Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, Tyne and Wear, UK.
Clinical and Translational Medicine Research Centre, University of Sunderland, Sunderland, UK.
RMD Open. 2024 Nov 24;10(4):e004914. doi: 10.1136/rmdopen-2024-004914.
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.
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.
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.
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.
纽卡斯尔干燥综合征分层工具（NSST）将干燥综合征患者分为四个亚型。如果要更广泛地采用基于症状的分层，了解亚型的稳定性至关重要。在这项研究中，我们对患者进行纵向分层，以了解基于症状的亚型如何随时间变化，以及影响亚型变化的因素。
纳入了来自英国原发性干燥综合征登记处（UKPSSR）的 274 名患者，这些患者在两次研究访问中均有数据可用于 NSST 亚型分配。法国评估系统性体征和干燥综合征演变（ASSESS）队列（n=237）作为独立对照。对具有统计学意义的差异进行组分析，并使用逻辑回归模型评估亚型稳定性的协变量。
UKPSSR 和 ASSESS 队列中每个亚型的受试者比例大致相似，基线临床特征也相似，除了体重指数（BMI）。亚型之间存在几个基线特征存在显著差异，最显著的是抗 Ro 状态和 BMI。在两个队列中，亚型成员身份相对稳定，分别有 60%和 57%保留了亚型。高症状负担亚型随时间最稳定，分别有 70%和 67%保留了亚型。较高的基线概率评分是亚型稳定性的最大预测因素，较高的 C4 水平、抗抑郁药的使用以及 CCI 评分较高也预示着稳定性增加。
在很大一部分患者中，NSST 亚型成员身份随时间保持稳定。当亚型转换与基线因素相关时，与不确定的亚型分配关系最密切。我们的研究结果支持这样一种假设，即基于症状的亚型反映了真正的病理生物学内型，因此在临床试验设计和临床管理中可能很重要。
