Symptom-Based Stratification Reveals Pathobiologic Endotypes With Distinct Treatment Responses in Sjogren Syndrome

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Researchers aimed to develop a stratification method to evaluate symptom prevalence and distinct treatment responses in patients with Sjogren syndrome.

Stratification of patients with Sjogren syndrome into 4 subgroups may determine symptom prevalence and distinct responses to treatment, according to study results published in the Lancet Rheumatology.

The study included data from patients in the United Kingdom Primary Sjogren Syndrome Registry who fulfilled the 2002 American European Consensus Group classification criteria between August 2009 and September 2011. Researchers performed hierarchical cluster analysis using 5 common symptoms associated with primary Sjogren syndrome, including pain, fatigue, dryness, anxiety, and depression. They also used multinomial logistic regression to identify subgroups from the registry.

Among the identified subgroups, the researchers assessed clinical and biologic differences, including transcriptional differences in peripheral blood. They confirmed stratification in patients with Sjogren syndrome using data from 2 independent validation cohorts in Norway and France.

In addition, the researchers used data from 2 phase 3 clinical trials ( Identifier: NCT00632866 and European Clinical Trials Database Number: 2010‐021430‐64) to determine the differences in treatment response to hydroxychloroquine and rituximab between subgroups.

Among 608 participants in the UK Primary Sjogren Syndrome Registry cohort, the researchers identified 4 subgroups: low symptom burden, high symptom burden, dryness dominant with fatigue, and pain dominant with fatigue.

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Results of the study indicated that the subgroups had significant differences in peripheral blood lymphocyte counts, anti-Sjogren-syndrome-related antigen A positivity, anti-Sjogren-syndrome-related antigen B positivity, serum immunoglobulin G, κ-free light chain concentrations, β2-microglobulin concentrations, and chemokine (C-X-C motif) ligand 13 concentration. In addition, the identified subgroups had different expressions of transcriptomic modules in peripheral blood. There were no statistically significant differences in age, sex, disease duration, and European League Against Rheumatism Sjogren syndrome disease activity index. Researchers observed similar results in the independent validation cohorts (n=396).

After analyzing data from the phase 3 clinical trials, the results indicated that compared with placebo, patients in the high symptom burden subgroup had a treatment response to hydroxychloroquine. Also, compared with placebo, the dryness dominant with fatigue subgroup had a treatment response to rituximab.

Study limitations included the clustering analysis design, and the fact that although data from multiple studies were used for the analysis, none of them were designed with stratification as the primary goal.

“[O]ur data show that symptom-based stratification is a robust and clinically meaningful approach, addressing the clinical heterogeneity of patient experience and reflecting differences in [pathobiologic] profiles and therapeutic responses,” the researchers wrote.

Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.


Tarn JR, Howard-Tripp N, Lendrem DW, et al. Symptom-based stratification of patients with primary Sjogren’s syndrome: multi-dimensional characterisation of international observed cohorts and reanalyses of randomised clinical trials. Lancet Rheumatol. 2019;1(2):PE85-94.