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Background The recombinant protein-based vaccine, NVX-CoV2373, demonstrated 89.7% efficacy against coronavirus disease 2019 (COVID-19) in a phase 3, randomized, observer-blinded, placebo-controlled trial in the United Kingdom. The protocol was amended to include a blinded crossover. Data to the end of the placebo-controlled phase are reported. Methods Adults aged 18–84 years received 2 doses of NVX-CoV2373 or placebo (1:1) and were monitored for virologically confirmed mild, moderate, or severe COVID-19 (onset from 7 days after second vaccination). Participants who developed immunoglobulin G (IgG) against nucleocapsid protein but did not show symptomatic COVID-19 were considered asymptomatic. Secondary outcomes included anti-spike (S) IgG responses, wild-type virus neutralization, and T-cell responses. Results Of 15 185 participants, 13 989 remained in the per-protocol efficacy population (6989 NVX-CoV2373, 7000 placebo). At a maximum of 7.5 months (median, 4.5) postvaccination, there were 24 cases of COVID-19 among NVX-CoV2373 recipients and 134 cases among placebo recipients, a vaccine efficacy of 82.7% (95% confidence interval [CI], 73.3%–88.8%). Vaccine efficacy was 100% (95% CI, 17.9%–100.0%) against severe disease and 76.3% (95% CI, 57.4%–86.8%) against asymptomatic disease. High anti-S and neutralization responses to vaccination were evident, together with S-protein–specific induction of interferon-γ secretion in peripheral blood T cells. Incidence of serious adverse events and adverse events of special interest were similar between groups. Conclusions A 2-dose regimen of NVX-CoV2373 conferred a high level of ongoing protection against asymptomatic, symptomatic, and severe COVID-19 through >6 months postvaccination. A gradual decrease of protection suggests that a booster may be indicated. Clinical Trials Registration EudraCT, 2020-004123-16.

Abstract Objective To assess the longer term impact of the COVID-19 pandemic on the self-reported physical and mental health of people with inflammatory rheumatic diseases (IRDs). Methods Two thousand twenty-four patients with IRDs were randomly selected from electronic health records. Survey invitations were sent (August 2021 coinciding with relaxation of UK COVID-19 restrictions) using SMS and postal approaches. Self-reported data included demographics, shielding status and physical (MSK-HQ) and mental health (PHQ8 and GAD7). Results Six hundred thirty-nine people completed the survey (mean (SD) age 64.5 (13.1) years, 384 (60%) female). Moderate/severe impact of the pandemic on physical and mental health was reported by 250 (41%) and 241 (39%) respectively. One hundred seventy-two (29%) reported moderate/severe depression (PHQ8 ≥ 10) and 135 (22%) moderate/severe anxiety (GAD7 ≥ 10). Females reported greater impacts of the pandemic on physical health (44% vs 34%), mental health (44% vs 34%), arthritis symptoms (49% vs 36%) and lifestyle factors (weight gain and reduced exercise and physical activity) than males. The physical and mental impacts were less in people with RA compared with other IRDs. Physical health impacts did not differ between age groups, but younger patients reported greater impacts on mental health. Conclusion The COVID-19 pandemic has had a significant impact on the physical and mental health of people with IRDs. These effects were greatest in females. Recovery needs to address the negative impact of the pandemic on lifestyle factors to minimise the long-term impacts for people with IRDs. Key Points• The pandemic had a significant impact on long term physical and mental health in almost 40% of people with IRDs.• The impact of the pandemic was greater in women for physical health, mental health and arthritis symptoms.• Many people reported negative pandemic impacts on lifestyle factors including weight and physical activity.

