Citation for published version (Harvard): Juarez, M, Toms, TE, De Pablo, P, Mitchell, S, Bowman, S, Nightingale, P, Price, EJ, Griffiths, B, Hunter, J, Gupta, M, Bombardieri, M, Sutcliffe, N, Pitzalis, C, Pease, C, Andrews, J, Emery, P, Regan, M, Giles, I, Isenberg, D, Moots, R, Collins, KS, Ng, WF & Kitas, GD 2014, 'Cardiovascular risk factors in women with primary Sjögren's syndrome: United Kingdom primary Sjögren's syndrome registry results' Arthritis Care & Research, vol. 66, no. 5, pp. 757-764. DOI: 10.1002/acr.22227

ObjectiveTo determine the prevalence of traditional cardiovascular risk factors using established definitions in a large cohort of clinically well-characterized primary Sjogren's syndrome (SS) patients and to compare them to healthy controls.MethodsData on cardiovascular risk factors in primary SS patients and controls were collected prospectively using a standardized pro forma. Cardiovascular risk factors were defined according to established definitions. The prevalence of cardiovascular risk factors in the primary SS group was determined and compared to that in the control group.ResultsPrimary SS patients had a higher prevalence of hypertension (28-50% versus 15.5-25.6%; P < 0.01) and hypertriglyceridemia (21% versus 9.5%; P = 0.002) than age- and sex-matched healthy controls. Furthermore, a significant percentage (56%) of hypertensive patients expected to be on antihypertensive treatment according to best practice was not receiving it.ConclusionPrimary SS patients are more than 2 times more likely to experience hypertension and hypertriglyceridemia than age- and sex-matched healthy controls. Additionally, hypertension is underdiagnosed and suboptimally treated in primary SS.

Background Over the past 2 years, the EULAR Sjogren's syndrome study group have developed 2 new instruments, ESSDAI and ESSPRI to measure systemic disease activity and overall symptom burden. The ESSPRI also generates an EULAR sicca score (ESS) which measures the overall symptom of dryness. These instruments are designed to be used as standardised outcome measures for clinical studies and trials. Therefore it is useful to investigate how well these instruments predict the health status of patients with primary Sjogren's syndrome (PSS). EQ-5D is a generic instrument that measure health outcome, the value sets can be converted to Time Trade Off (TTO) values representing the time a patient would be willing to give up to be freed from a reduced health state. In this study, we examined the relationship between ESSDAI and ESSPRI and the TTO values derived from EQ-5D. Objectives To evaluate the relationship between the two new instruments for the assessment of PSS (ESSDAI and ESSPRI) and health status of PSS patients. Methods Data including ESSDAI, ESSPRI and EQ-5D were prospectively collected from 633 PSS patients who have participated in the UK PSS registry (UKPSSR) using a standardised pro forma as previously described (1). TTO values were derived from the UK reference data provided by EuroQoL (the developer of the EQ-5D instrument) which has been transformed so that the values range from -1 to 1, with 1 being the number of years in perfect health state, 0 being dead and negative values representing health states worse than being dead. The relationships between the derived TTO values based on the health state of the patients and ESSDAI, ESSPRI as well as ESS were determined. Results The mean±SD TTO value of the PSS cohort was 0.624±0.301, with a range of -0.239 to 1. There were statistically significant correlations between TTO and ESSDAI, ESSPRI and ESS; TTO values decreased with increased ESSDAI, ESSPRI and ESS values (p<0.001 for all three). The strength of correlation was strongest with ESSPRI (R=-0.64), followed by ESS (R=-0.29) and ESSDAI (R=-0.15). Conclusions The recently developed EULAR PSS outcome assessment tools, in particular the ESSPRI, are useful predictors of the health status of PSS patients. Other UKPSSR collaborators: Moots R, Chadravarty K, Gendi N, Hamburger J, Richards A, Rauz S, Mulherin D, Kitas GD, Lloyd M, Lawson C, Clunie G, Knight S, Symmons D, Carr A, Carrozzo M, Figuereido F, Macleod I, Tarn JR, Foggo H, Edgar S,Young-Min S, Field A, Kaye S, Mewar D, Akil M, Dasgupta B, Fedele S, Porter S, Li C, Hall F. References Ng WF et al, Rheumatology, 2011;50:32-9. Disclosure of Interest None Declared

