Revision to the musculoskeletal domain of the BILAG-2004 index to incorporate ultrasound findings.

OBJECTIVES: To improve the definitions of inflammatory arthritis within the musculoskeletal (MSK) domain of the BILAG-2004 index by incorporating imaging findings and clinical features predictive of response to treatment. METHODS: The BILAG MSK Subcommittee proposed revisions to the BILAG-2004 index definitions of inflammatory arthritis, based on review of evidence in two recent studies. Data from these studies were pooled and analysed to determine the impact of the proposed changes on the severity grading of inflammatory arthritis. RESULTS: The revised definition for severe inflammatory arthritis includes definition of 'basic activities of daily living'. For moderate inflammatory arthritis, it now includes synovitis, defined by either observed joint swelling or MSK US evidence of inflammation in joints and surrounding structures. For mild inflammatory arthritis, the definition now includes reference to symmetrical distribution of affected joints and guidance on how US may help re-classify patients as moderate or no inflammatory arthritis. Data from two recent SLE trials were analysed (219 patients). A total of 119 (54.3%) were graded as having mild inflammatory arthritis (BILAG-2004 Grade C). Of these, 53 (44.5%) had evidence of joint inflammation (synovitis or tenosynovitis) on US. Applying the new definition increased the number of patients classified as moderate inflammatory arthritis from 72 (32.9%) to 125 (57.1%), while patients with normal US (n = 66/119) could be recategorized as BILAG-2004 Grade D (inactive disease). CONCLUSIONS: Proposed changes to the definitions of inflammatory arthritis in the BILAG-2004 index will result in more accurate classification of patients who are more or less likely to respond to treatment.

Outcomes of children born to mothers with systemic lupus erythematosus exposed to hydroxychloroquine or azathioprine.

OBJECTIVES: HCQ and AZA are used to control disease activity and reduce risk of flare during pregnancy in patients with SLE. The aim of this study was to determine the outcomes of children born to mothers with SLE exposed to HCQ or AZA during pregnancy and breast-feeding. METHODS: Women attending UK specialist lupus clinics with children ≤17 years old, born after SLE diagnosis, were recruited to this retrospective study. Data were collected using questionnaires and from clinical record review. Factors associated with the outcomes of low birth weight and childhood infection were determined using multivariable mixed-effects logistic regression models. RESULTS: We analysed 284 live births of 199 mothers from 10 UK centres. The first pregnancies of 73.9% of mothers (147/199) were captured in the study; (60.4%) (150/248) and 31.1% (87/280) children were exposed to HCQ and AZA, respectively. There were no significant differences in the frequency of congenital malformations or intrauterine growth restriction between children exposed or not to HCQ or AZA. AZA use was increased in women with a history of hypertension or renal disease. Although AZA was associated with low birth weight in univariate models, there was no significant association in multivariable models. In adjusted models, exposure to AZA was associated with increased reports of childhood infection requiring hospital management [odds ratio 2.283 (1.003, 5.198), P = 0.049]. CONCLUSIONS: There were no significant negative outcomes in children exposed to HCQ in pregnancy. AZA use was associated with increased reporting of childhood infection, which warrants further study.

The BILAG-2004 index is associated with development of new damage in SLE.

OBJECTIVE: To determine whether BILAG-2004 index is associated with the development of damage in a cohort of SLE patients. Mortality and development of damage were examined. METHODS: This was a multicentre longitudinal study. Patients were recruited within 12 months of achieving fourth ACR classification criterion for SLE. Data were collected on disease activity, damage, SLE-specific drug exposure, cardiovascular risk factors, antiphospholipid syndrome status and death at every visit. This study ran from 1 January 2005 to 31 December 2017. Descriptive statistics were used to analyse mortality and development of new damage. Poisson regression was used to examine potential explanatory variables for development of new damage. RESULTS: A total of 273 SLE patients were recruited with total follow-up of 1767 patient-years (median 73.4 months). There were 6348 assessments with disease activity scores available for analysis. During follow-up, 13 deaths and 114 new damage items (in 83 patients) occurred. The incidence rate for development of damage was higher in the first 3 years before stabilizing at a lower rate. Overall rate for damage accrual was 61.1 per 1000 person-years (95% CI: 50.6, 73.8). Analysis showed that active disease scores according to BILAG-2004 index (systems scores of A or B, counts of systems with A and BILAG-2004 numerical score) were associated with development of new damage. Low disease activity (LDA) states [BILAG-2004 LDA and BILAG Systems Tally (BST) persistent LDA] were inversely associated with development of damage. CONCLUSIONS: BILAG-2004 index is associated with new damage. BILAG-2004 LDA and BST persistent LDA can be considered as treatment targets.