Background The safety and immunogenicity profile of COVID-19 vaccines when administered concomitantly with seasonal influenza vaccines have not yet been reported. We therefore aimed to report the results of a substudy within a phase 3 UK trial, by evaluating the safety, immunogenicity, and efficacy of NVX-CoV2373 when co-administered with licensed seasonal influenza vaccines. Methods We did a planned exploratory substudy as part of the randomised, observer-blinded, placebo-controlled, phase 3 trial of the safety and efficacy of the COVID-19 vaccine (NVX-CoV2373) by co-administrating the influenza vaccine at four study hospitals in the UK. Approximately, the first 400 participants meeting the main study entry criteria—with no contraindications to influenza vaccination—were invited to join the substudy. Participants of the main study were randomly assigned (1:1) to receive two intramuscular injections of either NVX-CoV2373 (5 μg) or placebo (normal saline) 21 days apart; participants enrolled into the substudy were co-vaccinated with a single (0·5 mL) intramuscular, age-appropriate (quadrivalent influenza cell-based vaccine [Flucelvax Quadrivalent; Seqirus UK, Maidenhead] for those aged 18–64 years and adjuvanted trivalent influenza vaccine [Fluad; Seqirus UK, Maidenhead] for those ≥65 years), licensed, influenza vaccine on the opposite deltoid to that of the first study vaccine dose or placebo. The influenza vaccine was administered in an open-label manner and at the same time as the first study injection. Reactogenicity was evaluated via an electronic diary for 7 days after vaccination in addition to monitoring for unsolicited adverse events, medically attended adverse events, and serious adverse events. Immunogenicity was assessed with influenza haemagglutination inhibition and SARS-CoV-2 anti-spike protein IgG assays. Vaccine efficacy against PCR-confirmed, symptomatic COVID-19 was assessed in participants who were seronegative at baseline, received both doses of study vaccine or placebo, had no major protocol deviations affecting the primary endpoint, and had no confirmed cases of symptomatic COVID-19 from the first dose until 6 days after the second dose (per-protocol efficacy population). Immunogenicity was assessed in participants who received scheduled two doses of study vaccine, had a baseline sample and at least one post-vaccination sample, and had no major protocol violations before unmasking (per-protocol immunogenicity population). Reactogenicity was analysed in all participants who received at least one dose of NVX-CoV2373 or placebo and had data collected for reactogenicity events. Safety was analysed in all participants who received at least one dose of NVX-CoV2373 or placebo. Comparisons were made between participants of the substudy and the main study (who were not co-vaccinated for influenza). This study is registered with ClinicalTrials.gov, number NCT04583995. Findings Between Sept 28, 2020, and Nov 28, 2020, a total of 15 187 participants were randomised into the main phase 3 trial, of whom 15 139 received treatment (7569 received dose one of NVX-CoV2373 and 7570 received dose one of placebo). 431 participants were co-vaccinated with a seasonal influenza vaccine in the substudy (217 received NVX-CoV2373 plus the influenza vaccine and 214 received placebo plus the influenza vaccine). In general, the substudy participants were younger, more racially diverse, and had fewer comorbid conditions than those in the main study. Reactogenicity events were more common in the co-administration group than in the NVX-CoV2373 alone group: tenderness (113 [64·9%] of 174 vs 592 [53·3%] of 1111) or pain (69 [39·7%] vs 325 [29·3%]) at injection site, fatigue (48 [27·7%] vs 215 [19·4%]), and muscle pain (49 [28·3%] vs 237 [21·4%]). Incidences of unsolicited adverse events, treatment-related medically attended adverse events, and serious adverse events were low and balanced between the co-administration group and the NVX-CoV2373 alone group. No episodes of anaphylaxis or deaths were reported within the substudy. Co-administration resulted in no change to influenza vaccine immune response although a reduction in antibody responses to the NVX-CoV2373 vaccine was noted. NVX-CoV2373 vaccine efficacy in the substudy (ie, participants aged 18 to

BackgroundThe recombinant protein-based vaccine, NVX-CoV2373, demonstrated 89.7% efficacy against coronavirus disease 2019 (COVID-19) in a phase 3, randomized, observer-blinded, placebo-controlled trial in the United Kingdom. The protocol was amended to include a blinded crossover. Data to the end of the placebo-controlled phase are reported.MethodsAdults aged 18–84 years received 2 doses of NVX-CoV2373 or placebo (1:1) and were monitored for virologically confirmed mild, moderate, or severe COVID-19 (onset from 7 days after second vaccination). Participants who developed immunoglobulin G (IgG) against nucleocapsid protein but did not show symptomatic COVID-19 were considered asymptomatic. Secondary outcomes included anti-spike (S) IgG responses, wild-type virus neutralization, and T-cell responses.ResultsOf 15 185 participants, 13 989 remained in the per-protocol efficacy population (6989 NVX-CoV2373, 7000 placebo). At a maximum of 7.5 months (median, 4.5) postvaccination, there were 24 cases of COVID-19 among NVX-CoV2373 recipients and 134 cases among placebo recipients, a vaccine efficacy of 82.7% (95% confidence interval [CI], 73.3%–88.8%). Vaccine efficacy was 100% (95% CI, 17.9%–100.0%) against severe disease and 76.3% (95% CI, 57.4%–86.8%) against asymptomatic disease. High anti-S and neutralization responses to vaccination were evident, together with S-protein–specific induction of interferon-γ secretion in peripheral blood T cells. Incidence of serious adverse events and adverse events of special interest were similar between groups.ConclusionsA 2-dose regimen of NVX-CoV2373 conferred a high level of ongoing protection against asymptomatic, symptomatic, and severe COVID-19 through >6 months postvaccination. A gradual decrease of protection suggests that a booster may be indicated.

