Clinical efficacy of oral alendronate in ankylosing spondylitis: a randomised placebo-controlled trial.

OBJECTIVES: A prospective, double blind, randomised, placebo controlled trial over 2 years was performed to test the efficacy of alendronate, an oral aminobisphosphonate, in improving symptoms and arrest disease progression in patients with mild to severe ankylosing spondylitis (AS). METHODS: 180 patients with AS were randomised to receive weekly alendronate 70 mg or placebo (1:1 randomisation). BAS-G was the primary outcome measure with Bath indices as secondary outcomes. Vertebral x-rays were performed at 0 and 24 months. Biomarkers (including CRP, IL-1beta, IL6, VEGF, MMP-1, and MMP-3) were collected during the first 12 months. RESULTS: There was no significant difference between the placebo and treatment groups in any of the recorded outcomes over the 2 years including clinical indices, biomarkers, and radiology. The change in BAS-G, the primary outcome measure, was -0.21 for the treatment group and -0.42 for the placebo group p=0.57. Change in all other clinical outcome measures were also non-significant; BASDAI p=0.86, BASFI p=0.37, BASMI p=0.021. Sub-group analysis of those subjects with a baseline BASDAI >4 were also non-significant. CONCLUSIONS: This prospective study demonstrates that alendronate 70mg weekly for 2 years was no more efficacious than placebo in improving clinical or laboratory measures of disease activity or measures of physical impact in subjects with mild to severe active AS. TRIAL REGISTRATION: ID SRCTN12308164, registered on 15.12.2015.

Assessing fatigue in ankylosing spondylitis: the importance of frequency and severity.

OBJECTIVE: The aim of this study was to explore the value of assessing fatigue frequency and its relationship with fatigue severity in a UK cohort of AS patients. METHODS: Single items from the Evaluation of AS Quality of Life and BASDAI were used to measure fatigue frequency and severity, respectively. Items were included in a questionnaire containing AS-specific and generic measures, completed by participants in a postal survey at baseline and 6 months. Respondents were categorized at baseline into four groups according to fatigue frequency and severity and compared on other measures of health status. RESULTS: Of baseline responders who experienced fatigue (n = 451, 74%), 75% reported it to be frequent and severe, 15% frequent not severe and 10% severe not frequent. There was no difference between groups on gender, age or years with AS. Patients reporting frequent and severe fatigue had worse scores than other groups across all other health status measures. Patients reporting only frequent fatigue had similar scores to those reporting only severe fatigue, but worse than those without fatigue. Eighty-one per cent of non-fatigued patients and 79% of those with frequent and severe fatigue at baseline did not change their level of fatigue at 6 months. However, 80% of patients with frequent or severe fatigue at baseline changed, mainly to no fatigue (43%) or both frequent and severe fatigue (30%). CONCLUSION: Routinely assessing both the frequency and severity of fatigue is important in understanding the impact of fatigue and its change over time. Not assessing frequency could result in the failure to identify patients with significant fatigue. However, the multidimensional nature of fatigue should be further explored.

A randomized placebo-controlled trial of methotrexate in psoriatic arthritis.

OBJECTIVE: MTX is widely used to treat synovitis in PsA without supporting trial evidence. The aim of our study was to test the value of MTX in the first large randomized placebo-controlled trial (RCT) in PsA. METHODS: A 6-month double-blind RCT compared MTX (15 mg/week) with placebo in active PsA. The primary outcome was PsA response criteria (PsARC). Other outcomes included ACR20, DAS-28 and their individual components. Missing data were imputed using multiple imputation methods. Treatments were compared using logistic regression analysis (adjusted for age, sex, disease duration and, where appropriate, individual baseline scores). RESULTS: Four hundred and sixty-two patients were screened and 221 recruited. One hundred and nine patients received MTX and 112 received placebo. Forty-four patients were lost to follow-up (21 MTX, 23 placebo). Twenty-six patients discontinued treatment (14 MTX, 12 placebo). Comparing MTX with placebo in all randomized patients at 6 months showed no significant effect on PsARC [odds ratio (OR) 1.77, 95% CI 0.97, 3.23], ACR20 (OR 2.00, 95% CI 0.65, 6.22) or DAS-28 (OR 1.70, 95% CI 0.90, 3.17). There were also no significant treatment effects on tender and swollen joint counts, ESR, CRP, HAQ and pain. The only benefits of MTX were reductions in patient and assessor global scores and skin scores at 6 months (P = 0.03, P < 0.001 and P = 0.02, respectively). There were no unexpected adverse events. CONCLUSIONS: This trial of active PsA found no evidence for MTX improving synovitis and consequently raises questions about its classification as a disease-modifying drug in PsA. Trial registration. Current Controlled Trials, www.controlled-trials.com, ISRCTN:54376151.