Comparison of Responsiveness of British Isles Lupus Assessment Group 2004 Index, Systemic Lupus Erythematosus Disease Activity Index 2000, and British Isles Lupus Assessment Group 2004 Systems Tally.

OBJECTIVE: To compare the responsiveness of the British Isles Lupus Assessment Group 2004 index (BILAG-2004) and the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) disease activity indices and to determine whether there was any added value in combining BILAG-2004, BILAG-2004 system tally (BST), or simplified BST (sBST) with SLEDAI-2K. METHODS: This was a multicenter longitudinal study of SLE patients. Data were collected on BILAG-2004, SLEDAI-2K, and therapy on consecutive assessments in routine practice. The external responsiveness of the indices was assessed by determining the relationship between change in disease activity and change in therapy between 2 consecutive visits. Comparison of indices and their derivatives was performed by assessing the main effects of the indices using logistic regression. Receiver operating characteristic curves analysis was used to describe the performance of these indices individually and in various combinations, and comparisons of area under the curve were performed. RESULTS: There were 1,414 observations from 347 patients. Both BILAG-2004 and SLEDAI-2K maintained an independent relationship with change in therapy when compared. There was some improvement in responsiveness when continuous SLEDAI-2K variables (change in score and score of previous visit) were combined with BILAG-2004 system scores. Dichotomization of BILAG-2004 or SLEDAI-2K resulted in poorer performance. BST and sBST had similar responsiveness as the combination of SLEDAI-2K variables and BILAG-2004 system scores. There was little benefit in combining SLEDAI-2K with BST or sBST. CONCLUSION: The BILAG-2004 index had comparable responsiveness to SLEDAI-2K. There was some benefit in combining both indices. Dichotomization of BILAG-2004 and SLEDAI-2K leads to suboptimal performance. BST and sBST performed well on their own; sBST is recommended for its simplicity and clinical meaningfulness.

Ultrasound to identify systemic lupus erythematosus patients with musculoskeletal symptoms who respond best to therapy: the US Evaluation For mUsculoskeletal Lupus longitudinal multicentre study.

OBJECTIVES: To determine whether SLE patients with inflammatory joint symptoms and US synovitis/tenosyovitis achieve better clinical responses to glucocorticoids compared with patients with normal scans. Secondary objectives included identification of clinical features predicting US synovitis/tenosynovitis. METHODS: In a longitudinal multicentre study, SLE patients with physician-diagnosed inflammatory joint pain received intramuscular methylprednisolone 120 mg once. Clinical assessments, patient-reported outcomes and bilateral hand/wrist USs were collected at 0, 2 and 6 weeks. The primary outcome (determined via internal pilot) was the early morning stiffness visual analogue scale (EMS-VAS) at 2 weeks, adjusted for baseline, comparing patients with positive (greyscale ≥2 and/or power Doppler ≥1) and negative US. Post hoc analyses excluded FM. RESULTS: Of 133 patients, 78 had a positive US. Only 53 (68%) of these had one or more swollen joint. Of 66 patients with one or more swollen joint, 20% had a negative US. A positive US was associated with joint swelling, symmetrical small joint distribution and serology. The primary endpoint was not met: in the full analysis set (N = 133) there was no difference in baseline-adjusted EMS-VAS at week 2 [-7.7 mm (95% CI -19.0, 3.5); P = 0.178]. After excluding 32 patients with FM, response was significantly better in patients with a positive US at baseline [baseline-adjusted EMS-VAS at 2 weeks -12.1 mm (95% CI -22.2, -0.1); P = 0.049]. This difference was greater when adjusted for treatment [-12.8 mm (95% CI -22, -3); P = 0.007]. BILAG and SLEDAI responses were higher in US-positive patients. CONCLUSION: In SLE patients without FM, those with a positive US had a better clinical response to therapy. Imaging-detected synovitis/tenosynovitis may be considered to decide on therapy and enrich clinical trials.