Sonorama is a 2015 sonic artwork by Claudia Molitor, consisting of a number of audio files designed for listening on a train journey between London St Pancras and Margate, and a graphic score based on the composer's own ‘reading’ of this journey. This article analyses the relationship between the sonic and the spatial in the work, exploring how Molitor's site-specific composition interacts with its environment on multiple scales. By drawing on the strategy of ‘situated listening’ developed by Gascia Ouzounian, as well as urbanist language introduced by Richard Sennett, this article seeks to elucidate the relationship between a number of ‘nested’ spaces, present across varying realisations, and the political agenda that energises the work. Written in the midst of summer 2015's European refugee crisis, the work brings into sharp focus themes of British exceptionalism, immigration and inclusion.

Objectives COVID-19 led to rapid uptake of digital health care. We sought to examine digital access, health and digital literacy, and impact on confidence and satisfaction with remote consultations in people with inflammatory rheumatic diseases (IRDs). Methods People with IRDs (n = 2024) were identified from their electronic health record and invited to participate in a cross-sectional survey, using short message service (SMS) and postal approaches. Data were collected on demographics, self-reported diagnosis, access to and use of internet-enabled devices, health and digital literacy, together with confidence and satisfaction with remote consultations. Ethical approval was obtained (Ref 21/PR/0867). Results Six hundred and thirty-nine (639) people completed the survey [mean (s.d.) age 64.5 (13.1) years, 384 (60.1%) female]. Two hundred and eighty-seven (44.9%) completed it online. One hundred and twenty-six (19.7%) people reported not having access to an internet-enabled device. Ninety-three (14.6%) reported never accessing the internet; this proportion was highest (23%) in people with RA. One hundred and seventeen (18%) reported limited health literacy. Even in those reporting internet use, digital literacy was only moderate. People with limited health or digital literacy or without internet access were less likely to report confidence or satisfaction with remote consultations. Conclusion Limited health and digital literacy, lack of digital access and low reported internet use were common, especially in older people with RA. People with limited health literacy or limited digital access reported lower confidence and satisfaction with remote consultations. Digital implementation roll-out needs to take account of people requiring extra support to enable them to access care digitally or risks exacerbating health inequalities.

Psoriatic arthritis (PsA) is a chronic and often progressive inflammatory disease, occurring in up to 30% of patients with psoriasis. Assessment of patients with PsA requires consideration of all disease domains, including peripheral arthritis, axial disease, enthesitis, dactylitis, skin psoriasis, psoriatic nail disease, uveitis and inflammatory bowel disease. Co-morbidities and related conditions should all be considered including: obesity, metabolic syndrome, cardiovascular disease, anxiety/depression, liver disease, chronic infections, malignancy, osteoporosis, fibromyalgia and reproductive health.

Objectives: Psoriatic arthritis (PsA) has a strong genetic component, and the identification of genetic risk factors could help identify the ~30% of psoriasis patients at high risk of developing PsA. Our objectives were to identify genetic risk factors and pathways that differentiate PsA from cutaneous-only psoriasis (PsC) and to evaluate the performance of PsA risk prediction models. Methods: Genome-wide meta-analyses were conducted separately for 5,065 patients with PsA and 21,286 healthy controls and separately for 4,340 patients with PsA and 6,431 patients with PsC. The heritability of PsA was calculated as a single-nucleotide polymorphism (SNP)–based heritability estimate (h2SNP) and biologic pathways that differentiate PsA from PsC were identified using Priority Index software. The generalizability of previously published PsA risk prediction pipelines was explored, and a risk prediction model was developed with external validation. Results: We identified a novel genome-wide significant susceptibility locus for the development of PsA on chromosome 22q11 (rs5754467; P = 1.61 × 10−9), and key pathways that differentiate PsA from PsC, including NF-κB signaling (adjusted P = 1.4 × 10−45) and Wnt signaling (adjusted P = 9.5 × 10−58). The heritability of PsA in this cohort was found to be moderate (h2SNP = 0.63), which was similar to the heritability of PsC (h2SNP = 0.61). We observed modest performance of published classification pipelines (maximum area under the curve 0.61), with similar performance of a risk model derived using the current data. Conclusion: Key biologic pathways associated with the development of PsA were identified, but the investigation of risk classification revealed modest utility in the available data sets, possibly because many of the PsC patients included in the present study were receiving treatments that are also effective in PsA. Future predictive models of PsA should be tested in PsC patients recruited from primary care.