Development of the Warwick Axial Spondyloarthritis faTigue and Energy questionnaire (WASTEd)-a new patient-reported outcome measure.

Objective: The aim was to co-produce and test a potential new patient-reported outcome measure (PROM), the Warwick Axial Spondyloarthritis faTigue and Energy questionnaire (WASTEd), providing vital qualitative confirmation of conceptual relevance, clarity and acceptability. Methods: Informed by measurement theory, we collaborated with patient partners throughout a three-stage, iterative process of PROM development. In stage 1, informed by patient interviews, reviews exploring patients' fatigue experiences and existing PROMs of fatigue, an initial measurement framework of axial spondyloarthritis (axSpA) fatigue and energy and candidate items were defined. In stage 2, the relevance and acceptability of the measurement framework and candidate items were assessed qualitatively by focus group participants. In stage 3, patients participated in pre-testing interviews to assess item comprehensiveness, relevance, acceptability and comprehensibility. Results: Stage 1 informed the development of an initial five-domain measurement framework with 59 candidate items. In stage 2, five patients and seven health-care professionals participated in four focus groups to derive a 40-item model of fatigue and energy. Collaborative engagement with patient research partners supported refinement of questionnaire structure and content further. Pre-testing with ten patients across two interview rounds in stage 3 produced a four-domain, 30-item long-form questionnaire. Conclusion: An active collaboration with patients and health-care professionals has supported the co-production of a potential new PROM of axSpA fatigue, underpinned by strong evidence of face and content validity. The WASTEd extends the assessment of fatigue beyond severity, highlighting the importance of symptom frequency, energy and self-management. Future research will involve psychometric evaluation, supporting item reduction, structural refinement and confirmation of PROM validity.

Qualitative interview study exploring the patient experience of living with axial spondyloarthritis and fatigue: difficult, demanding and draining.

OBJECTIVE: To explore patients' lived experiences of axial spondyloarthritis (axSpA) and fatigue. DESIGN: Interpretative phenomenological analysis (lived experience) was used as the study design. Analysis drew together codes with similar meaning to create superordinate and subordinate themes. SETTING: Rheumatology departments in three National Health Service Foundation Trusts in the north, midlands and south of England. PARTICIPANTS: A purposive sample of seventeen axSpA patients were recruited. The age range was 22-72 years (median age 46), nine were male and eight, female. RESULTS: A central concept of achieving balance was identified as the active process of integrating axSpA symptoms and fatigue into daily life, working with and not against their condition to lead a fulfilled life. This was conveyed through three superordinate themes: struggling to find energy, engaging in everyday life and persevering through difficulties. Struggling to find energy was the challenge of retaining enough stamina to do things in daily life. Engaging in everyday life highlighted dedication to being active and organised, learning through experience and acceptance of a changed way of being. Persevering through difficulties identified the physical and emotional effort required to keep moving forward and the importance of feeling supported. CONCLUSION: Achieving balance through finding energy, engaging and persevering everyday was fundamental to having the best possible life. The experience of energy emerged as a distinct but related component of fatigue. However, while energy could be maintained or replenished, fatigue was more difficult to overcome and required greater effort. Energy may be a useful indicator of an individual's current state and ability to sustain activities that supports their well-being, such as exercise. Awareness of the elements of achieving balance in axSpA may enable patients and clinicians to work together to tailor treatments to individual patient need.

