Inflammatory Bowel Disease Risk in Patients With Axial Spondyloarthritis Treated With Biologic Agents Determined Using the BSRBR-AS and a MetaAnalysis.

OBJECTIVE: To determine, among patients with axial spondyloarthritis (axSpA), whether the risk of inflammatory bowel disease (IBD) varies between patients treated with biologic therapies and those treated with other therapies and, specifically, whether the risk is higher in patients treated with etanercept (ETN). METHODS: The British Society for Rheumatology Biologics Register in Ankylosing Spondylitis (BSRBR-AS) was used to determine the incidence of IBD during follow-up and to calculate the incidence rate difference (IRD) per 1000 person-years (PY), between biologic treatment and other treatment groups. We then conducted a systematic review, involving observational studies and randomized controlled trials (RCTs), to perform a metaanalysis to quantify the difference in incidence of IBD between treatment groups. RESULTS: According to the BSRBR-AS, among people with axSpA, exposure to biologic therapy was associated with an increased incidence of IBD compared to those who were not exposed to biologic therapy (IRD 11.9, 95% CI 4.3-19.6). This finding was replicated across observational studies but was not seen in placebo-controlled RCTs (IRD 2.2, 95% CI -4.1 to 8.5). Data from the BSRBR-AS do not suggest that excess incidence of IBD is associated with exposure to ETN compared to other anti-tumor necrosis factor (TNF) therapies (IRD -6.5, 95% CI -21.3 to 8.5). RCTs and their extensions suggest a small-yet not statistically significant-absolute increased incidence associated with ETN of between 2.1 and 5.8 per 1000 PY compared to other anti-TNF therapies. CONCLUSION: There was an excess risk of IBD among persons treated with biologics in observational studies. Only evidence from RCTs suggested that ETN was associated with an increased risk compared to other anti-TNF therapies, albeit with considerable uncertainty.

Role of Metrology in Axial Spondyloarthritis: Does It Provide Unique Information in Assessing Patients and Predicting Outcome? Results From the British Society for Rheumatology Biologic Register for Ankylosing Spondylitis.

OBJECTIVE: To determine among patients with axial spondyloarthritis (SpA) the factors associated with decreased spinal mobility and to determine whether poor mobility is a predictor of response to anti-tumor necrosis factor (anti-TNF) therapy. METHODS: This was a prospective UK cohort study of persons meeting Assessment of Spondylarthritis international Society (ASAS) criteria for axial SpA. At recruitment, clinical and patient-reported factors independently associated with spinal mobility (measured by the Bath Ankylosing Spondylitis Metrology Index [BASMI]) were determined. Among those commencing anti-TNF therapy, factors that were independent predictors of response were determined using ASAS criteria, quality of life, and Ankylosing Spondylitis Disease Activity Score (ASDAS) response criteria. RESULTS: A total of 1,960 participants were eligible; 70% were male, the median age was 48 years (interquartile range [IQR] 37, 59), and the median BASMI score 3.6 (IQR 2.2, 5.3). Factors independently associated with poor spinal mobility were poorer function, meeting radiographic criteria for AS, longer symptom duration, higher levels of inflammation (measured by C-reactive protein level), older age, male sex, not being currently employed, and lower levels of education. For 51% of participants, the measured BASMI score was within 1 of that estimated. Poorer mobility (higher BASMI score) was an independent predictor of not meeting response criteria for ASAS 20% improvement (odds ratio [OR] per increasing score 0.80 [IQR 0.66, 0.98]), ASAS 40% improvement (OR 0.69 [IQR 0.50, 0.95]), and quality of life (measured by the Ankylosing Spondylitis Quality of Life Questionnaire) (ß = 0.64 [IQR 0.26, 1.02]), but was not related to meeting ASDAS response criteria. CONCLUSION: The BASMI score was estimated moderately well by other routinely measured factors in patients with axial SpA and was an independent predictor of response to biologic therapy for some, but not all, commonly used measures. Consensus around its role in disease monitoring and clinical decisions, particularly in the likely context of face-to-face consultations becoming less frequent, remains to be established.

The changing states of fibromyalgia in patients with axial spondyloarthritis: results from the British Society of Rheumatology Biologics Register for Ankylosing Spondylitis.

