Stability of symptom-based subtypes in Sjogren's disease

Abstract

Objectives: The Newcastle Sjogren's Stratification Tool (NSST) stratifies Sjogren's disease patients into four subtypes. Understanding the stability of the subtypes is vital if symptom-based stratification is to be more broadly adopted. In this study, we stratify patients longitudinally to understand how symptom-based subtypes vary over time and factors influencing subtype change.

Methods: 274 patients from the United Kingdom Primary Sjögren's Syndrome Registry (UKPSSR) with data permitting NSST subtype assignment from two study visits were included. The French Assessment of Systemic Signs and Evolution of Sjogren's Syndrome (ASSESS) cohort (n=237) acted as an independent comparator. Group analyses of significant differences were performed, with logistic regression models used to assess covariates of subtype stability.

Results: UKPSSR and ASSESS cohorts showed a broadly similar proportion of subjects in each subtype and similar baseline clinical characteristics except body mass index (BMI). Several baseline characteristics differ significantly between the subtypes, most notably anti-Ro status and BMI. Subtype membership was reasonably stable in both cohorts with 60% and 57% retaining subtype. The high-symptom burden subtype was the most stable over time with 70% and 67% retaining subtype. Higher baseline probability score was the greatest predictor of subtype stability with higher C4 levels, antidepressant use, and a higher CCI score also predicting increased stability.

Conclusion: NSST subtype membership remains stable over time in a large proportion of patients. When subtype transition is associated with factors at baseline, it is most strongly associated with an uncertain subtype allocation. Our findings support the hypothesis that symptom-based subtypes reflect genuine pathobiological endotypes and therefore maybe important to consider in trial design and clinical management.

Keywords: Autoantibodies; Classification; Fatigue; Patient Reported Outcome Measures; Sjogren's Syndrome.

Figure 1. NSST long-term subtype stability. (A) UKPSSR cohort: 274 patients classified at baseline and follow-up as an alluvial plot. (B) ASSESS cohort: 237 patients classified at baseline and 60 months follow-up as an alluvial plot. Coloured ribbons represent the movement of patients from the initial subgroup to follow-up subgroup. Our analysis highlights that for a large proportion of patients NSST subtype membership remains stable over time. ASSESS, Assessment of Systemic Signs and Evolution of Sjögren’s Syndrome; DDF, dryness dominant with fatigue; HSB, high symptom burden; LSB, low symptom burden; NSST, Newcastle Sjogren’s Stratification Tool; PDF, pain dominant with fatigue; UKPSSR, United Kingdom Primary Sjögren’s Syndrome Registry.

Figure 2. Tracking the ASSESS cohort over 60 months. Figure shows the NSST baseline probability score, the baseline subtype and the subtype at 12-month intervals of patients within the ASSESS cohort. ASSESS, Assessment of Systemic Signs and Evolution of Sjögren’s Syndrome; DDF, dryness dominant with fatigue; HSB, high symptom burden; LSB, low symptom burden; NSST, Newcastle Sjogren’s Stratification Tool; PDF, pain dominant with fatigue;.