Evaluation and Validation of a Patient-completed Psoriatic Arthritis Flare Questionnaire.

OBJECTIVE: Evaluation of a psoriatic arthritis (PsA), multidimensional, patient-completed disease flare questionnaire (FLARE). METHODS: The FLARE questionnaire was administered to 139 patients in a prospective observational study. The "gold standard" of flare was based on patient opinion. Test-retest reliability was evaluated by intraclass correlation coefficient (ICC). Disease activity was measured by the Psoriatic Arthritis Disease Activity Score (PASDAS), Group for Research and Assessment of Psoriasis and PsA (GRAPPA) Composite Exercise (GRACE), Composite Psoriatic Disease Activity Index (CPDAI), and Disease Activity Index for Psoriatic Arthritis (DAPSA). RESULTS: The most common symptoms of a PsA flare were musculoskeletal, followed by fatigue, frustration, loss of function, and an increase in cutaneous symptoms. The test-retest ICC for the FLARE questionnaire was 0.87 (95% CI 0.72-0.94). The optimum cut-off to identify a flare of disease was 4/10 (sensitivity 0.82, specificity 0.76; area under the curve 0.85). For those patients scoring ≥ 4, the mean score for the composite measures was as follows (score for those not reporting a flare in parentheses): PASDAS 5.3 ± 1.3 (3.1 ± 1.6); GRACE 4.5 ± 1.2 (2.2 ± 1.4); CPDAI 8.9 ± 2.5 (4.7 ± 3.1); and DAPSA 38.2 ± 20.3 (16.8 ± 14.9). In a new flare, the increase in composite measure score was calculated as follows: 1 for PASDAS and GRACE, 2 for CPDAI, and 7 for DAPSA. Agreement between the definition of flare using the cut-off of 4 from the questionnaire, and that indicated by the subject in a separate, standalone question was 0.57 (Cohen κ). CONCLUSION: A PsA flare displays escalation of symptoms and signs across multiple domains. The FLARE questionnaire has external validity in terms of both composite disease activity and overall patient opinion about the state of their condition.

Increased Risk of Hypertension Associated with Spondyloarthritis Disease Duration: Results from the ASAS-COMOSPA Study.

OBJECTIVE: Spondyloarthritis (SpA) is associated with a number of cardiovascular (CV) comorbidities. We examined the association of SpA disease duration and delay in diagnosis with CV-related conditions. METHODS: Using data from the COMOSPA study, the associations between SpA disease duration and CV-related conditions were evaluated in univariable and multivariable logistic regression models. Each model examined 1 CV-related factor as dependent and "SpA disease duration" as a predictor, adjusted for relevant confounders. RESULTS: Data from 3923 subjects (median SpA disease duration 5.1 yrs, interquartile range 1.3-11.8 yrs) were available for analysis. The main CV-related conditions were hypertension (HTN; 22.4%), ischemic heart disease (2.6%), stroke (1.3%), and diabetes mellitus (5.5%). HTN was associated with SpA disease duration in both univariable and multivariable analysis, with an OR of 1.129 (95% CI 1.072-1.189; p < 0.001) for each 5-year increase in SpA disease duration. Other factors associated with HTN were age, male sex, current body mass index, ever steroid therapy, and ever synthetic disease-modifying antirheumatic drug therapy, but not nonsteroidal antiinflammatory drugs (NSAID). In subgroup analysis, the strongest association of HTN and disease duration was seen in subjects with the axial-only SpA phenotype (OR 1.202, 95% CI 1.053-1.372) but not in those with peripheral-only SpA (OR 0.902, 95% CI 0.760-1.070). The other CV conditions were not associated with SpA disease duration. CONCLUSION: Duration of SpA disease in the ASAS-COMOSPA cohort is associated with higher odds of HTN, particularly in those with axial disease, but not with other CV-related conditions. The association with HTN does not appear to be related to NSAID exposure.