Flares in patients with systemic lupus erythematosus.

OBJECTIVE: SLE is characterized by relapses and remissions. We aimed to describe the frequency, type and time to flare in a cohort of SLE patients. METHODS: SLE patients with one or more 'A' or 'B' BILAG-2004 systems meeting flare criteria ('new' or 'worse' items) and requiring an increase in immunosuppression were recruited from nine UK centres and assessed at baseline and monthly for 9 months. Subsequent flares were defined as: severe (any 'A' irrespective of number of 'B' flares), moderate (two or more 'B' without any 'A' flares) and mild (one 'B'). RESULTS: Of the 100 patients, 94% were female, 61% White Caucasians, mean age (s.d.) was 40.7 years (12.7) and mean disease duration (s.d.) was 9.3 years (8.1). A total of 195 flares re-occurred in 76 patients over 781 monthly assessments (flare rate of 0.25/patient-month). There were 37 severe flares, 32 moderate flares and 126 mild flares. By 1 month, 22% had a mild/moderate/severe flare and 22% had a severe flare by 7 months. The median time to any 'A' or 'B' flare was 4 months. Severe/moderate flares tended to be in the system(s) affected at baseline, whereas mild flares could affect any system. CONCLUSION: . In a population with active SLE we observed an ongoing rate of flares from early in the follow-up period with moderate-severe flares being due to an inability to fully control the disease. This real-world population study demonstrates the limitations of current treatments and provides a useful reference population from which to inform future clinical trial design.

Short-term efficacy and safety of rituximab therapy in refractory systemic lupus erythematosus: results from the British Isles Lupus Assessment Group Biologics Register.

Objectives: To describe the baseline characteristics of SLE patients requiring biologic therapy in the UK and to explore short term efficacy and infection rates associated with rituximab (RTX) use. Methods: Patients commencing biologic therapy for refractory SLE and who consented to join BILAG-BR were analysed. Baseline characteristics, disease activity (BILAG 2004/SLEDAI-2K) and rates of infection over follow-up were analysed. Response was defined as loss of all A and B BILAG scores to ⩽ 1 B score with no new A/B scores in other organ systems at 6 months. Results: Two hundred and seventy SLE patients commenced biologic therapy from September 2010 to September 2015, most commonly RTX (n = 261). Two hundred and fifty (93%) patients were taking glucocorticoids at baseline at a median [interquartile range (IQR)] oral dose of 10 mg (5-20 mg) daily. Response rates at 6 months were available for 68% of patients. The median (IQR) BILAG score was 15 (10-23) at baseline and 3 (2-12) at 6 months (P < 0.0001). The median (IQR) SLEDAI-2K reduced from 8 (5-12) to 4 (0-7) (P < 0.001). Response was achieved in 49% of patients. There was also a reduction in glucocorticoid use to a median (IQR) dose of 7.5 mg (5-12 mg) at 6 months (P < 0.001). Serious infections occurred in 26 (10%) patients, being more frequent in the first 3 months post-RTX therapy. A higher proportion of early infections were non-respiratory (odds ratio = 1.98, 95% CI: 0.99, 3.9; P = 0.049). Conclusion: RTX is safe and is associated with improvement in disease activity in refractory SLE patients with concomitant reductions in glucocorticoid use. Early vigilance for infection post-infusion is important to further improve treatment risks and benefits.

An Investigation into the Scale and Impact of Self-Reported Foot Problems Associated with Systemic Lupus Erythematosus: A Study Protocol and Survey Questionnaire Development.