OBJECTIVES: To identify factors associated with FM development and recovery in patients with axial SpA (axSpA). METHODS: The British Society of Rheumatology Biologics Register for Ankylosing Spondylitis (BSRBR-AS) recruited patients with axSpA from 83 centres in a prospective study. FM was diagnosed using the self-reported Fibromyalgia Survey Diagnostic Criteria from 2015. Measures of axSpA disease activity and clinical findings were recorded at regular intervals. We identified predictors for FM development and recovery between yearly visits using uni- and multivariable logistic regression models. RESULTS: A total of 801 participants, 247 (30.8%) female, had two or more visits and were eligible for inclusion. A total of 686 participants did not have FM at baseline, of whom 45 had developed FM at follow-up, while 115 participants had FM at baseline, of whom 77 had recovered at follow-up. A high baseline BASDAI score [odds ratio (OR) 1.27 (95% CI 1.08, 1.49)] and Widespread Pain Index (WPI) [OR 1.14 (95% CI 1.02, 1.28)] were significantly associated with FM development in the final multivariable model. A low baseline BASFI score [OR 0.68 (95% CI 0.53, 0.86)] and WPI [OR 0.84 (95% CI 0.720, 0.97)] and starting a TNF inhibitor [OR 3.86 (95% CI 1.54, 9.71)] were significantly associated with FM recovery. CONCLUSION: High levels of disease activity and the presence of widespread pain is associated with the development of FM in patients with axSpA, while low levels of the same variables and starting a TNF inhibitor are associated with recovery from FM. The presence of comorbid FM should be considered in patients with persistent high axSpA disease activity and widespread pain.

Feasibility, acceptability and change in health following a telephone-based cognitive behaviour therapy intervention for patients with axial spondyloarthritis.

OBJECTIVE: The aim was to assess the feasibility and acceptability of a telephone-based cognitive behaviour therapy (tCBT) intervention for individuals with axial SpA (axSpA), with and without co-morbid FM, and to measure the change in patient-reported health outcomes. METHODS: A convenience sample of individuals recruited from British Society for Rheumatology Biologics Registry for AS (BSRBR-AS) sites were offered a course of tCBT (framed as coaching). Patient-reported outcomes were measured at baseline and on course completion. Semi-structured qualitative interviews assessed intervention acceptability. Thematic analysis was informed by the theoretical framework of acceptability. RESULTS: Forty-two participants attended for initial assessment. Those completing at least one tCBT session (n = 28) were younger, more likely to meet classification criteria for FM (57 vs 29%) and reported higher disease activity. Modest improvements were reported across a range of disease activity and wider health measures, with 62% of patients self-rating their health as improved (median 13 weeks post-intervention). Twenty-six participants were interviewed (including six who discontinued after initial assessment). tCBT was widely acceptable, offering a personalized approach. Despite low or unclear expectations, participants described improved sleep and psychological well-being and gained new skills to support self-management. Reasons for non-uptake of tCBT centred on lack of perceived need and fit with individual value systems. Many felt that tCBT would be most useful closer to diagnosis. CONCLUSION: Higher uptake among axSpA patients with co-morbid FM suggests that these individuals have additional needs. The findings are helpful in identifying patients most likely to engage with and benefit from tCBT and to maximize participation.

Similar biologic drug response regardless of radiographic status in axial spondyloarthritis: data from the British Society for Rheumatology Biologics Register in Ankylosing Spondylitis registry.

