Annie Cooper

Health-related utility values of patients with primary Sjögren's syndrome and its predictors

Objectives EuroQoL-5 dimension (EQ-5D) is a standardised preference-based tool for measurement of health-related quality of life and EQ-5D utility values can be converted to quality-adjusted life years (QALYs) to aid cost-utility analysis. This study aimed to evaluate the EQ-5D utility values of 639 patients with primary Sjögrens syndrome (PSS) in the UK. Methods Prospective data collected using a standardised pro forma were compared with UK normative data. Relationships between utility values and the clinical and laboratory features of PSS were explored. Results The proportion of patients with PSS reporting any problem in mobility, self-care, usual activities, pain/discomfort and anxiety/depression were 42.2%, 16.7%, 56.6%, 80.6% and 49.4%, respectively, compared with 5.4%, 1.6%, 7.9%, 30.2% and 15.7% for the UK general population. The median EQ-5D utility value was 0.691 (IQR 0.587–0.796, range −0.239 to 1.000) with a bimodal distribution. Bivariate correlation analysis revealed significant correlations between EQ-5D utility values and many clinical features of PSS, but most strongly with pain, depression and fatigue (R values>0.5). After adjusting for age and sex differences, multiple regression analysis identified pain and depression as the two most important predictors of EQ-5D utility values, accounting for 48% of the variability. Anxiety, fatigue and body mass index were other statistically significant predictors, but they accounted for <5% in variability. Conclusions This is the first report on the EQ-5D utility values of patients with PSS. These patients have significantly impaired utility values compared with the UK general population. EQ-5D utility values are significantly related to pain and depression scores in PSS.

Soluble molecule profiling and network analysis of primary Sjögren's Syndrome patient serum

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.

Factors influencing work disability in psoriatic arthritis: first results from a large UK multicentre study

OBJECTIVE The aim of this study was to determine the extent to which structural damage, clinical disease activity, demographic and social factors are associated with work disability (WD) in PsA. METHODS Four hundred patients fulfilling CASPAR (Classification Criteria for Psoriatic Arthritis) criteria for PsA were recruited from 23 hospitals across the UK. Demographic, socio-economic, work, clinical and radiographic data were collected. WD was assessed with the Work Productivity and Activity Impairment Specific Health Problem (WPAI-SHP) questionnaire reporting WD as a percentage of absenteeism (work time missed), presenteeism (impairment at work/reduced effectiveness) and work productivity loss (overall work impairment/absenteeism plus presenteeism). Logistic and linear regressions were conducted to investigate associations with WD. RESULTS Two hundred and thirty-six participants of any age were in work. Absenteeism, presenteeism and productivity loss rates were 14% (s.d. 29.0), 39% (s.d. 27.2) and 46% (s.d. 30.4), respectively. Ninety-two (26%) participants of working age were unemployed. Greater age, disease duration of 2-5 years and worse physical function were associated with unemployment. Patients reported that employer awareness and helpfulness exerted a strongly positive influence on remaining in employment. Higher levels of global and joint-specific disease activity and worse physical function were associated with greater levels of presenteeism and productivity loss among those who remained in work. CONCLUSION Reduced effectiveness at work was associated with measures of disease activity, whereas unemployment, considered the endpoint of WD, was associated with employer factors, age and disease duration. A longitudinal study is under way to determine whether treatment to reduce disease activity ameliorates WD in the real-world setting.

Fatigue in primary Sjögren's syndrome is associated with lower levels of proinflammatory cytokines.

Objectives This article reports relationships between serum cytokine levels and patient-reported levels of fatigue, in the chronic immunological condition primary Sjögrens syndrome (pSS). Methods Blood levels of 24 cytokines were measured in 159 patients with pSS from the United Kingdom Primary Sjögrens Syndrome Registry and 28 healthy non-fatigued controls. Differences between cytokines in cases and controls were evaluated using Wilcoxon test. Patient-reported scores for fatigue were evaluated, classified according to severity and compared with cytokine levels using analysis of variance. Logistic regression was used to determine the most important predictors of fatigue levels. Results 14 cytokines were significantly higher in patients with pSS (n=159) compared to non-fatigued healthy controls (n=28). While serum levels were elevated in patients with pSS compared to healthy controls, unexpectedly, the levels of 4 proinflammatory cytokines—interferon-γ-induced protein-10 (IP-10) (p=0.019), tumour necrosis factor-α (p=0.046), lymphotoxin-α (p=0.034) and interferon-γ (IFN-γ) (p=0.022)—were inversely related to patient-reported levels of fatigue. A regression model predicting fatigue levels in pSS based on cytokine levels, disease-specific and clinical parameters, as well as anxiety, pain and depression, revealed IP-10, IFN-γ (both inversely), pain and depression (both positively) as the most important predictors of fatigue. This model correctly predicts fatigue levels with reasonable (67%) accuracy. Conclusions Cytokines, pain and depression appear to be the most powerful predictors of fatigue in pSS. Our data challenge the notion that proinflammatory cytokines directly mediate fatigue in chronic immunological conditions. Instead, we hypothesise that mechanisms regulating inflammatory responses may be important.

Do the EULAR Sjögren’s syndrome outcome measures correlate with health status in primary Sjögren’s syndrome?