Background/Aims The COVID-19 pandemic led to an overnight shift in healthcare delivery and rapid uptake of digital technology. Such approaches risk digital exclusion for people without access to or not confident in their use of technology. We sought to examine digital access and e-health literacy in people with inflammatory conditions. Methods People (n = 2,024) were identified from their electronic health record and invited to participate in a survey, using SMS and postal approaches. Data were collected on age, gender, self-reported arthritis diagnosis (RA, PsA, AS, SLE and other), access to an internet-enabled device and frequency of internet access, health literacy (single-item literacy screener) and self-perceived e-health literacy (eHEALs). Ethical approval was obtained (Ref 21/PR/0867). Results 639 people completed the survey, of whom 287 (44.9%) completed it online. Mean (sd) age was 64.5 (13.1) years and 384 (64.7%) were female. 98.3% were white. Approximately 20% of people did not have access to an internet enabled device (Table). 93 (15.3%) of patients reported never accessing the internet, this proportion was higher in people with RA. Approximately 19% had low health literacy. In those reporting internet use, eHealth literacy was moderate. The most popular options for accessing arthritis advice were telephone helplines or appointments. Conclusion Low health literacy, lack of digital access and low reported internet use was common, especially in people with RA, leading to high use of telephone advice and rheumatology appointments. Digital roll-out needs to take account of people requiring extra support to enable them to access care or risks excluding many patients with inflammatory conditions. Disclosure S. Hider: None. S. Muller: None. L. Gray: None. F. Manning: None. M. Brooks: None. D. Heining: None. A. Menon: None. J. Packham: None. S. Raghuvanshi: None. E. Roddy: None. S. Ryan: None. I. Scott: None. Z. Paskins: None.

ObjectiveEvaluation of a psoriatic arthritis (PsA), multidimensional, patient-completed disease flare questionnaire (FLARE).MethodsThe 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).ResultsThe 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).ConclusionA 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.

BackgroundCovid-19 vaccines are urgently needed, especially against emerging variants. NVX-CoV2373 is a recombinant severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 rS) nanoparticle vaccine containing trimeric full-length SARS-CoV-2 spike glycoprotein and Matrix-M adjuvant.MethodsA phase 3, randomized, observer-blinded, placebo-controlled trial was conducted in adults 18-84 years old who received two intramuscular 5-µg doses, 21 days apart, of NVX-CoV2373 or placebo (1:1) across 33 sites in the United Kingdom. The primary efficacy endpoint was virologically confirmed symptomatic Covid-19 with onset 7 days after second vaccination in serologically negative participants.ResultsA total of 15,187 participants were randomized, of whom 7569 received NVX-CoV2373 and 7570 received placebo; 27.2% were 65 years or older, 44.7% had comorbidities and 4.2% had baseline serological evidence of SARS-CoV-2. There were 10 cases of Covid-19 among NVX-CoV2373 recipients and 96 cases among placebo recipients, with symptom onset at least 7 days after second vaccination; NVX-CoV2373 was 89.7% (95% confidence interval, 80.2 to 94.6) effective in preventing Covid-19, with no hospitalizations or deaths reported. There were five cases of severe Covid-19, all in the placebo group. Post hoc analysis revealed efficacies of 96.4% (73.8 to 99.5) and 86.3% (71.3 to 93.5) against the prototype strain and B.1.1.7 variant, respectively. Vaccine efficacy was similar across subgroups, including participants with comorbidities and those ≥65 years old. Reactogenicity was generally mild and transient. The incidence of serious adverse events was low and similar in the two groups.ConclusionA two-dose regimen of NVX-CoV2373 conferred 89.7% protection against a blend of prototype and variant Covid-19, demonstrated high efficacy against the B.1.1.7 variant, and had a reassuring safety profile.(Funded by Novavax, Inc. EudraCT number, 2020-004123-16).

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.

Background Fatigue in axSpA is described as a complex, multidimensional symptom that involve disease-specific, cognitive/behavioural and personal factors. However, current assessment guidance in axSpA recommends using a single-item visual analogue scale on fatigue severity. This type of provides a limited assessment and may fail to adequately capture the multiplicity of fatigue experience. Despite the high prevalence and significant impact of fatigue, there is currently no axSpA-specific patient-derived multi-item questionnaire for fatigue. In our previous qualitative research, we identified energy as a related but distinct component of fatigue experience in axSpA. In response, and in collaboration with our patient and public involvement (PPI) group, we have co-produced a 30-item patient-reported outcome measure (PROM) specific to axSpA-fatigue and energy: the Warwick Axial Spondyloarthritis faTigue and Energy measure (WASTEd). The aim of this study was to evaluate the quality of the WASTEd and make statistically informed item refinement decisions following completion by a UK-wide patient cohort. Methods A UK-based postal survey of 580 axSpA patients provided necessary data supporting both classic (Classic Test Theory; CTT) and modern (Rasch Measurement Theory; RMT) psychometric evaluation. CTT analysis included evaluating structural validity using exploratory factor analysis (EFA), internal consistency using Cronbach’s alpha and assessing item-total correlations. RMT analysis included evaluating evidence of local dependency between items, item fit and category characteristic curves. Results The survey response rate was 64.13% (n = 372). EFA identified four factors: energy, fatigue, symptoms and control. Five items were removed due to narrow cross-loadings. Final item-total correlations ranged from 0.61 to 0.83. Cronbach’s alpha was estimated to be 0.97. Rasch analysis highlighted one item as under discriminating. Numerous items showed evidence of respondents opting for a middle-option answer following visual inspection of the category characteristic curves. Findings were discussed with the study PRP group and co-refinement (item removal, modification or introduction) decisions were made during the meeting. A further seven items were removed to produce a final 18-item short-form version of the WASTEd. Conclusion The WASTEd has good evidence of data quality, structural validity and content validity. Psychometric evidence supports qualitative findings that energy is a distinct but related component in fatigue experience. Following a final stage of testing, the WASTEd will be ready for incorporation into both research and clinical practice settings, providing an essential patient-derived assessment of fatigue and energy with which to inform shared decision-making. Disclosures N.A. Pearson None. H. Parsons None. E. Tutton None. J. Martindale Honoraria; JM has received speaker fees and/or honoraia from Abbvie Ltd, Novartis, Pfizer and UCB. Grants/research support; JM has received a research grant from Pfizer. G. Strickland None. J. Thompson None. J. Packham None. K.L. Haywood None.

