing glandular dysfunction, sicca symptoms and extraglandular manifestations, which impair quality of life. Data on early irreversible damage and its predictors remain limited. Methods: We conducted a multicentre retrospective cohort study of 429 adult patients with SD from the Gruppo Italiano di Ricerca in Reumatologia Clinica e Sperimentale network with ≥1 year of follow-up. Baseline assessments included disease activity (European League Against Rheumatism (EULAR), Sjögren's Syndrome Disease Activity Index (ESSDAI)), patient-reported symptoms (EULAR Sjögren's Syndrome Patient Reported Index (ESSPRI)), C reactive protein (CRP), Schirmer's test (ST) and autoantibody status. Irreversible damage was evaluated using the Sjögren's Syndrome Damage Index (SSDI) across ocular, oral and systemic domains. Predictors of damage accrual were analysed using Cox proportional hazards models and Kaplan-Meier curves. Exploratory Least Absolute Shrinkage and Selection Operator (LASSO) and principal component analysis (PCA) analyses assessed domain-specific contributions and relationships between subjective and objective measures. Results: At baseline, 48% of patients had SSDI≥1: ocular 25.4%, systemic 22.5% and oral 14.3%. After 5 years, 65% had cumulative damage: ocular 34.2%, oral 21.7% and systemic 40.8%. Higher baseline ESSDAI predicted damage across all domains. Elevated ESSPRI was associated with oral damage, while abnormal ST strongly predicted ocular damage. Anti-Ro/La antibodies, elevated CRP and recurrent oral infections were linked to higher domain-specific damage. LASSO analyses showed glandular, peripheral nervous system and pulmonary ESSDAI domains independently contributed to systemic damage. PCA confirmed that patient-reported symptoms and systemic activity represent complementary, independent dimensions. Conclusion: Irreversible damage in SD occurs early, often present at diagnosis and affects multiple organ domains. Early identification of high-risk patients, based on clinical, serological and patient-reported measures, may enable timely interventions to prevent further damage, guide treatment and improve long-term outcomes.