BACKGROUND: Systemic lupus erythematosus (SLE) can manifest with arthralgia and myalgia, and, in severe cases, disorganization of the joints and tendon rupture. Further, Raynaud's phenomenon and other circulatory problems such as vasculitis have been reported, and may be associated with loss of sensation and ulcers. Associated with impaired peripheral neurovascular function there is the potential for changes in tissue viability leading to thinning of the skin or callus formation. In addition, resistance to infections may be reduced, such as fungal infection of the skin and nails, bacterial infection associated with wounds and viral infections such as verruca. There is a dearth of evidence for the effects of SLE in the foot, the prevalence of foot problems in SLE and the impact of these on the individual. In addition, it is not known if people with SLE and foot problems have access to specialist care through foot health services. Hence, there is a need to investigate the scale of foot problems associated with SLE. In order to achieve this, a questionnaire needs to be developed in order to carry out a national survey in England. METHODS: The items required for the questionnaire were generated using a focus group, which comprised patient advisers with SLE, consultants who specialized in SLE, specialist rheumatology podiatrists and specialist rheumatology nurses. From this consensus approach to the item generation, the draft questionnaire was developed with agreement on themes, question format and overall structure. Additionally, the Manchester Pain and Disability Questionnaire was included in order to capture levels of pain and associated disability. An iterative process followed, with feedback from the focus group reducing the number of other items from 53, until the penultimate version of questionnaire was produced with 50 items. Following on from this, a process of cognitive debriefing was used with two people with SLE who were naïve to the questionnaire. Minor changes to two questions and the layout was required before a final version of the questionnaire was produced. DISCUSSION: The questionnaire will be used for a study which aims to identify the frequency of patients' self-reported foot problems, the impact of foot problems on their lives and the status of foot care provision. This will be achieved through a survey of people with SLE across six clinical sites and interviews with some people in order to explore their experience of foot problems. The results from the present study will provide the information required to inform further research. In addition, it could potentially inform the design and delivery of foot health information and services to this patient group. Copyright © 2015 John Wiley & Sons, Ltd.

Sensitivity to Change and Minimal Important Differences of the LupusQoL in Patients With Systemic Lupus Erythematosus.

OBJECTIVE: As a health-related quality of life (HRQOL) measure, the LupusQoL is a reliable and valid measure for adults with systemic lupus erythematosus (SLE). This study evaluates the responsiveness and minimal important differences (MIDs) for the 8 LupusQoL domains. METHODS: Patients experiencing a flare were recruited from 9 UK centers. At each of the 10 monthly visits, HRQOL (LupusQoL, Short Form 36 health survey [SF-36]), global rating of change (GRC), and disease activity using the British Isles Lupus Assessment Group 2004 index were assessed. The responsiveness of the LupusQoL and the SF-36 was evaluated primarily when patients reported an improvement or deterioration on the GRC scale and additionally with changes in physician-reported disease activity. MIDs were estimated as mean changes when minimal change was reported on the GRC scale. RESULTS: A total of 101 patients were recruited. For all LupusQoL domains, mean HRQOL worsened when patients reported deterioration and improved when patients reported an improvement in GRC; SF-36 domains showed comparable responsiveness. Improvement in some domains of the LupusQoL/SF-36 was observed with a decrease in disease activity, but when disease activity worsened, there was no significant change. LupusQoL MID estimates for deterioration ranged from -2.4 to -8.7, and for improvement from 3.5 to 7.3; for the SF-36, the same MID estimates were -2.0 to -11.1 and 2.8 to 10.9, respectively. CONCLUSION: All LupusQoL domains are sensitive to change with patient-reported deterioration or improvement in health status. For disease activity, some LupusQoL domains showed responsiveness when there was improvement but none for deterioration. LupusQoL items were derived from SLE patients and provide the advantage of disease-specific domains, important to the patients, not captured by the SF-36.

Mapping the disease-specific LupusQoL to the SF-6D.

PURPOSE: To derive a mapping algorithm to predict SF-6D utility scores from the non-preference-based LupusQoL and test the performance of the developed algorithm on a separate independent validation data set. METHOD: LupusQoL and SF-6D data were collected from 320 patients with systemic lupus erythematosus (SLE) attending routine rheumatology outpatient appointments at seven centres in the UK. Ordinary least squares (OLS) regression was used to estimate models of increasing complexity in order to predict individuals' SF-6D utility scores from their responses to the LupusQoL questionnaire. Model performance was judged on predictive ability through the size and pattern of prediction errors generated. The performance of the selected model was externally validated on an independent data set containing 113 female SLE patients who had again completed both the LupusQoL and SF-36 questionnaires. RESULTS: Four of the eight LupusQoL domains (physical health, pain, emotional health, and fatigue) were selected as dependent variables in the final model. Overall model fit was good, with R(2) 0.7219, MAE 0.0557, and RMSE 0.0706 when applied to the estimation data set, and R(2) 0.7431, MAE 0.0528, and RMSE 0.0663 when applied to the validation sample. CONCLUSION: This study provides a method by which health state utility values can be estimated from patient responses to the non-preference-based LupusQoL, generalisable beyond the data set upon which it was estimated. Despite concerns over the use of OLS to develop mapping algorithms, we find this method to be suitable in this case due to the normality of the SF-6D data.

