Elizabeth Price

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.

The TRACTISS Protocol: a randomised double blind placebo controlled clinical TRial of Anti-B-Cell Therapy In patients with primary Sjögren's Syndrome

BackgroundPrimary Sjögren’s Syndrome (PSS) mainly affects women (9:1 female:male ratio) and is one of the commonest autoimmune diseases with a prevalence of 0.1 – 0.6% of adult women. For patients with PSS there is currently no effective therapy that can alter the progression of the disease. The aim of the TRACTISS study is to establish whether in patients with PSS, treatment with rituximab improves clinical outcomes.Methods/designTRACTISS is a UK multi-centre, double-blind, randomised, controlled, parallel group trial of 110 patients with PSS. Patients will be randomised on a 1:1 basis to receive two courses of either rituximab or placebo infusion in addition to standard therapy, and will be followed up for up to 48 weeks. The primary objective is to assess the extent to which rituximab improves symptoms of fatigue and oral dryness. Secondary outcomes include ocular dryness, salivary flow rates, lacrimal flow, patient quality of life, measures of disease damage and disease activity, serological and peripheral blood biomarkers, and glandular histology and composition.DiscussionThe TRACTISS trial will provide direct evidence as to whether rituximab in patients with PSS leads to an improvement in patient symptoms and a reduction in disease damage and activity.Trial registrationUKCRN Portfolio ID:9809 ISRCTN65360827.

Randomized controlled trial of rituximab and cost-effectiveness analysis in treating fatigue and oral dryness in primary Sjogren's Syndrome

To investigate whether rituximab, an anti–B cell therapy, improves symptoms of fatigue and oral dryness in patients with primary Sjögrens syndrome (SS).

Cardiovascular risk factors in women with primary Sjögren's syndrome: United Kingdom primary Sjögren's syndrome registry results

To determine the prevalence of traditional cardiovascular risk factors using established definitions in a large cohort of clinically well‐characterized primary Sjögrens syndrome (SS) patients and to compare them to healthy controls.

Estimating Indirect Costs in Primary Sjogren's Syndrome

Objective. To estimate the indirect costs associated with primary Sjögren’s syndrome (pSS) compared with rheumatoid arthritis (RA) and community controls. Methods. Data were obtained from 84 women patients with pSS as part of a study to develop a systemic activity measure, from 87 consecutive women patients with RA attending a hospital clinic, and from 96 women community controls on a general practice list. A modified economic component of the Stanford Health Assessment Questionnaire was used to assess lost productivity. Results. Using a conservative model, the estimated total annual indirect costs (95% CI) were £7677 (£5560, £9794) for pSS, £10,444 (£8206, £12,681) for RA, and £892 (£307, £1478) for controls. Using a model that maximizes the estimates, the equivalent figures were £13,502 (£9542, £17,463), £17,070 (£13,112, £21,028), and £3382 (£2187, £4578), respectively. These were all significantly greater at p < 0.001 for patient groups than for the control group. Conclusion. pSS is associated with significantly increased indirect costs equivalent to 69%–83% of that for patients with RA. This needs to be taken into account when evaluating the overall economic consequences of pSS.

[Accepted Manuscript] Randomized Controlled Trial of Rituximab and cost-effectiveness analysis in treating fatigue and oral dryness in primary Sjogren's Syndrome.

To investigate whether rituximab, an anti–B cell therapy, improves symptoms of fatigue and oral dryness in patients with primary Sjögrens syndrome (SS).

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.

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.

Eligibility for clinical trials in primary Sjogren's syndrome: lessons from the UK Primary Sjogren's Syndrome Registry.

OBJECTIVEnTo identify numbers of participants in the UK Primary Sjögrens Syndrome Registry (UKPSSR) who would fulfil eligibility criteria for previous/current or potential clinical trials in primary SS (pSS) in order to optimize recruitment.nnnMETHODSnWe did a retrospective analysis of UKPSSR cohort data of 688 participants who had pSS with evaluable data.nnnRESULTSnIn relation to previous/current trials, 75.2% fulfilled eligibility for the Belimumab in Subjects with Primary Sjögrens Syndrome study (Belimumab), 41.4% fulfilled eligibility for the Trial of Remicade in primary Sjögrens syndrome study (Infliximab), 35.4% for the Efficacy of Tocilizumab in Primary Sjögrens Syndrome study (Tocilizumab), 31.6% for the Tolerance and Efficacy of Rituximab in Sjögrens Disease study (Rituximab), 26.9% for the Trial of anti-B-cell therapy in pSS study (Rituximab) and 26.6% for the Efficacy and Safety of Abatacept in Patients With Primary Sjögrens Syndrome study (Abatacept). If recent measures of outcome, such as the EULAR Sjögrens Syndrome Patient Reported Index (ESSPRI) score ⩾5 (measure of patient symptoms) and the EULAR Sjögrens Syndrome Disease Activity Index (ESSDAI) score ⩾5 (measure of systemic disease activity) are incorporated into a study design, with requirements for an unstimulated salivary flow >0 and anti-Ro positivity, then the pool of eligible participants is reduced to 14.3%.nnnCONCLUSIONnThe UKPSSR identified a number of options for trial design, including selection on ESSDAI ⩾5, ESSPRI ⩾5 and serological and other parameters.

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

OBJECTIVEnThis 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.nnnMETHODSnHealth 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.nnnRESULTSnThis 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.nnnCONCLUSIONnThis 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.