Assessing fatigue in adults with axial spondyloarthritis: a systematic review of the quality and acceptability of patient-reported outcome measures.

OBJECTIVE: The aim was to evaluate the quality and acceptability of patient-reported outcome measures used to assess fatigue in patients with axial spondyloarthritis. METHODS: A two-stage systematic review of major electronic databases (1980-2017) was carried out to: (i) identify measures; and (ii) identify evaluative studies. Study and measurement quality were evaluated following international standards. Measurement content was appraised against a conceptual model of RA-fatigue. RESULTS: From 387 reviewed abstracts, 23 articles provided evidence for nine fatigue-specific measures: 6 multi-item and 3 single-item. No axial spondyloarthritis-fatigue-specific measure was identified. Evidence of reliability was limited, but acceptable for the Multi-dimensional Fatigue Inventory (internal consistency, test-retest) and Short Form 36-item Health Survey Vitality subscale (SF-36 VT; internal consistency). Evidence of construct validity was moderate for the Functional Assessment of Chronic Illness Therapy-Fatigue and 10 cm visual analog scale, limited for the SF-36 VT and not available for the remaining measures. Responsiveness was rarely evaluated. Evidence of measurement error, content validity or structural validity was not identified. Most measures provide a limited reflection of fatigue; the most comprehensive were the Multi-dimensional Assessment of Fatigue, Multi-dimensional Fatigue Inventory-20, Functional Assessment of Chronic Illness Therapy-fatigue and Fatigue Severity Scale. CONCLUSION: The limited content and often poor quality of the reviewed measures limit any clear recommendation for fatigue assessment in this population; assessments should be applied with caution until further robust evidence is established. Well-developed, patient-derived measures can provide essential evidence of the patient's perspective to inform clinical research and drive tailored health care. The collaborative engagement of key stakeholders must seek to ensure that future fatigue assessment is relevant, acceptable and of high quality.

Quality and acceptability of patient-reported outcome measures used to assess fatigue in axial spondyloarthritis (axSpA): a systematic review (protocol).

BACKGROUND: The prevalence of axial spondyloarthritis (axSpA) is estimated between 0.15 and 1.2%, with many of those patients experiencing severe fatigue. Current axSpA assessment guidance recommends use of a single-item visual analogue scale for fatigue severity. However, concerns have been raised about the ability of such a limited assessment to identify patients with major fatigue, to detect important change in fatigue or to reflect the multi-dimensional nature of fatigue. The proposed systematic review will identify and evaluate the quality and acceptability of single- and multi-item patient-reported outcome measures (PROMs) used to assess fatigue in axSpA, seeking to make recommendations for the 'best' measures for research and/or clinical practice. METHODS/DESIGN: The review will seek to include published studies which report evidence of the development and/or measurement and/or practical properties of clearly defined and reproducible measures of fatigue following completion by patients with axSpA. Five major databases will be searched from 1980 to August 2017: MEDLINE (OVID), EMBASE (OVID), PsycINFO (OVID), World of Science and CINAHL. Study methodological quality will be assessed against the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) checklist. The measurement and/or practical properties of reviewed measures will be assessed against current international standards. A short list of the 'best'-quality PROMs will be produced. The review will be reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. DISCUSSION: This study will provide the first robust and transparent evaluation of patient-reported measures of fatigue used in the axSpA population, synthesising evidence of quality, relevance and acceptability. The review will benefit patients, clinicians, health professionals and researchers wishing to enhance axSpA-fatigue assessment in routine practice, service evaluation and research. The findings will impact future research which seeks to better understand the nature of axSpA fatigue and evaluate the relative benefit of fatigue-management strategies. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42016042271.

Influence of adult height on rheumatoid arthritis: association with disease activity, impairment of joint function and overall disability.