OBJECTIVE: To describe the baseline characteristics, biologic DMARD (bDMARD) response and drug survival of axial SpA (axSpA) patients in the British Society for Rheumatology Biologics Register in Ankylosing Spondylitis (BSRBR-AS) according to radiographic status. METHODS: The BSRBR-AS is a national prospective cohort including axSpA participants classified according to the Assessment of SpondyloArthritis international Society criteria. In this analysis, baseline data of patients starting bDMARDs were compared. Ankylosing Spondylitis Disease Activity Scores (ASDASs) for low disease status, clinically important improvement (CII) and major improvement (MI) at 1 year were used to assess treatment response. Cox proportional hazards analysis was performed after adjusting for clinically relevant confounders. RESULTS: A total of 1145 axSpA patients were included. Higher male prevalence, older age and longer disease duration were seen in the radiographic axSpA (r-axSpA) subgroup. Based on a complete case analysis (290 patients), two-thirds of patients achieved an ASDAS low disease state at 1 year regardless of radiographic status [non-radiographic axSpA (nr-axSpA) 64.2% vs r-axSpA 66.1]. No statistically significant differences were seen between the subgroups in attaining ASDAS CII (nr-axSpA 50.7% vs r-axSpA 44.7%) or MI (nr-axSpA 20% vs r-axSpA 18.7%). Drug survival probability curves were similar for both subgroups and the hazard ratio for nr-axSpA/axSpA was 0.94 (95% CI 0.69, 1.28) when adjusted for sex, age, baseline ASDAS with CRP, smoking status, disease duration, HLA-B27 and prescribed biologic. CONCLUSIONS: Although there appeared to be some differences in the baseline characteristics when exploring this cohort according to radiographic status, which are likely related to the natural history of the disease, the level of biologic response and drug survival was comparable between nr-axSpA and r-axSpA.

Outcomes and treatment responses, including work productivity, among people with axial spondyloarthritis living in urban and rural areas: a mixed-methods study within a national register.

OBJECTIVE: To examine differences in clinical and patient-reported outcomes, including work, in individuals with axial spondyloarthritis (axSpA) living in rural and urban settings. METHODS: Using a sequential, explanatory mixed-method design, data from the British Society for Rheumatology Biologics Register for Ankylosing Spondylitis were used to (1) characterise participants with axSpA living in rural and urban areas and (b) assess any differences in outcome after commencement of biologic therapy (phase 1). Semistructured interviews (phase 2) further explored the results from phase 1. RESULTS: Patients with axSpA living in rural areas were older and more likely to work in a physical job. Among patients prescribed biologics, there were no differences in response to biologics, but after adjustment for age, sex and local area deprivation rural dwellers reported more presenteeism and overall work impairment. Work effects could be explained by accounting for individual differences in disease activity, fatigue, physical function and job type. Interviews highlighted the complex relationship between clinical factors, contextual factors (work environment, job demands) and work disability. The ability to work and flexibility in terms of what, when and how tasks are undertaken were important. Support from employers was variable and healthcare professionals were often perceived as unsupportive. CONCLUSIONS: Patients with axSpA living in rural areas report a greater impact of their disease on work productivity. New measures are needed to capture important contextual factors and comprehensively determine the impact of long-term conditions on work. Future European League Against Rheumatism axSpA recommendations should include support to work as a target to optimise quality of life in patients with axSpA.

Quantifying and predicting the effect of anti-TNF therapy on axSpA-related fatigue: results from the BSRBR-AS registry and meta-analysis.

OBJECTIVES: Effective management of axial spondyloarthritis (axSpA)-related fatigue is a major unmet clinical need. Anti-TNF therapy may reduce fatigue levels, although any effect has yet to be definitively quantified and predictors of any such improvements are unknown. METHODS: The British Society of Rheumatology Register in Axial Spondyloarthritis (BSRBR-AS) prospectively recruited axSpA patients across the UK. Changes in fatigue levels (measured using the Chalder Fatigue Scale) >1 year were compared between those starting anti-TNF therapy at the time of recruitment and those not. Differences between treatment groups were adjusted using propensity score matching. Results were meta-analysed with the extant literature to calculate pooled estimates. Then, among those BSRBR-AS anti-TNF commencers with clinically relevant fatigue, baseline predictors of response were investigated. RESULTS: Of the 998 BSRBR-AS recruits with complete fatigue data, 310 were anti-TNF commencers. At 1-year follow-up, the former group reported a mean fatigue change of -2.6 (95% CI -4.1, -1.9) points while the latter reported a mean worsening of fatigue by 0.2 points. Following propensity score adjustment, those commencing anti-TNF therapy reduced fatigue by 3.0 points compared with those not. Of those with significant fatigue and commencing anti-TNF, poor sleep quality at baseline predicted fatigue improvement. In the meta-analysis, including 1109 subjects, treatment with anti-TNF therapy resulted in a significant improvement in fatigue [Standardized mean difference (SMD) = 0.36, 95% CI 0.15, 1.56]. CONCLUSION: Anti-TNF therapy results in a significant but modest reduction in fatigue amongst axSpA patients, with those reporting poor sleep quality most likely to report improvement. Effective management will likely require additional approaches.