Background The last decade has witnessed significant growth in the active involvement of patients as research partners (PRPs) in health and social care research to facilitate a stronger patient-focus in research endeavours and outputs. Whilst general guidance is available - e.g. INVOLVE - there is limited guidance pertaining to how one should collaborate with patients as partners in the development of patient-reported outcome measures (PROMs). Here, we describe our active collaboration with patients as research partners in the co-production of a new PROM: the Warwick Axial Spondyloarthritis measure of faTigue and Energy (WASTEd). Methods An established PRP group contributed to the development of the initial funding application, whom received training and support from the PRP group facilitator (JM). The key stages for PRP collaboration throughout the PROM development process were jointly agreed and included: developing qualitative research topic guides and supporting data analysis; supporting development and refinement of the measurement framework to underpin the new PROM, and; supporting question (item) generation and refinement following both qualitative and quantitative explorations. All key decisions were made following face-to-face meetings between the lead research and the PRP group. Results Six face-to-face meetings were held over 2.5 years (average meeting duration 2 hours; range 1.5 to 3 hours) with between three and eight PRP members attended each meeting. Additional e-mail correspondence and summary reports were shared between meetings. The group contributed across all project stages including: developing ethics applications which included assessing the acceptability of the study to patients; generating interview topic guides and verbal probes for key issues identified by the PRP group; interpreting qualitative data with the lead researcher; co-designing and editing the draft PROM and refining the long form version of the PROM using both qualitative and statistical data. PRP collaboration was particularly integral to the appropriate use of relevant language and, most substantively, in providing a clearer understanding of the distinction between fatigue and energy. Conclusion The active collaboration with PRPs has supported the co-production of a relevant and acceptable PROM, driven by the needs and perspectives of patients. Additionally, the PRP groups were able to ensure all refinement decisions made to the PROM did not undermine the content validity of the measure. Finally, their involvement has sought to act as a check, support and challenge on inferences drawn by the researchers, enriching the process and study outcomes. Disclosures N.A. Pearson None. G. Strickland None. J. Thompson None. J. Martindale Honoraria; JM has received speaker fees and/or honoraria from Abbvie Ltd, Novartis, Pfizer and UCB. Grants/research support; JM has received a research grant from Pfizer. E. Tutton None. H. Parsons None. J. Packham None. K. Haywood None.