OBJECTIVES: To investigate whether normal variation of adult height is associated with clinical characteristics in rheumatoid arthritis (RA), including disease activity (DAS28), impairment of joint function (mechanical joint score, MJS) and overall disability (health assessment questionnaire, HAQ). METHODS: A cohort (134 males, 287 females) of consecutively recruited RA patients of Northern European origin was studied. Height, weight and demographic information were obtained. A core set of disease measurements, including DAS28, MJS and HAQ, were recorded at baseline, 12 and 24 months. Other clinical variables (e.g. disease duration, IgM rheumatoid factor, antibodies to cyclic citrullinated peptide, C-reactive protein, erythrocyte sedimentation rate) were recorded at baseline. Socioeconomic status, smoking status, comorbid condition, other autoimmune conditions and drug therapy were also recorded. Associations were analyzed using univariate statistics and multivariate linear regression models. Mediation tests were also carried out for evaluating the relationship between gender, height and disease measures. RESULTS: In males, height was inversely associated with DAS28, MJS and HAQ (at baseline and over 24 months) independent of other factors (e.g. weight, body mass index, age, disease duration, osteoporosis, autoantibodies, erosive disease, joint replacement, steroid use, smoking status, socioeconomic status and comorbid disease). In females, a similar trend was seen but the relationships were non significant. In the whole population, the association of female gender with more active disease and poor function disappeared after adjustment for height. Mediation analysis indicated that height served as a full mediator in the relationship of gender with disease activity and overall disability. Confirmation of these findings was demonstrated in a second RA population (n = 288). CONCLUSION: Adult height is inversely associated with disease activity, impairment of joint function and overall disability in RA, particularly in males. The association of female sex with more severe disease activity and disability appears to be mediated by smaller stature.

Association of cytokine and matrix metalloproteinase profiles with disease activity and function in ankylosing spondylitis.

INTRODUCTION: The pathology of ankylosing spondylitis (AS) suggests that certain cytokines and matrix metalloproteinases (MMPs) might provide useful markers of disease activity. Serum levels of some cytokines and MMPs have been found to be elevated in active disease, but there is a general lack of information about biomarker profiles in AS and how these are related to disease activity and function. The purpose of this study was to investigate whether clinical measures of disease activity and function in AS are associated with particular profiles of circulating cytokines and MMPs. METHODS: Measurement of 30 cytokines, five MMPs and four tissue inhibitors of metalloproteinases was carried out using Luminex® technology on a well-characterised population of AS patients (n = 157). The relationship between biomarker levels and measures of disease activity (Bath ankylosing spondylitis disease activity index (BASDAI)), function (Bath ankylosing spondylitis functional index) and global health (Bath ankylosing spondylitis global health) was investigated. Principal component analysis was used to reduce the large number of biomarkers to a smaller set of independent components, which were investigated for their association with clinical measures. Further analyses were carried out using hierarchical clustering, multiple regression or multivariate logistic regression. RESULTS: Principal component analysis identified eight clusters consisting of various combinations of cytokines and MMPs. The strongest association with the BASDAI was found with a component consisting of MMP-8, MMP-9, hepatocyte growth factor and CXCL8, and was independent of C-reactive protein levels. This component was also associated with current smoking. Hierarchical clustering revealed two distinct patient clusters that could be separated on the basis of MMP levels. The high MMP cluster was associated with increased C-reactive protein, the BASDAI and the Bath ankylosing spondylitis functional index. CONCLUSIONS: A profile consisting of high levels of MMP-8, MMP-9, hepatocyte growth factor and CXCL8 is associated with increased disease activity in AS. High MMP levels are also associated with smoking and worse function in AS.

Relationship between smoking and patient-reported measures of disease outcome in ankylosing spondylitis.