Background There is now clear evidence that supports the health promoting and disease preventing benefits of physical activity. To date, little research has been undertaken to evaluate physical activity levels in primary Sjögren’s syndrome (PSS) patients. Many symptoms of PSS such as musculoskeletal pain and fatigue may affect the ability and desire to participate in physical activity. Objectives To evaluate the levels of physical activity in individuals with PSS and its relationship to other clinical features of PSS. Methods Self-reported levels of physical activity from 273 PSS patients were collected using International Physical Activity Questionnaire (IPAQ) short form. The data were compared with healthy controls matched for age, sex and body mass index. Fatigue and other clinical aspects of PSS including disease status, dryness, daytime sleepiness, dysautonomia, anxiety and depression were assessed using validated tools. Univariate correlation and stepwise regression analyses were used to explore the relationships between physical activity levels and clinical features of PSS Results Individuals with PSS had significantly reduced levels of physical activity (median (interquartile range, IQR) MET*min/week: 1572 (2564) versus 3708 (6523), p<0.001), but similar levels of sedentary activity (median (IQR) min: 300 (188) versus 343 (214), p=0.532) compared to healthy individuals. The differences in physical activity were more profound at moderate (median (IQR) MET*min/week: 0 (480) versus 1560 (3330), p<0.001) and vigorous intensities (median (IQR) MET*min/week: 0 (480) versus 480 (1920), p<0.001). Univariate correlation analysis revealed significant association between physical activity and gender, fatigue, orthostatic and depressive symptoms. Sedentary activity did not correlate with fatigue. Stepwise regression analysis identified gender, physical fatigue and dryness as independent predictors of levels of physical activity. Conclusions Physical activity is reduced in people with PSS, particularly in moderate to vigorous intensity levels. Gender, fatigue and dryness are independently associated levels of physical activity. Acknowledgements This work was supported by the Medical Research Council (G0800629) and the British Sjögren’s Syndrome Association. This project also received infra-structure support from the Northumberland, Tyne and Wear Musculoskeletal Comprehensive Local Research Network and the Newcastle Clinical Research Facilities. Disclosure of Interest: None Declared

Background Primary Sjögren’s syndrome (pSS) is a multisystem autoimmune disease characterised by salivary and lacrimal gland inflammation leading to glandular destruction. The pathogenesis of pSS remains unclear, and research into pSS is made more challenging due to the heterogeneous clinical phenotypes among pSS patients. Several serum cytokines and chemokines have been linked with pSS pathogenesis, but their role in the various clinical manifestations in pSS have not been fully explored1,2. Objectives In this study, we examine the serum samples of a large cohort of clinically well-characterised PSS patients3 in order to determine whether serum cytokines and chemokines may be used to differentiate PSS patients from healthy controls, and if so, the relationship between these serum abnormalities and clinical phenotypes. Methods Serum levels of 24 different cytokines, chemokines and adhesion molecules for 150 pSS patients and 30 healthy controls were measured using Cytometric Bead Array.PSS patients were further classified into the following subsets: 1) Lymphoma; 2) No Lymphoma; 3) High systemic disease activity (ESSDAI score >12); 4) Low systemic disease activity (ESSDAI <1); 5) High residual glandular function (Oral salivary flow (OSF) >10ml/15min and Schirmer’s test >10cm); 6) Low residual glandular function (OSF <1ml/15min and Schirmer’s test <1cm); 7) Anti-Ro and Anti-La positive; 8) Anti-Ro and Anti-La negative. The relationship between analyte levels and clinical and laboratory parameters of PSS was examined using multivariate analysis and Mann-Whitney U testing; p-values were Bonferroni corrected for multiple comparisons. Results There were marked differences in the levels of many cytokines and chemokines between PSS patients and healthy controls, with a p value <0.001, statistically significant after Bonforroni’s correction for multiple comparisons. Serum IL4 and IL17 were found to be significantly higher in patients versus controls. Chemokines such as MIG (CXCL9), MIP1a (CCL3) and MIP1b (CCL4), IP10 (CXCL10), were also measured at higher levels in patient serum. Serum levels of IFNa, LTα and TNFα also differ significantly between patients and controls. Differences in cytokine levels were observed between patient subsets which were no longer significant after Bonferroni correction. Conclusions Differences in blood cytokine and chemokine levels between primary Sjogren’s patients and controls can be detected in serum. Serum MIG (CXCL9), MIP1a (CCL3) and MIP1b (CCL4), IP10 (CXCL10) IFNa, LTA and TNFa levels differ significantly between patients and controls. Our observations raise the possibility that these analytes may be important in disease pathogenesis. References Baturone, R. et al. Scand. J. Immunol. 2009;38:386. Szodoray, P. et al. Scand. J. Immunol. 2004;59:592. Ng, W.F. et al. Rheumatology 2010;50:32. Disclosure of Interest None Declared