Suppression of inflammation reduces endothelial microparticles in active systemic lupus erythematosus.

BACKGROUND: In a prospective observational study, we investigated whether patients with active systemic lupus erythematosus (SLE) had higher indices of endothelial damage and dysfunction than healthy controls and whether improved disease control was associated with improvement in these indices. METHODS: Twenty-seven patients with active SLE (four or more American College of Rheumatology (ACR) criteria) and 22 age-matched controls were assessed. Endothelial microparticles (EMPs; CD31+/annexin V+/CD42b-) were quantified using flow cytometry. Brachial artery flow-mediated dilatation (FMD) was measured using automated edge-tracking software. Twenty-two patients had a second assessment at a median (IQR) of 20 (16, 22) weeks after initiating new immunosuppressive therapy. RESULTS: SLE patients had a median (IQR) baseline global British Isles Lupus Assessment Group Disease Activity Index (BILAG-2004) score of 14 (12, 22). CD31+/annexin V+/CD42b- EMPs were higher (157 548/ml (59 906, 272 643) vs 41 025(30 179, 98 082); p=0.003) and endothelial-dependent FMD was lower (1.63% (-1.22, 5.32) vs 5.40% (3.02, 8.57); p=0.05) in SLE patients than controls. CD31+/annexin V+/CD42b- EMPs correlated inversely with FMD (%) (r(2) -0.40; p=0.006). At follow-up, the median (IQR) change in global BILAG-2004 score was -11 (-18, -3). CD31+/annexin V+/CD42b- EMP levels were reduced (166 982/ml (59 906, 278 775 vs 55 655(29 475, 188 659; p=0.02) and FMD had improved (0.33% (-2.31, 4.1) vs 3.19% (0.98, 5.09); p=0.1) at the second visit. CONCLUSIONS: Active SLE is associated with evidence of increased endothelial damage and endothelial dysfunction, which improved with suppression of inflammation. Better control of active inflammatory disease may contribute to improved cardiovascular risk in patients with SLE.

Shortened telomere length in patients with systemic lupus erythematosus.

OBJECTIVE: Patients with systemic lupus erythematosus (SLE) have a higher rate of premature death compared to the general population, suggesting a phenotype of premature senescence in SLE. Telomere length can be used to assess overall biologic aging. This study was undertaken to address the hypothesis that patients with SLE have reduced telomere length. METHODS: Telomere length was measured cross-sectionally in whole blood from SLE patients and age-matched healthy female controls, using real-time quantitative polymerase chain reaction. SLE-related and cardiovascular risk factors were assessed. RESULTS: We compared telomere length in 63 SLE patients and 63 matched controls with a median age of 50.8 years (interquartile range [IQR] 37-59 years) and 49.9 years (IQR 32-60 years), respectively. The median relative telomere length in SLE patients was 0.97 (IQR 0.47-1.57), compared to 1.53 (IQR 0.82-2.29) in controls (P = 0.0008). We then extended our cohort to measure telomere length in 164 SLE patients. Shorter telomere length was associated with Ro antibodies (ß ± SE -0.36 ± 0.16; P = 0.023), and longer telomere length was associated with steroid therapy (0.29 ± 0.14; P = 0.046). We also noted an association of longer telomere length with increasing body mass index (ß ± SE 0.07 ± 0.01; P < 0.0001) and tobacco smoking (0.64 ± 0.26; P = 0.016), as well as with the presence of carotid plaque (0.203 ± 0.177; P = 0.032). CONCLUSION: Telomere length is shortened in SLE patients compared to controls and does not appear to be a reflection of disease activity or immune cell turnover. Subsets of patients such as those positive for Ro antibodies may be particularly susceptible to premature biologic aging. The predictive value of telomere length as a biomarker of future risk of damage/mortality in SLE requires longitudinal evaluation.