Real-world evidence of TNF inhibition in axial spondyloarthritis: can we generalise the results from clinical trials?

Management guidelines assume that results from clinical trials can be generalised, although seldom is data available to test this assumption. We aimed to determine the proportion of patients commencing tumour necrosis factor inhibition (TNFi) who would have been eligible for relevant clinical trials, and whether treatment response differs between these groups and the trials themselves. The British Society for Rheumatology Biologics Register for Ankylosing Spondylitis (BSRBR-AS) recruited a real-world cohort of TNFi-naïve spondyloarthritis patients with data collection from clinical records and patient questionnaires. Participant characteristics were extracted from trials identified from a recent Health Technology Assessment of TNFi for ankylosing spondylitis/non-radiographic axial spondyloarthritis. Descriptive statistics were used to determine the differences, including treatment response, between BSRBR-AS participants who would/would not have been eligible for the clinical trials and with trial participants. Among 2420 BSRBR-AS participants, those commencing TNFi (34%) had shorter symptom duration (15 vs 22 years) but more active disease (Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) 6.4 vs 4.0; Bath Ankylosing Spondylitis Disease Functional Index (BASFI) 6.2 vs 3.8). Of those commencing TNFi, 41% met eligibility criteria for ≥1 of fourteen relevant trials; they reported higher disease activity (BASDAI 6.9 vs 6.1) and poorer function (BASFI 6.6 vs 6.0). 61.7% of trial participants reported a positive treatment response, vs 51.3% of BSRBR-AS patients (difference: 10.4%; 95% CI 4.4% to 16.5%). Potential eligibility for trials did not influence treatment response (difference 2.0%; -9.4% to 13.4%). Fewer patients in the real world respond to TNFi than is reported in the trial literature. This has important implications for the generalisability of trial results, and the cost-effectiveness of TNFi agents.

Predicting response to anti-TNFα therapy among patients with axial spondyloarthritis (axSpA): results from BSRBR-AS.

OBJECTIVES: While many axSpA patients, eligible to receive anti-TNFα therapy, derive benefit when prescribed them, some patients do not. The current study aims to identify modifiable targets to improve outcome as well as non-modifiable targets that identify groups less likely to derive benefit. METHODS: The BSRBR-AS is a prospective cohort study of axSpA patients who, at recruitment, were naïve to biologic therapy. Those in the 'biologic' sub-cohort commenced their first anti-TNFα therapy at recruitment or during follow-up. Prior to commencement, information was collected on socio-economic, clinical and patient-reported factors. Outcome was assessed according to ASAS20, ASAS40, ASDAS reduction and achieving a moderate/inactive ASDAS disease state. RESULTS: 335 participants commenced their first anti-TNFα therapy and were followed up at a median of 14 (inter-quartile range 12-17) weeks. Response varied between 33% and 52% according to criteria used. Adverse socio-economic factors, fewer years in education predicted lower likelihood of response across outcome measures as did not working full-time. Co-morbidities and poor mental health were clinical and patient-reported factors, respectively, associated with lack of response. The models, particularly those using ASDAS, were good at predicting those who did not respond (negative predictive value (NPV) 77%). CONCLUSION: Some factors predicting non-response (such as mental health) are modifiable but many (such as social/economic factors) are not modifiable in clinic. They do, however, identify patients who are unlikely to benefit from biologic therapy alone. Priority should focus on how these patients receive the benefits that many derive from such therapies.

Determining factors related to poor quality of life in patients with axial spondyloarthritis: results from the British Society for Rheumatology Biologics Register (BSRBR-AS).

