Risk factors for disease progression in primary Sjögren's syndrome patients with low disease activity: a multicenter registry-based cohort study

Abstract

Background and objectives: Primary Sjögren's syndrome (pSS) patients with low disease activity remain at risk for disease progression, yet predictive factors are poorly understood. We aimed to identify risk factors for disease worsening in pSS patients with initially low disease activity.

Methods: We conducted a registry-based cohort study using prospectively collected data from the Chinese Rheumatism Data Center (CRDC). Patients with pSS meeting either 2002 AECG or 2016 ACR/EULAR classification criteria and baseline ESSDAI < 5 were included. Disease worsening was defined as ESSDAI increase ≥ 3 points during follow-up. Cox proportional hazards regression with LASSO selection identified independent risk factors.

Results: Among 745 patients (median age 46 years, 97.4% female), 214 (28.7%) experienced disease worsening during median follow-up of 36 months. Univariate analysis and LASSO regression selected 11 variables for multivariate analysis. Independent risk factors were renal involvement (HR = 6.18, 95%CI: 2.44-15.61, P < 0.001), anti-Sm positivity (HR = 2.10, 95%CI: 1.12-3.93, P = 0.020), and dry eye symptoms (HR = 1.46, 95%CI: 1.06-2.00, P = 0.022).

Conclusions: Nearly one-third of pSS patients with low disease activity experience disease worsening. Renal involvement, anti-Sm antibodies, and dry eye symptoms independently predict progression. Risk stratification based on these factors can identify patients requiring closer monitoring and potentially more intensive therapeutic intervention. Key Points • This multicenter registry study of 745 primary Sjögren's syndrome patients with low disease activity found that 28.7% experienced disease worsening during follow-up, highlighting that low disease activity does not guarantee disease stability. • Three independent predictors of disease progression were identified: renal involvement (HR = 6.18), anti-Sm antibody positivity (HR = 2.10), and dry eye symptoms (HR = 1.46). • Conventional synthetic DMARDs were not significantly associated with reduced disease worsening in adjusted models, highlighting the need for randomized trials to properly evaluate therapeutic strategies.

Keywords: Disease progression; ESSDAI; Primary Sjögren's syndrome; Risk factors.