Comparison of the psychometric properties of health-related quality of life measures used in adults with systemic lupus erythematosus: a review of the literature.

OBJECTIVE: A review of the literature was undertaken to evaluate the development and psychometric properties of health-related quality of life (HRQoL) measures used in adults with SLE. This information will help clinicians make an informed choice about the measures most appropriate for research and clinical practice. METHODS: Using the key words lupus and quality of life, full original papers in English were identified from six databases: OVID MEDLINE, EMBASE, Allied and Complementary Medicine, Psychinfo, Web of Science and Health and Psychosocial Instruments. Only studies describing the validation of HRQoL measures in adult SLE patients were retrieved. RESULTS: Thirteen papers were relevant; five evaluated generic instruments [QOLS-S (n = 1), EQ-5D/SF-6D (n = 1), SF-36 (n = 3)] and eight evaluated disease-specific measures [L-QOL (n = 1), LupusQoL (UK) (n = 1), LupusQoL (US) (n = 1), SSC (n = 2), SLEQOL (n = 3)]. For the generic measures, there is moderate evidence of good content validity and internal consistency, whereas there is strong evidence for both these psychometric properties in disease-specific measures. There is limited to moderate evidence to support the construct validity and test-retest reliability for the disease-specific measures. Responsiveness and floor/ceiling effects have not been adequately investigated in any of the measures. CONCLUSIONS: Direct comparison of the psychometric properties was difficult because of the different methodologies employed in the development and evaluation of the different HRQoL measures. However, there is supportive evidence that multidimensional disease-specific measures are the most suitable in terms of content and internal reliability for use in studies of adult patients with SLE.

The BILAG-2004 systems tally--a novel way of representing the BILAG-2004 index scores longitudinally.

OBJECTIVE: This was an exploratory analysis to develop a new way of representing BILAG-2004 system scores longitudinally that would be clinically meaningful and easier to analyse in comparison with multiple categorical variables. METHODS: Data from a multicentre longitudinal study of SLE patients (the BILAG-2004 index and therapy collected at every visit) were used. External responsiveness analysis of the index suggested the possibility of using counts of systems with specified transitions in scores as a basis to analyse the system scores. Exploratory analyses with multinomial logistic regression were used to examine the appropriateness of this new method of analysing BILAG-2004 system scores. Receiver operating characteristic (ROC) curve analysis was used to assess the performance of this approach. RESULTS: There were 1414 observations from 347 patients. A novel method was devised based on counts of systems with defined transitions in score (BILAG-2004 systems tally, BST). It has six components (systems with major deterioration, systems with minor deterioration, systems with persistent significant activity, systems with major improvement, systems with minor improvement and systems with persistent minimal or no activity). This was further simplified (simplified BST, sBST) into three components (systems with active/worsening disease, systems with improving disease and systems with persistent minimal or no activity). Both versions had expected associations with change in therapy. ROC curve analyses demonstrated that both versions had similar good performance characteristics (areas under the curve >0.80) in predicting increase in therapy. CONCLUSION: The BST and sBST provide alternative approaches to representing BILAG-2004 disease activity longitudinally. Further validation of their use is required.

Limited end-user knowledge of methotrexate despite patient education: an assessment of rheumatologic preventive practice and effectiveness.

BACKGROUND: Methotrexate (MTX) is a first-line disease-modifying agent and anchor drug for biologic therapy used in rheumatoid arthritis and other inflammatory rheumatic disorders. Adverse effects are a common cause of drug discontinuation and include preventable serious incidents that may result in patient harm or death. OBJECTIVES: The objective of this study was to audit adherence by health professionals to national and international guidelines for patient education and risk reduction in patients prescribed MTX for inflammatory rheumatic diseases. METHODS: A combination of interviews, case record reviews, and self-administered patient knowledge questionnaires with individual patient feedback was used. The setting was the rheumatology outpatient department of a district general hospital. RESULTS: Fifty-one patients participated in the audit. The mean age was 58.6 (SD, 13.1) years and median duration of disease was 3.7 years (interquartile range, 1.7-7.6 years). Nurse-led patient education was documented at baseline for 94.1% of participants. Despite this, only 11.8% of participants recognized the potentially lethal drug-drug interaction with trimethoprim/Septrin (co-trimoxazole), and less than 60.8% recognized possible major adverse effects related to MTX. Although lifestyle implications relating to alcohol consumption and pregnancy/breast-feeding were recognized by the majority, only 52.9% of males were aware of recommendations in relation to conception. Univariable and multivariable analyses identified male sex, not speaking English as a first language, and a longer duration of therapy as predictors of lower levels of patient knowledge. CONCLUSIONS: Despite consistent baseline patient education, end-user knowledge and awareness pertinent to MTX safety are limited. Good-quality written information in the most appropriate language, patient feedback on educational programs, follow-up testing of patient knowledge, and targeted reeducation are recommended to address individual deficiencies in core knowledge.