OBJECTIVE: To determine modifiable factors associated with poor quality of life (QoL) in patients with axial spondyloarthritis (axSpA). METHODS: Analysis of data from the British Society for Rheumatology Biologics Register in Ankylosing Spondylitis (BSRBR-AS) and validation of a previous model using data from 1810 patients with axSpA recruited during 2012-2017. Data collected included clinical and patient-reported measures. QoL was assessed using the Ankylosing Spondylitis Quality of Life (ASQoL) measure. Linear regression models predicting ASQoL scores were used first to validate a previous model from a national study, to extend this with additional information available in BSRBR-AS and finally to identify a 'de novo' model from BSRBR-AS of which factors impact on poor QoL. RESULTS: Four out of five factors included in a previous model of poor QoL in patients with axSpA were confirmed: Bath Ankylosing Spondylitis Disease Activity Index and Bath Ankylosing Spondylitis Functional Index, fatigue and widespread pain, although the performance of the model was improved by the addition of measures of mood and sleep disturbance. In a de novo model in BSRBR-AS, there were six factors (other than disease activity and function) that predicted ASQoL: depression (ß=0.16), sleep disturbance (ß=0.08), activity impairment (ß=0.04), fibromyalgia (Symptom Severity Scale (ß=0.24) and Widespread Pain Index (ß=0.10)) and tobacco smoking (ß=0.66). CONCLUSION: This study confirms that poor QoL in patients with axSpA, in addition to high disease activity and poor function, is independently influenced by sleep disturbance, mood and widespread pain. These additional factors are not considered targets for treatment in current European League Against Rheumatism (EULAR) guidelines for managing the condition.

AxSpA patients who also meet criteria for fibromyalgia: identifying distinct patient clusters using data from a UK national register (BSRBR-AS).

BACKGROUND: Around 1 in 8 patients with axial spondyloarthritis (axSpA) also meet criteria for fibromyalgia and such patients have considerable unmet need. Identifying effective therapy is important but to what extent fibromyalgia-like symptoms relate to axSpA disease severity has not been established. The aim of the current analysis was to determine whether distinct clusters of axSpA patients exist and if so to determine a) whether they differ in terms of prevalence of fibromyalgia and b) the features of patients in clusters with high prevalence. METHODS: The British Society for Rheumatology Biologics Register (BSRBR-AS) recruited axSpA patients from 83 centres 2012-2017. Clinical data, and information from patients was collected (including research criteria for fibromyalgia). Cluster analysis was undertaken using split samples for development and validation both in the whole population and the sub-group which met fibromyalgia criteria. RESULTS: One thousand three hundred thirty-eight participants were included of whom 23% met research criteria for fibromyalgia. Four clusters were identified. Two exhibited very high disease activity, one which was primarily axial (n = 347) and a smaller cluster (n = 32) with axial and peripheral disease, and in both groups more than half of members met criteria for fibromyalgia. The remaining two clusters (n = 437, n = 462) had overall less severe disease however the one which showed greater disease activity and poorer quality of life had a higher proportion meeting fibromyalgia criteria (16% v. 4%). Within those meeting fibromyalgia criteria there were three clusters. The two main groups were defined by level of symptom severity with a smaller third cluster noted to have high average swollen and tender joint counts and high levels of comorbidity. CONCLUSIONS: The major feature defining clusters with a high proportion of persons meeting criteria for fibromyalgia is high axSpA disease activity although clusters with features of fibromyalgia in the absence of high disease activity also show moderately high prevalence. Management may be most successful with pharmacologic therapy to target inflammation but enhanced by the concurrent use of non-pharmacologic therapy in such patients.

Identifying Persons with Axial Spondyloarthritis At Risk of Poor Work Outcome: Results from the British Society for Rheumatology Biologics Register.

OBJECTIVE: First, to test the hypothesis that, among working patients with axial spondyloarthritis (axSpA), those who report issues with reduced productivity at work (presenteeism) are at higher risk of work absence (absenteeism), and patients who report absenteeism are at higher risk of subsequently leaving the workforce. Second, to identify characteristics of workers at high risk of poor work outcome. METHODS: The British Society for Rheumatology Biologics Register in Ankylosing Spondylitis has recruited patients meeting Assessment of Spondyloarthritis international Society criteria for axSpA from 83 centers. Data collection involved clinical and patient-reported measures at recruitment and annually thereafter, including the Work Productivity and Activity Impairment scale. Generalized estimating equations were used to identify factors associated with poor work outcomes. RESULTS: Of the 1188 participants in this analysis who were working at recruitment, 79% reported some presenteeism and 19% some absenteeism in the past week owing to their axSpA. Leaving employment was most strongly associated with previous absenteeism (RR 1.02 per % increase in absenteeism, 95% CI 1.01-1.03), which itself was most strongly associated with previous presenteeism, a labor-intensive job, and peripheral joint involvement. High disease activity, fatigue, a labor-intensive job, and poorer physical function were all independently associated with future presenteeism. CONCLUSION: Clinical and patient-reported factors along with aspects of work are associated with an increased risk of axSpA patients having a poor outcome in relation to work. This study has identified modifiable factors as targets, facilitating patients with axSpA to remain productive at work.