OBJECTIVE This study sets out to investigate the relationship between health status [EuroQol five-dimensions questionnaire (EQ-5D)] in primary SS and three of the European League Against Rheumatism (EULAR) SS outcome measures-the disease activity index (ESSDAI), the patient reported index (ESSPRI) and the sicca score. In particular, the goal was to establish whether there is a relationship between the EULAR outcome measures and quality of life. METHODS Health status was evaluated using a standardized measure developed by the EuroQol Group-the EQ5D. This permits calculation of two measures of health status: time trade-off (TTO) values and the EQ-5D visual analogue scale (VAS) scores. We used Spearmans rank correlation analysis to investigate the strength of association between health status and three EULAR measures of physician- and patient-reported disease activity in 639 patients from the UK primary SS registry (UKPSSR) cohort. RESULTS This study demonstrates that the EULAR SS disease-specific outcome measures are significantly correlated with health outcome values (P < 0.001). Higher scores on the ESSDAI, EULAR sicca score and ESSPRI are associated with poorer health states-i.e. lower TTO values and lower VAS scores. While all three are significantly correlated with TTO values and EQ-5D VAS scores, the effect is strongest for the ESSPRI. CONCLUSION This study provides further evidence supporting the use of ESSDAI, EULAR sicca score and ESSPRI measures in the clinic. We also discuss the need for disease-specific measures of health status and their comparison with standardized health outcome measures.

A Transcriptional Signature of Fatigue Derived from Patients with Primary Sjögren's Syndrome.

Background Fatigue is a debilitating condition with a significant impact on patients’ quality of life. Fatigue is frequently reported by patients suffering from primary Sjögren’s Syndrome (pSS), a chronic autoimmune condition characterised by dryness of the eyes and the mouth. However, although fatigue is common in pSS, it does not manifest in all sufferers, providing an excellent model with which to explore the potential underpinning biological mechanisms. Methods Whole blood samples from 133 fully-phenotyped pSS patients stratified for the presence of fatigue, collected by the UK primary Sjögren’s Syndrome Registry, were used for whole genome microarray. The resulting data were analysed both on a gene by gene basis and using pre-defined groups of genes. Finally, gene set enrichment analysis (GSEA) was used as a feature selection technique for input into a support vector machine (SVM) classifier. Classification was assessed using area under curve (AUC) of receiver operator characteristic and standard error of Wilcoxon statistic, SE(W). Results Although no genes were individually found to be associated with fatigue, 19 metabolic pathways were enriched in the high fatigue patient group using GSEA. Analysis revealed that these enrichments arose from the presence of a subset of 55 genes. A radial kernel SVM classifier with this subset of genes as input displayed significantly improved performance over classifiers using all pathway genes as input. The classifiers had AUCs of 0.866 (SE(W) 0.002) and 0.525 (SE(W) 0.006), respectively. Conclusions Systematic analysis of gene expression data from pSS patients discordant for fatigue identified 55 genes which are predictive of fatigue level using SVM classification. This list represents the first step in understanding the underlying pathophysiological mechanisms of fatigue in patients with pSS.

Effect of anti-TNF and conventional synthetic disease-modifying anti-rheumatic drug treatment on work disability and clinical outcome in a multicentre observational cohort study of psoriatic arthritis

Objective. To determine the effect of medical treatment on work disability in patients with active PsA in a real‐world setting. Methods. Four hundred patients with active PsA commencing or switching to anti‐TNF or conventional synthetic DMARD (csDMARD) were recruited to a multicentre UK prospective observational cohort study. Work disability was measured using the work productivity and activity‐specific health problem instrument and peripheral joint activity was measured with the disease activity in PsA composite measure. Results. Four hundred patients were recruited, of whom 229 (57.25%) were working (of any age). Sixty‐two patients of working age (24%) were unemployed. At 6 months there was a 10% improvement in presenteeism (P = 0.007) and a 15% improvement in work productivity (P = 0.001) among working patients commenced on csDMARDs (n = 164) vs a larger and more rapid 30% improvement in presenteeism (P < 0.001) and 40% improvement in work productivity (P < 0.001) among those commenced on anti‐TNF therapy (n = 65). Clinical response was poor among patients commenced on a csDMARD (n = 272), with an 8.4 point improvement in disease activity in PsA (P < 0.001) vs those commenced on anti‐TNF therapy (n = 121), who had a 36.8 point improvement (P < 0.001). Conclusion. We report significant and clinically meaningful improvements in both work disability and clinical outcomes after commencement of anti‐TNF therapy in a real‐world setting. Improvements in all outcomes among those commencing csDMARDs were slower and of a smaller magnitude.

Subjective and Objective Measures of Dryness Symptoms in Primary Sjögren’s Syndrome – Capturing the discrepancy

To develop a novel method for capturing the discrepancy between objective tests and subjective dryness symptoms (a sensitivity scale) and to explore predictors of dryness sensitivity.

SAT0242 How good are the eular sjögren’s syndrome disease activity index (ESSDAI), and EULAR sjögren’s syndrome patients reported index (ESSPRI) in predicting health status in primary sjögren’s syndrome?

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

FRI0448 Evaluating health status of 620 patients with primary sjÖgren’s syndrome using EQ-5D

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