Background EQ-5D is a standardised tool for measurement of health status and is an increasingly popular health-related quality of life instrument but has not been applied to patients with primary Sjögren’s syndrome (PSS). EQ-5D provides a simple descriptive profile, a single index value for health status and a visual analogue score (VAS). The key advantages of EQ-5D are that the instrument is preference-based, easy to complete and the value sets can be easily converted to Quality Adjusted Life Years (QALY) to aid cost-utility analysis. Objectives To evaluate the health status of a large cohort of patients with primary Sjogren’s syndrome in the UK using EQ-5D. Methods We evaluated the health status of 620 clinically well characterised PSS patients from the UK PSS registry (UKPSSR) who fulfil the American European Consensus Group classification criteria 2002. All data were collected prospectively using a standardised pro forma as previously described (1). Data were compared to the UK normative data provided by the EuroQoL. In addition, the relationship between the health status of PSS patients and various clinical and patient reported outcome measures of PSS were examined. Results The proportion of PSS patients reporting any problem in mobility, self-care, usual activities, pain/discomfort & anxiety/depression were 42.4, 16.9, 56.7, 81.1 & 49.6 (%) respectively compared to 5.4, 1.6, 7.9, 30.2 & 15.7 (%) in the general UK population. The mean±SD VAS score was 59.9±21.2, compared to 81.3±16.8 for the general UK population. Univariate correlation analysis showed that EQ-5D VAS correlated with many clinical features of PSS but most strongly with fatigue, depression and pain with R values >0.5. Among the laboratory measures, only IgG levels, paraproteins and C3 correlated with EQ-5D VAS. Hierarchical cluster analysis showed that depression and fatigue are the most important determinants of variations in health status in this PSS cohort. Conclusions To our knowledge, this is the first report on the health status of PSS patients using EQ-5D. PSS patients have significantly impaired health status compared to the UK general population. Depression and fatigue are the key determinants of health status in PSS. Our data adds to the growing body of evidence that effective management of fatigue is key to improving the health status of PSS patients. References Ng WF et al, Rheumatology, 2011;50:32-9. Other UKPSSR collaborators: Moots R, Chadravarty K, Gendi N, Hamburger J, Richards A, Rauz S, Mulherin D, Kitas GD, Lloyd M, Moore L, Lawson C, Clunie G, Knight S, Symmons D, Carr A, Carrozzo M, Figuereido F, Macleod I, Tarn J, Foggo H, Mann S, Young-Min S, Field A, Kaye S, Mewar D, Akil M, Dasgupta B, Fedele S, Porter S, Li C, Hall F. Disclosure of Interest None Declared

Background Primary Sjogren’s Syndrome (pSS) is a chronic autoimmune syndrome characterised by sicca symptoms, fatigue, musculoskeletal pain and an increased risk of lymphoma. Patient populations are notably heterogeneous in their symptoms, adding to the challenge of pSS research. This study utilises serum samples from the UK Primary Sjogren’s Syndrome Registry (UKPSSR) a large cohort of clinically well-characterised pSS patients and healthy controls with an aim to determine whether serum cytokines, chemokines and adhesion molecules may be used to differentiate pSS patients from healthy controls.