AAPT Diagnostic Criteria for Fibromyalgia.

Fibromyalgia (FM) is a common chronic pain disorder that presents diagnostic challenges for clinicians. Several classification, diagnostic and screening criteria have been developed over the years, but there continues to be a need to develop criteria that reflect the current understanding of FM and are practical for use by clinicians and researchers. The Analgesic, Anesthetic, and Addiction Clinical Trial Translations Innovations Opportunities and Networks (ACTTION) public-private partnership with the U.S. Food and Drug Administration (FDA) and the American Pain Society (APS) initiated the ACTTION-APS Pain Taxonomy (AAPT) to develop a diagnostic system that would be clinically useful and consistent across chronic pain disorders. The AAPT established an international FM working group consisting of clinicians and researchers with expertise in FM to generate core diagnostic criteria for FM and apply the multidimensional diagnostic framework adopted by AAPT to FM. The process for developing the AAPT criteria and dimensions included literature reviews and synthesis, consensus discussions, and analyses of data from large population-based studies conducted in the United Kingdom. The FM working group established a revised diagnosis of FM and identified risk factors, course, prognosis, and pathophysiology of FM. Future studies will assess the criteria for feasibility, reliability, and validity. Revisions of the dimensions will also be required as research advances our understanding of FM. PERSPECTIVE: The ACTTION-APS FM taxonomy provides an evidence-based diagnostic system for FM. The taxonomy includes diagnostic criteria, common features, comorbidities, consequences, and putative mechanisms. This approach might improve the recognition of FM in clinical practice.

Associations between smoking and extra-axial manifestations and disease severity in axial spondyloarthritis: results from the BSR Biologics Register for Ankylosing Spondylitis (BSRBR-AS).

OBJECTIVE: The effects of smoking on disease manifestations in axial SpA are inadequately described. Utilizing a large and well-characterized cohort, we investigated the association between smoking and extra-axial manifestations, and smoking and disease severity measures. METHODS: Baseline data from the British Society for Rheumatology Biologics Register for Ankylosing Spondylitis were explored. Our analyses focused on extra-axial manifestations and other disease severity measures, including scales for fatigue, sleep, anxiety and depression. Logistic and linear models were used to quantify associations between disease characteristics according to smoking status (current/ex/never) and quantity (heavy/light), adjusting for age, gender, BMI, education, deprivation, comorbidities, symptom duration and alcohol status. RESULTS: A total of 2031 participants were eligible for the current analysis (68% male, mean age 49 years). Of these, 24% were current and 32% ex-smokers. When compared with non-smokers, current smokers had lower odds of uveitis [OR 0.7, 95% CI 0.5-0.9] and higher odds of psoriasis (ORadj 1.6, 95% CI 1.1-2.3). Ex- and current smokers had incrementally more severe disease than never smokers, with higher BASDAI (ß = 0.3, 95% CI 0.1-0.6; ß = 0.9, 95% CI 0.6-1.2) and BASFI (ß = 0.5, 95% CI 0.2-0.8; ß = 1.3, 95% CI 1.0-1.6); similar associations were observed for fatigue, sleep, anxiety and depression. CONCLUSION: In this large cross-sectional study, we observed that smoking is independently associated with an adverse disease profile in axial SpA, including worse fatigue, sleep, anxiety and depression, and higher odds of psoriasis. The paradoxical association between current smoking and reduced odds of uveitis is interesting and warrants further investigation.

Five Potentially Modifiable Factors Predict Poor Quality of Life in Ankylosing Spondylitis: Results from the Scotland Registry for Ankylosing Spondylitis.