OBJECTIVE: To investigate the relationship between smoking and disease activity, pain, function, and quality of life in patients with ankylosing spondylitis (AS). METHODS: Patients with AS (n = 612) from areas across the United Kingdom took part in a cross-sectional postal survey. Patient-reported outcome measures including the Bath AS Disease Activity Index, the Bath AS Functional Index (BASFI), a numerical rating scale (NRS) of pain, the AS quality of life questionnaire (ASQoL), and the evaluation of AS quality of life measures (EASi-QoL) were analyzed in terms of smoking status and relationship with pack-year history. The influence of potential confounding factors [age, sex, disease duration, and social deprivation (Townsend Index)] were tested in multivariate logistic regression analyses. RESULTS: Median scores of BASFI, pain NRS, ASQoL, and the 4 EASi-QoL domains were all higher in the group that had ever smoked compared to those who had never smoked (p < 0.0001, p = 0.04, p = 0.003, p < 0.02, respectively). In stepwise multivariate logistic regression analyses, high disease activity and more severe pain were associated primarily with current smoking, disease duration, and Townsend Index score, while decreased function and poor quality of life measures were associated more closely with increasing pack-year history, disease duration, and Townsend Index score. These associations were independent of age and sex. CONCLUSION: Smoking has a dose-dependent relationship with measures of disease severity in AS. The association with increased disease activity, decreased function, and poor quality of life in smokers was independent of age, sex, deprivation level, and disease duration.

Interaction between smoking and polymorphism in the promoter region of the VEGFA gene is associated with ischemic heart disease and myocardial infarction in rheumatoid arthritis.

OBJECTIVE: To determine whether variants in the vascular endothelial growth factor A (VEGFA) gene are associated with ischemic heart disease (IHD) and/or myocardial infarction (MI) in patients with rheumatoid arthritis (RA), and whether there is evidence of a gene-smoking interaction. METHODS: PCR-RFLP assays were used to determine the genotypes of VEGFA single-nucleotide polymorphisms (SNP) including VEGFA-2578A/C (rs699947), -460C/T (rs833061), +405C/G (rs2010963), and +936C/T (rs3025039) in 418 subjects with RA. Smoking history was obtained on each patient, and IHD and MI status was recorded. Associations with IHD/MI were assessed using contingency tables and logistic regression analyses. RESULTS: Strong linkage disequilibrium was detected among VEGFA-2578, -460, and +405. SNP located in the VEGFA promoter region (-2578, -460) were found to be associated with IHD and MI, whereas +405 and +936, in the 5'-untranslated region (UTR) and 3'-UTR, respectively, were not. Haplotype analysis suggested that the A/C/G haplotype was associated with increased risk of IHD (OR 2.37, 95% CI 1.22-4.62) and MI (OR 4.10, 95% CI 1.45-11.49). Smoking was also independently associated with IHD and MI, and evidence of interaction between smoking and the VEGFA promoter SNP was found. Multivariate analyses indicated that the strongest associations with IHD and MI were due to the combined effect of the VEGFA-2578 A allele and smoking (OR 3.52 and 7.11, respectively), independent of risk factors such as age, sex, diabetes, C-reactive protein, hypercholesterolemia, and hypertension. CONCLUSION: Interaction between smoking and polymorphism in the VEGFA gene is associated with IHD and MI in patients with RA.

Disease severity in ankylosing spondylitis: variation by region and local area deprivation.

OBJECTIVE: To investigate whether patient disease severity in ankylosing spondylitis (AS) varies among regions or by local area social deprivation. METHODS: Eight hundred patients with AS from 8 specialist rheumatology centers across England were invited to participate in a cross-sectional survey. Sociodemographic and disease-related variables were collected [pain (numerical rating scale), disease activity (Bath AS Disease Activity Index), and physical function (Bath AS Functional Index)]. Deprivation was measured using the Index of Multiple Deprivation 2004. RESULTS: Of the 800 patients invited, 468 responded (adjusted response rate 62.8%). Most were male (72.9%), with a mean age of 50.2 years (SD 12.1), and a mean diagnosed disease duration of 17 years (SD 11.4). Across all centers, those living in more deprived areas demonstrated significantly greater disease severity and poorer psychological health. After controlling for age, gender, disease duration, and region, greater deprivation was significantly associated with greater disease activity (OR 3.39; 95% CI 1.65, 6.98) and poorer function (OR 4.46; 95% CI 2.11, 9.44). There was a nonsignificant trend toward more pain (OR 1.98; 95% CI 0.97, 4.07). There was also a significant independent association between region and disease severity. CONCLUSION: The need for healthcare is greatest for patients with AS who are living in more socially deprived areas. With the growing use of interventional therapies, these findings have important implications if health service resources are to be allocated equitably; particularly as deprived patients are known to access healthcare less frequently.