Construct and criterion validity of the short form-6D utility measure in patients with systemic lupus erythematosus.

OBJECTIVE: Preference-based measures, such as the Short Form-6D (SF-6D), allow quality-adjusted life-years, used in cost-utility evaluations, to be calculated. We investigated the construct and criterion validity of the SF-6D in patients with systemic lupus erythematosus (SLE). METHODS: Female patients with SLE were recruited from outpatient clinics at 2 timepoints, 5 years apart. Cross-sectional correlation of the SF-6D with domains of the disease-specific LupusQol health-related quality of life (HRQOL) measure, the Systemic Lupus International Collaborating Clinics Damage Index (SDI; for damage) and Systemic Lupus Erythematosus Disease Activity Index (SLEDAI; for activity) measures, and patient characteristics was tested. The ability to discriminate between groups defined by smoking status, presence/absence of carotid plaque, depression, and fatigue was tested using the t-test. RESULTS: In total 181 patients were recruited at baseline. The SF-6D correlated moderately to strongly with all domains of the LupusQoL (0.6-0.8) apart from intimate relationships (0.42) and body image (0.34). Correlations of the SF-6D with the demographic and disease-specific measures at baseline were small for the SDI score (-0.23) and age (-0.19) and in the expected direction. The SF-6D did not correlate with disease activity (SLEDAI -0.08). The SF-6D could distinguish those who smoked, had carotid plaque, had depression, and reported fatigue from those who did not, with the largest effect size being for depression (0.75). CONCLUSION: The SF-6D displays construct and criterion validity for use in patients with SLE, but the low correlation with aspects of intimate relationships and body image represents a concern and reinforces the need to collect disease-specific measures of HRQOL alongside generic preference-based instruments.

25-Hydroxyvitamin D deficiency is associated with increased aortic stiffness in patients with systemic lupus erythematosus.

OBJECTIVE: To determine the relationship between serum vitamin D and markers of subclinical cardiovascular disease (CVD) in patients with SLE. METHODS: We recruited SLE patients (≥ 4 ACR 1997 criteria) from outpatient clinics between January 2007 and January 2009. Vitamin D deficiency was defined as serum 25(OH)D <20 ng/ml measured by ELISA. Disease activity was measured using the SLEDAI-2K score. Aortic pulse wave velocity (aPWV) was measured using PulseTrace 3600 (Micromedical) and carotid plaque (CP) and intima-media thickness (IMT) assessed using B-mode Doppler US. RESULTS: Seventy-five women with SLE were recruited with a median (interquartile range) disease duration of 16 (8-27) years. Patients with vitamin D deficiency had higher BMI (P = 0.014) and insulin resistance (P = 0.023) than those with 25(OH)D >20 ng/ml. Subjects with SLEDAI-2K ≥ 4 had lower 25(OH)D than those with SLEDAI-2K <4 (median 12.9 vs 20.3 ng/ml, P = 0.031). Aortic stiffness was significantly associated with serum 25(OH)D [log(aPWV) ß (95% CI) -0.0217 (-0.038, -0.005), P = 0.010] independently of BMI, CVD risk factors and serum insulin. Adjustment for disease activity reduced the strength of the association. There was no association between 25(OH)D and CP or IMT. CONCLUSIONS: Vitamin D deficiency is associated with increased aortic stiffness in SLE, independent of CVD risk factors and insulin. Increased inflammatory disease activity may be the mechanism by which vitamin D deficiency mediates vascular stiffness in this patient group.