OBJECTIVE: A chronic inflammatory condition manifesting in young adulthood, ankylosing spondylitis (AS) affects both physical and emotional quality of life (QOL). To inform future intervention strategies, this study aimed to (1) assess the QOL of patients with AS, and (2) identify potentially modifiable factors associated with reporting poor QOL. METHODS: The Scotland Registry for Ankylosing Spondylitis collects clinical and patient-reported data on clinically diagnosed patients with AS across Scotland. QOL is measured using the ASQoL questionnaire [range: 0 (high) to 18 (poor)]. Potentially modifiable factors associated with reporting poor QOL (score 12-18) were examined using Poisson regression models, adjusted for a variety of demographic characteristics, plus various nonmodifiable factors. Results are given as risk ratios (RR) with 95% CI. RESULTS: Data were available on 959 patients: 74% male, mean age 52 years (SD 13), median ASQoL 7.0 (interquartile range 2-12). Although many factors were univariately associated with poor QOL, 5 were identified as independent predictors: reporting moderate/severe fatigue (RR 1.60, 95% CI 1.13-2.28), poor physical function [Bath Ankylosing Spondylitis Functional Index (BASFI) ≥ 4: 3.46, 1.76-6.82], chronic widespread pain (CWP; 1.92, 1.33-2.75), high disease activity [Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) ≥ 4: 1.52, 1.09-2.12], and poor spinal mobility [Bath Ankylosing Spondylitis Metrology Index (BASMI) ≥ 4: 1.52, 0.93-2.50]. For these factors, population-attributable risks ranged between 20% (disease activity) and 56% (physical function). CONCLUSION: We have identified 5 potentially modifiable factors independently associated with poor QOL. These findings provide evidence that in addition to traditional clinical targets (BASDAI, BASFI, and BASMI), focus on nonspecific symptoms (CWP and fatigue), perhaps with nonpharmacological therapies, may yield important improvements in QOL.

Impact of Moving From a Widespread to Multisite Pain Definition on Other Fibromyalgia Symptoms.

OBJECTIVE: To investigate whether associations between pain and the additional symptoms associated with fibromyalgia are different in persons with chronic widespread pain (CWP) compared to multisite pain (MSP), with or without joint areas. METHODS: Six studies were used: 1958 British birth cohort, Epidemiology of Functional Disorders, Kid Low Back Pain, Managing Unexplained Symptoms (Chronic Widespread Pain) in Primary Care: Involving Traditional and Accessible New Approaches, Study of Health and its Management, and Women's Health Study (WHEST; females). MSP was defined as the presence of pain in ≥8 body sites in adults (≥10 sites in children) indicated on 4-view body manikins, conducted first to include joints (positive joints) and second without (negative joints). The relationship between pain and fatigue, sleep disturbance, somatic symptoms, and mood impairment was assessed using logistic regression. Results are presented as odds ratios (ORs) with 95% confidence intervals (95% CIs). RESULTS: There were 34,818 participants across the study populations (adults age range 42-56 years, male 43-51% [excluding WHEST], and CWP prevalence 12-17%). Among those reporting MSP, the proportion reporting CWP ranged between 62% and 76%. Among those reporting the symptoms associated with fibromyalgia, there was an increased likelihood of reporting pain, the magnitude of which was similar regardless of the definition used. For example, within WHEST, reporting moderate/severe fatigue (Chalder fatigue scale 4-11) was associated with a >5-fold increase in likelihood of reporting pain (CWP OR 5.2 [95% CI 3.9-6.9], MSP-positive joints OR 6.5 [95% CI 5.0-8.6], and MSP-negative joints OR 6.5 [95% CI 4.7-9.0]). CONCLUSION: This large-scale study demonstrates that regardless of the pain definition used, the magnitude of association between pain and other associated symptoms of fibromyalgia is similar. This finding supports the continued collection of both when classifying fibromyalgia, but highlights the fact that pain may not require to follow the definition outlined within the 1990 American College of Rheumatology criteria.

Disease Severity in Never Smokers, Ex-Smokers, and Current Smokers With Axial Spondyloarthritis: Results From the Scotland Registry for Ankylosing Spondylitis.