Background Enthesitis and dactylitis are considered characteristic inflammatory musculoskeletal manifestations of spondyloarthritis (SpA). These manifestations are usually assessed in the context of their assumed underlying specific condition rather than as distinct entities. Data from the ASAS-COMOSPA cohort have recently been shown that duration of SpA disease is associated with higher odds of hypertension particularly in axial SpA (1). Objectives To evaluate the possible associations of dactylitis and enthesitis phenotypes with cardiovascular comorbidities in a heterogeneous cohort of patients with SpA. Methods ASAS-COMOSPA is a global cross-sectional study assessing comorbidities in 3984 patients with SpA. History of enthesitis or dactylitis was based on self-report with confirmation using the medical records. Associations between dactylitis or enthesitis with hypertension, dyslipidaemia, diabetes, ischemic heart diseases (IHD) and stroke were analysed by separate logistic regression models unadjusted, adjusted for age and sex (models 1), and adjusted for age, sex and BMI (model 2). Results The data of 3905 participants were available for analysis. There were 1480 (37.9%) with history of enthesitis and 611 (15.6%) with dactylitis, while 1814 (46.5%) had neither. Presence of dactylitis was associated with hypertension in the univariable analysis [OR=1.68; 95%CI: 1.39– 2.03]. The association remained significant when adjusted for age and sex, but not following further adjustment for BMI (Table). Similarly, enthesitis was associated with hypertension in the univariable analysis [OR=1.36; 95%CI: 1.17-1.59], which remained after adjusted for age and sex, as well as after further adjustment for BMI (Table). Similar associations were seen for dyslipidaemia and dactylitis [OR=1.60; 95%CI: 1.29– 1.98] or enthesitis [OR=1.50; 95%CI: 1.26-1.77], with the association with dactylitis lost after further adjustment for BMI while the association with enthesitis remained significant (Table). While there were significant associations between dactylitis and diabetes [OR: 1.50 (95% CI: 1.07–2.11)], and between enthesitis and diabetes [OR=1.35; 95%CI: 1.02-1.78] in unadjusted models, no associations were seen after adjustments. There were no significant associations between dactylitis or enthesitis and either IHD or stroke (Table). Conclusion In patients with SpA, both dactylitis and enthesitis are associated with higher risk of hypertension and dyslipidaemia. The loss of associations with dactylitis with adjustment for BMI could suggest a potential shared underlying metabolic mechanism. Reference [1] Derakhshan MH, et al. J Rheumatol 2019;180538 Disclosure of Interests Mohammad H. Derakhshan: None declared, Nicola Goodson Grant/research support from: Research support grant from Novartis, Speakers bureau: Paid speaker UCB, Jonathan Packham Consultant for: Educational speaker grant from Abbvie, Raj Sengupta Grant/research support from: Celgene, Novartis, Consultant for: Abbvie, Biogen, Celgene, Novartis, UCB, Speakers bureau: Abbvie, Biogen, Celgene, Novartis, UCB, Anna Molto: None declared, Helena Marzo-Ortega Grant/research support from: Janssen, Novartis and Pfizer, Consultant for: AbbVie, Celgene, Janssen, Eli-Lilly, Novartis and UCB, Speakers bureau: AbbVie, Celgene, Janssen, Eli-Lilly, Novartis and UCB, Stefan Siebert Grant/research support from: AbbVie, Novartis, Pfizer, Janssen, BMS, Celgene, UCB, and Boehringer Ingelheim, Consultant for: AbbVie, UCB, Pfizer, Janssen, Boehringer Ingelheim, Celgene, and Novartis, Speakers bureau: AbbVie, UCB, Pfizer, Janssen, Boehringer Ingelheim, Celgene, and Novartis

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.

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.\ud \ud 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.\ud \ud 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.\ud \ud SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42016042271 ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13643-018-0777-7) contains supplementary material, which is available to authorized users.

Background Inflammatory bowel disease (IBD) is an established extra-articular manifestation of Spondyloarthritis (SpA). The association of SpA with other gastrointestinal and hepatic comorbidities is less well known. Objectives To examine the relationship between SpA disease duration and gastrointestinal comorbidities other than IBD. Methods ASAS-COMOSPA is a large global cross-sectional study comprising 3984 patients with SpA. We evaluated the association between “SpA disease duration” (defined in 5 year blocks) and upper gastrointestinal ulcers, hepatitis B (HBV), hepatitis C (HCV) and diverticulitis. Binary logistic regression models were created, adjusted for age, sex, BMI, smoking, alcohol, NSAIDs, DMARDs, biologics, steroids and IBD history. Subgroup analysis was performed, stratified by peripheral and/or axial joint involvement. Results The data of 3923 patients (64.9% male) were available for analysis, 5.3% of whom had a history of IBD. The self-reported prevalence of other gastrointestinal conditions was: upper gastrointestinal ulcers 10.7%; viral hepatitis 4.7% and diverticulitis 1.5%, with significant geographic variation. “SpA disease duration” was not associated with the occurrence of the upper gastrointestinal ulcers (OR=0.98, 95% CI: 0.92–1.05), HBV (OR=0.43, 95% CI: 0.28–0.67) or HCV (OR=0.27, 95% CI: 0.11–0.62). In contrast, the risk of diverticulitis was significantly increased by “SpA disease duration” (OR=1.14, 95% CI: 1.01–1.29); increased risk of 14% for every 5 years of disease duration) across the entire cohort, after adjustment for potential confounders, including age. Confounding variables showing significant association with diverticulitis were current age (OR=1.06, 95% CI: 1.04–1.08) and high alcohol (³3 units/day) intake (OR=3.84, 95% CI: 1.62–9.07) but not medication history (table 1). Subgroup analyses revealed stronger association of SpA disease duration with diverticulitis in those with axial (OR=1.24, 95% CI: 1.08–1.42) than those with peripheral (OR=1.12, 95% CI: 0.98–1.29) SpA disease. Conclusions Patients with SpA have a number of gastrointestinal comorbidities, including increased risk of diverticulitis with increased SpA disease duration, highest in those with axial disease. The reasons for this association are unclear and warrant further investigation. Diverticulitis should be considered, in addition to IBD, when patients with SpA present with lower gastrointestinal symptoms. Disclosure of Interest None declared

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.

