OP0094 LONG-TERM STABILITY OF SYMPTOM-BASED SUBTYPES IN SJOGREN’S DISEASE
Authors: J. Berry, J. Tarn, J. Casement, K. Thompson, D. Lendrem, J. E. Gottenberg, W. F. Ng
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> The Newcastle Sjogren's Stratification Tool (NSST) stratifies Sjogren's disease (SjD) patients into four subtypes.[1] These subtypes have distinct molecular profiles and may respond differently to immunomodulatory therapies.[1] NSST captures the patient experience using validated patient-reported outcomes (PROs), namely EULAR SS Patient Reported Index (ESSPRI) and Hospital Anxiety and Depression Scale (HADS) with the allocation of subtype membership then based on the probability of the patient belonging to a particular subtype. <h3>Objectives:</h3> To understand how symptom-based subtypes vary over time and factors influencing subtype change. Such data are important for understanding the patient experience and are vital if PROs, and PRO-guided stratification, are adopted in trial design and clinical management. <h3>Methods:</h3> 274 patients from the United Kingdom Primary Sjogren's Syndrome Registry (UKPSSR) with data permitting NSST subtype assignment from two study visits were included. The follow up interval was not standardised with a median of 4 years. The French Assessment of Systemic Signs and Evolution of Sjögren's Syndrome (ASSESS) cohort acted as an independent comparator. ASSESS follow up data were available at 12-month intervals for 5 years. 237 patients had data to assign NSST subtype at baseline and year 5; 134 patients had NSST data at all timepoints. Group analyses of significant differences were performed using Wilcoxon analysis, pairwise comparisons were performed using Tukey-Kramer HSD analysis. Fisher's Exact Test was used for categorical data. Logistic regression models were performed with the following covariates at baseline: age, sex, BMI, disease duration, Ro status, NSST probability score, ESSDAI score, C3, C4, IgG, WCC, current medication prescriptions, Chronic Conditions Indicator score (CCI) and polypharmacy score. Separate logistic regression models were used for the covariates: delta anxiety, delta depression, delta fatigue, delta pain, delta dryness, delta EQ-5D UK utility, delta CCI, delta polypharmacy score. Statistical tests and graphical rendering were performed using the R and SAS JMP Statistical Data Visualization software 23. <h3>Results:</h3> UKPSSR and ASSESS cohorts showed broadly similar proportion of subjects in each subtype and, similar baseline clinical characteristics except BMI. Several baseline characteristics differ significantly between the subtypes, most notably Ro+ status (higher in dryness-fatigue and low-symptom burden types) and BMI (higher in high-symptom burden type). Subtype membership was reasonably stable in both cohorts with 60% and 56% retaining subtype between the initial and final clinic visits. 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 also predicting increased subtype stability. <h3>Conclusion:</h3> 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. <h3>REFERENCES:</h3> [1] Tarn JR et al. Symptom-based stratification of patients with primary Sjogren's syndrome: multi-dimensional characterisation of international observational cohorts and reanalyses of randomised clinical trials. Lancet Rheumatol. 2019 Oct 1;1(2):e85–94. <h3>Acknowledgements:</h3> This work was supported in part by the Medical Research Council (Grant REFERENCES: G0800629 &amp; MR/J002720/1), FOREUM, NECESSITY, NIHR Biomedical Research Centre at Newcastle University and the Newcastle upon Tyne Hospitals NHS Trust. <h3>Disclosure of Interests:</h3> Joe Berry: None declared, Jessica Tarn: None declared, John Casement: None declared, Kyle Thompson: None declared, Dennis Lendrem: None declared, Jacques-Eric Gottenberg: None declared, Wan-Fai Ng WFN has undertaken clinical trials and provided consultancy or expert advice in the area of Sjögren's syndrome to the following companies: GlaxoSmithKline, MedImmune, UCB, Abbvie, Takeda, Resolves Therapeutics, Sanofi, Novartis, Bain Capitals and Argenx., WFN has undertaken clinical trials and provided consultancy or expert advice in the area of Sjögren's syndrome to the following companies: GlaxoSmithKline, MedImmune, UCB, Abbvie, Takeda, Resolves Therapeutics, Sanofi, Novartis, Bain Capitals and Argenx.