OBJECTIVE: To examine the relationship between smoking, smoking cessation, and disease characteristics and quality of life (QoL) in spondyloarthritis. METHODS: The Scotland Registry for Ankylosing Spondylitis collects data from clinically diagnosed patients with spondyloarthritis. Clinical data, including Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and the Bath Ankylosing Spondylitis Functional Index (BASFI) scores, were obtained from medical records. Mailed questionnaires contained information on smoking status and QoL (Ankylosing Spondylitis QoL questionnaire [ASQoL]). Linear and logistic regression were used to quantify the effect of smoking, and smoking cessation, on various disease-specific and QoL outcomes, with adjustments for age, sex, deprivation, education level, and alcohol use. Results are presented as regression coefficients (ß) or odds ratios (ORs) with 95% confidence intervals (95% CIs). RESULTS: Data were obtained from 946 participants (73.5% male, mean age 52 years). Current smoking was reported by 22%, and 38% were ex-smokers. Ever smokers had poorer BASDAI (ß = 0.5 [95% CI 0.2, 0.9]) and BASFI scores (ß = 0.8 [95% CI 0.4, 1.2]), and reported worse QoL (ASQoL ß = 1.5 [95% CI 0.7, 2.3]). Compared to current smokers, ex-smokers reported less disease activity (BASDAI ß = -0.5 [95% CI -1.0, -0.04]) and significantly better QoL (ASQoL ß = -1.2 [95% CI -2.3, -0.2]). They also were more likely to have a history of uveitis (OR 2.4 [95% CI 1.5, 3.8]). CONCLUSION: Smokers with spondyloarthritis experience worse disease than those who are never smokers. However, this study provides new evidence that, among smokers, smoking cessation is associated with lower disease activity and better physical function and QoL. Clinicians should specifically promote smoking cessation as an adjunct to usual therapy in patients with spondyloarthritis.

Differences in the prevalence of ankylosing spondylitis in primary and secondary care: only one-third of patients are managed in rheumatology.

OBJECTIVE: Knowing not only the prevalence of SpA, but also the proportion managed in rheumatology, has implications for health care planning. The aims of this study were to determine the prevalence of SpA and the proportion managed in rheumatology and to examine differences in group characteristics. METHODS: For the primary care population, we used the Primary Care Clinical Informatics Unit Research (PCCIUR) electronic primary care database, covering one-third of the Scottish population. Patients with AS, and various extraspinal manifestations were identified using Read Codes. For secondary care, we used the Scotland Registry for Ankylosing Spondylitis, which collected data on clinically diagnosed AS patients >15 years of age seen in rheumatology clinics between 2010 and 2013. Prevalence estimate denominators were computed using the adult PCCIUR and Scottish 2011 mid-year population estimates, respectively. Differences in the characteristics of both patient groups were examined using simple descriptive statistics. RESULTS: The prevalence of AS in primary care was 13.4/10 000 (95% CI 12.8, 14.0) and 4.7/10 000 in rheumatology (95% CI 4.5, 4.9). Rheumatology patients were younger overall and at diagnosis (mean age 51 vs 62 years and 35 vs 38, respectively; both P < 0.001) and more likely to have a history of uveitis (34 vs 22%), IBD (12 vs 6%) and psoriasis (14 vs 6%) (all P < 0.001). CONCLUSIONS: This is the first study to estimate the prevalence of clinically diagnosed AS in primary and secondary care simultaneously, indicating that only one-third of patients are managed in rheumatology. This has important ramifications for health care planning and indicates a large 'silent' proportion of patients who may have serious pathology and would benefit from additional assessment in a specialist clinic.

Management of Widespread Pain and Fibromyalgia.

Specialists' views of fibromyalgia (FM) are typically colored by their experiences of the selected, complex cases that they are regularly called to evaluate. At a population level, it is crucial to recognize that education which promotes patient empowerment and non-pharmacological interventions which support self-management are very effective. The temptation, for both physician and patient, to first reach for pharmacological interventions should be resisted until such holistic approaches are explored. In particular, a strong evidence base supports graded exercise and cognitive behavioral therapies, but such treatments must be intelligently "prescribed." As reflected by the recent ACR criteria, FM is a highly heterogeneous disorder and is not simply a disorder of pain. For some patients, co-occurring symptoms, such as fatigue, can be equally as impactful and so management strategies should be sufficiently versatile to target those dimensions which are considered priorities at the level of the individual patient. In those patients who do require pharmacological support, patients should not be led to expect significant gains in isolation. The importance of self-management requires emphasis at each and every tier of management. It is true that advances in our understanding of neurobiology have greatly informed the selection of adjunctive drug classes which may provide benefit (as well as those which do not-as is the case of opioids). However, further unpicking of pathogenesis is still required if the FM landscape is to move further towards drug-led management.