Background Spondyloarthritis (SpA) is associated with adverse bone health outcomes. It is not known whether age at disease diagnosis is associated with osteoporosis and fracture in later life. Objectives To examine the relationship between “younger age at SpA diagnosis” and risk of osteoporosis and fractures (vertebral and low-trauma peripheral). Methods COMOSPA is a large global cross-sectional study comprising 3984 patients with SpA from 23 countries1. We evaluated the association between “younger age at SpA diagnosis” (categorised into 5-year blocks) and vertebral fracture, low-trauma peripheral fracture, and osteoporosis (t Results Data were available for 3923 participants (64% male). Median age at SpA diagnosis was 33 (IQR 25–43) years. Younger age at SpA diagnosis was not associated with the risk of vertebral fractures in the entire cohort (OR=1.11, p =0.143) nor in the subgroup with axial SpA involvement, but was increased in those with peripheral arthritis (OR=1.26, p =0.014) indicating 26% excess risk for each 5-year younger age at time of SpA diagnosis. There was no significant association between younger age at diagnosis and the risk of low trauma peripheral fractures or spinal osteoporosis in the entire cohort or any subgroups. Younger age at SpA diagnosis was associated with higher risk of hip osteoporosis in the entire cohort (OR=1.34, p =0.004) and both subgroups. Femoral neck osteoporosis demonstrated similar associations (Table). Conclusions Younger age of SpA diagnosis was associated with higher risk of vertebral fracture in patients with peripheral arthritis but not axial disease in this study. Lack of association with vertebral fracture and spinal osteoporosis in axial disease may reflect difficulty in detecting spinal disease and osteoporosis in the presence of spinal pain and syndesmophytes. An association between hip osteoporosis and younger age at SpA diagnosis was noted. References Ann Rheum Dis 2016;75:1016–23. Disclosure of Interest None declared

Background Spondyloarthritis (SpA) and chronic inflammatory diseases are associated with a number of cardiovascular comorbidities. It is unknown whether age at SpA diagnosis is associated with cardiovascular outcomes in later life. Objectives To examine the relationship between “younger age at SpA diagnosis” and risk of various cardiovascular comorbidities. Methods COMOSPA is a large worldwide cross-sectional study comprising 3984 patients from 23 countries evaluating comorbidities in patients with SpA (1). We evaluated the association between “younger age at SpA diagnosis” (defined in 5-year blocks) and cardiovascular comorbidities using uni-variable and multi-variable binary logistic regression. Each model comprised one cardiovascular co-morbidity as dependent and “age at SpA diagnosis” as predictor adjusted for age, sex, BMI, history of smoking, alcohol, NSAIDs, DMARDs, biologics, steroids and other relevant factors Results The data of 3923 patients (64% male) were available for analysis. Current age ranged from 18 to 100 with median (IQR) of 42 (32–53) years. The median (IQR) age at SpA diagnosis was 33 (25–43) years. Main reported cardiovascular-related comorbidities were hypertension (22.4%), ischemic heart disease (IHD) (2.6%), stroke (1.3%) and diabetes mellitus (5.5%). The risk of hypertension, after adjustment for potential confounding factors was associated with younger age at SpA diagnosis (OR=1.10, 95% CI: 1.05 -1.16), indicating 10% higher risk of hypertension for each 5 year younger age at time of SpA diagnosis (Table). Confounding variables showing significant association with hypertension were current age (OR=1.12, 95% CI: 1.10–1.13, p The other cardiovascular comorbidities were not associated with “younger age at SpA diagnosis” after adjustments for relevant confounding factors in multivariable analyses (Table) Conclusions Younger age of SpA diagnosis is associated with increased risk of developing hypertension but not other cardiovascular comorbidities in this study. The explanation for this association is not clear and does not appear to be due to increased NSAID exposure. References Molto A, et al. Ann Rheum Dis 2016;75:1016–23. Disclosure of Interest None declared

