3 research outputs found
Symptom-based stratification of patients with primary Sjögren's syndrome: multi-dimensional characterisation of international observational cohorts and reanalyses of randomised clinical trials
Background
Heterogeneity is a major obstacle to developing effective treatments for patients with primary Sjögren's syndrome. We aimed to develop a robust method for stratification, exploiting heterogeneity in patient-reported symptoms, and to relate these differences to pathobiology and therapeutic response.
Methods
We did hierarchical cluster analysis using five common symptoms associated with primary Sjögren's syndrome (pain, fatigue, dryness, anxiety, and depression), followed by multinomial logistic regression to identify subgroups in the UK Primary Sjögren's Syndrome Registry (UKPSSR). We assessed clinical and biological differences between these subgroups, including transcriptional differences in peripheral blood. Patients from two independent validation cohorts in Norway and France were used to confirm patient stratification. Data from two phase 3 clinical trials were similarly stratified to assess the differences between subgroups in treatment response to hydroxychloroquine and rituximab.
Findings
In the UKPSSR cohort (n=608), we identified four subgroups: Low symptom burden (LSB), high symptom burden (HSB), dryness dominant with fatigue (DDF), and pain dominant with fatigue (PDF). Significant differences in peripheral blood lymphocyte counts, anti-SSA and anti-SSB antibody positivity, as well as serum IgG, Îș-free light chain, ÎČ2-microglobulin, and CXCL13 concentrations were observed between these subgroups, along with differentially expressed transcriptomic modules in peripheral blood. Similar findings were observed in the independent validation cohorts (n=396). Reanalysis of trial data stratifying patients into these subgroups suggested a treatment effect with hydroxychloroquine in the HSB subgroup and with rituximab in the DDF subgroup compared with placebo.
Interpretation
Stratification on the basis of patient-reported symptoms of patients with primary Sjögren's syndrome revealed distinct pathobiological endotypes with distinct responses to immunomodulatory treatments. Our data have important implications for clinical management, trial design, and therapeutic development. Similar stratification approaches might be useful for patients with other chronic immune-mediated diseases.
Funding
UK Medical Research Council, British Sjogren's Syndrome Association, French Ministry of Health, Arthritis Research UK, Foundation for Research in Rheumatology
LâinterdisciplinaritĂ© en pratiqueâ: retour dâexpĂ©rience de la deuxiĂšme Ă©cole dâĂ©tĂ© australe sur la vulnĂ©rabilitĂ© du patrimoine rĂ©cifal (EEA VulPaRe 2016)
International audienceIn November 2016, the Second Austral Summer School âVulnerability of coral reefs heritageâ (EEA VulPaRe 2016) took place at Toliara (Madagascar). The school was funded and organised by IRD (French Research Institute for Development) and IHSM (Institute of Halieutics and Marine Science, University of Toliara), and proposed an interdisciplinary approach to the study of coral reefs. Environmental issues, different types of knowledge and valorisation of coral reefs were addressed by means of lectures, seminars, discussions and fieldwork. In this paper, the participants of EEA VulPaRe 2016 provide a critical feedback on this original interdisciplinary research training.En novembreâ2016, sâest tenue Ă Toliara, dans le sud-ouest de Madagascar, la deuxiĂšme Ă©cole dâĂ©tĂ© australe sur la vulnĂ©rabilitĂ© du patrimoine rĂ©cifal (EEA VulPaRe). CoorganisĂ©e par lâIRD (Institut de recherche pour le dĂ©veloppement, France) et lâIHSM (Institut halieutique et des sciences marines de lâUniversitĂ© de Toliara, Madagascar), cette formation a proposĂ© une approche interdisciplinaire de la thĂ©matique des rĂ©cifs coralliens. Elle a Ă©tĂ© dispensĂ©e sous la forme de cours magistraux, de pratiques de terrain et de dĂ©bats portant sur les questions environnementales, de connaissance, de valorisation et de conservation de ces milieux. Les participants de lâEEA VulPaRe 2016 souhaitent, Ă travers le prĂ©sent article, donner Ă la communautĂ© scientifique un retour dâexpĂ©rience critique sur une dĂ©marche originale de formation Ă la recherche interdisciplinaire
Practicing interdisciplinarity: a review of the Second Austral Summer School on vulnerability of coral reefs heritage (EEA VulPaRe 2016)
In November 2016, the Second Austral Summer School âVulnerability of coral reefs heritageâ (EEA VulPaRe 2016) took place at Toliara (Madagascar). The school was funded and organised by IRD (French Research Institute for Development) and IHSM (Institute of Halieutics and Marine Science, University of Toliara), and proposed an interdisciplinary approach to the study of coral reefs. Environmental issues, different types of knowledge and valorisation of coral reefs were addressed by means of lectures, seminars, discussions and fieldwork. In this paper, the participants of EEA VulPaRe 2016 provide a critical feedback on this original interdisciplinary research training.En novembreâ2016, sâest tenue Ă Toliara, dans le sud-ouest de Madagascar, la deuxiĂšme Ă©cole dâĂ©tĂ© australe sur la vulnĂ©rabilitĂ© du patrimoine rĂ©cifal (EEA VulPaRe). CoorganisĂ©e par lâIRD (Institut de recherche pour le dĂ©veloppement, France) et lâIHSM (Institut halieutique et des sciences marines de lâUniversitĂ© de Toliara, Madagascar), cette formation a proposĂ© une approche interdisciplinaire de la thĂ©matique des rĂ©cifs coralliens. Elle a Ă©tĂ© dispensĂ©e sous la forme de cours magistraux, de pratiques de terrain et de dĂ©bats portant sur les questions environnementales, de connaissance, de valorisation et de conservation de ces milieux. Les participants de lâEEA VulPaRe 2016 souhaitent, Ă travers le prĂ©sent article, donner Ă la communautĂ© scientifique un retour dâexpĂ©rience critique sur une dĂ©marche originale de formation Ă la recherche interdisciplinaire