Evaluation of ankylosing spondylitis quality of life (EASi-QoL): reliability and validity of a new patient-reported outcome measure.

OBJECTIVE: There is currently no universally accepted measure of quality of life in ankylosing spondylitis (AS). Our objective was to develop and evaluate a patient-reported outcome measure of quality of life in AS, EASi-QoL. METHODS: We used patient interviews, a literature review, and completion of an individualized measure of AS quality of life during clinic-based and pilot surveys to derive questionnaire content. Classical and modern psychometrics were then used to evaluate the questionnaire using data from a large UK-based postal survey of 1000 patients with AS. RESULTS: Data analysis from the interviews and clinic-based and postal surveys produced a 57-item self-completed questionnaire. Fifteen items were removed as a result of patient interviews and the pilot survey. In total, 612 (64.0%) patients responded to the main postal survey. After assessment of data quality, confirmatory factor analysis, and Rasch analysis, 20 items were found to contribute to 4 domains of AS-related quality of life: physical function, disease activity, emotional well-being, and social participation. Item-total correlations ranged from 0.66 to 0.84. Cronbach's alpha and test-retest reliability estimates were 0.88-0.92 and 0.88-0.93, respectively. Confirmed hypothesized correlations with the AS Quality of Life questionnaire, the Bath AS Disease Activity Index, Bath AS Functional Index, SF-36, EQ-5D, and the Hospital Anxiety and Depression Scale were evidence for the construct validity of the EASi-QoL. CONCLUSION: The EASi-QoL has good evidence of data quality, internal reliability, test-retest reliability, and content and construct validity, and should be considered for use with patients in routine practice settings and in evaluative studies including clinical trials. Measurement responsiveness and minimal important change are currently being assessed.

Effect of psychological distress on continuation of anti-tumor necrosis factor therapy in patients with rheumatoid arthritis.

OBJECTIVE: To investigate the relationship of psychological distress and associated factors with continuation of tumor necrosis factor (TNF) antagonist therapy in patients with rheumatoid arthritis (RA). METHODS: Patients about to start therapy with TNF antagonists (n = 166) were assessed for psychological distress using the Hospital Anxiety and Depression Scale (HADS). A core set of demographic and clinical variables, including comorbidities from medical records and cigarette smoking history by questionnaire, were recorded at baseline and regular intervals thereafter. Cox proportional hazards regression analysis was used to assess the likelihood of patients discontinuing therapy over a 36-month followup period. RESULTS: The number of years smoked was associated with anxiety (HADS-A; p for trend = 0.008) and general psychological distress (HADS-Total; p for trend = 0.03). In univariate analyses, earlier discontinuation was associated with these variables at baseline: anxiety (HADS-A), depression (HADS-D), abnormal mood (HADS-Total), smoking history (> 30 pack-yrs), years smoked (> 30 yrs), current smoking, high Disease Activity Score 28-joint count (DAS28), poor patient global assessment, and evidence of cardio/cerebrovascular disease (CVD). In multivariate analyses, the strongest predictors of discontinuation were HADS-Total, smoking history (> 30 pack-yrs), DAS28, and evidence of CVD at baseline. CONCLUSION: Discontinuation of therapy with TNF antagonists is independently associated with psychological distress, heavy smoking, and CVD at baseline.