Objective. To estimate the proportion of patients with axial spondyloarthritis (SpA) in a UK national biologics registry who met criteria for fibromyalgia (FM), and to delineate the characteristics of these patients. Methods. Two cohorts of patients are prospectively recruited from across 83 centers in the UK for the British Society for Rheumatology Biologics Register in Ankylosing Spondylitis (BSRBR-AS). All patients are required to meet Assessment of SpondyloArthritis international Society (ASAS) criteria for axial SpA. Patients are either newly starting biologic therapy (biologics cohort) or are naive to treatment with biologic agents (non-biologics cohort) at the time of recruitment, and all patients are followed up prospectively. At recruitment and follow-up, clinical information and measurements are recorded while patients complete the 2011 research criteria for FM and assessments of the level of disease activity and work impact. Results. Of the patients registered in the BSRBR-AS, 1,504 (68% male) were eligible for the current analysis, of whom 311 (20.7%) met the 2011 research criteria for FM. Prevalence of FM was similar between patients who fulfilled the modified New York criteria for AS (19.7%) and those who fulfilled ASAS imaging criteria but not the modified New York criteria (25.2%); however, among those who fulfilled only the ASAS clinical criteria, the prevalence of FM was lower (9.5%). Patients who met FM criteria reported significantly worse disease activity, function, global severity scores, and quality of life, and were more likely to have moderate or severe levels of mood disorder and clinically important fatigue. Patients who met FM criteria reported experiencing work impairment around half their working time. Meeting FM criteria was not related to elevated C-reactive protein levels or most extraspinal manifestations, but was associated with a higher likelihood of having received biologic therapy. Conclusion. Developing management approaches that would address the significant unmet clinical needs of the 1 in 5 patients with axial SpA who meet criteria for FM should be a research priority.

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.

Rheumatoid arthritis (RA) is a chronic disease associated with significant morbidity. The 2009 NICE guidance advises on the management of patients with RA. In this study, we undertook a survey to assess the implementation of the guidance into practice across the Midlands. In total, 19 rheumatology units participated, of which nine have designated early inflammatory arthritis clinics (EIAC). Data for 311 patients with RA attending clinics were collected during a two week period. The median time from symptom onset to first visit was four months. Of the patients, 95.6% were seen within 12 weeks of referral. Of those seen in EIAC, 75.9% had erosions documented on X-rays versus 49.4% of non-EIAC patients. In addition, 57.9% of patients were offered combination disease-modifying antirheumatic drugs (DMARD) therapy in EIAC, versus 30.4% in non-EIAC units. Monthly disease-activity scores were calculated more in patients attending EIAC than non-EIAC units (51.1% versus 25.4%). Based on our results, there is significant regional variation in implementation of the NICE guidance. In addition, patients with RA attending EIACs are more likely to receive a treat-to-target approach.

Here we report on an audit performed to examine compliance with National Institute for Health and Clinical Excellence (NICE) guidelines for the use of anti-tumour necrosis factor alpha (anti-TNFalpha) in treating patients with ankylosing spondylitis (AS). Data from 17 rheumatology centres across the Midlands were collected prospectively from patients with AS attending outpatient clinics and retrospectively in patients receiving anti-TNFalpha but not attending outpatient clinics during the audit. In total, 80% of the 416 patients for whom data were collected were male. Of the 238 patients recruited prospectively, 41% were receiving anti-TNFalpha. Reviewing all patients on anti-TNFalpha (N=275), pre-treatment assessments 12 weeks apart were documented in 55% of patients. After anti-TNFalpha treatment had started, regular 12-weekly assessments occurred in 46% of patients. Therefore, compliance with NICE guidance was found to vary among centres. Based on our audit, clinical capacity, and clinical or patient choice might be influencing the suboptimal adherence seen in assessment timing suggested by NICE guidelines relating to the use of anti-TNFalpha in treating patients with AS.

Objectives To investigate a shared genetic aetiology for skin involvement in psoriasis and psoriatic arthritis (PsA) by genotyping single-nucleotide polymorphisms (SNPs), reported to be associated in genome-wide association studies of psoriasis, in patients with PsA. Methods SNPs with reported evidence for association with psoriasis were genotyped in a PsA case and control collection from the UK and Ireland. Genotype and allele frequencies were compared between PsA cases and controls using the Armitage test for trend. Results Seven SNPs mapping to the IL1RN, TNIP1, TNFAIP3, TSC1, IL23A, SMARCA4 and RNF114 genes were successfully genotyped. The IL23A and TNIP1 genes showed convincing evidence for association (rs2066808, p = 9.1×10 −7 ; rs17728338, p = 3.5×10 −5 , respectively) whilst SNPs mapping to the TNFAIP3, TSC1 and RNF114 genes showed nominal evidence for association (rs610604, p = 0.03; rs1076160, p = 0.03; rs495337, p = 0.0025). No evidence for association with IL1RN or SMARCA4 was found but the power to detect association was low. Conclusions SNPs mapping to previously reported psoriasis loci show evidence for association to PSA, thus supporting the hypothesis that the genetic aetiology of skin involvement is the same in both PsA and psoriasis.

Background: Sacroiliac joints (SJ) involvement is a distinctive and charasteristic feature of Spondyloarthritis (SpA) and x-ray is the test routinely used to make a diagnosis. However, x-ray reveals late structural damage but cannot detect active inflammation. The objective of this study was to assess the validity of Doppler ultrasound in SJ. Methods: Prospective blinded and controlled study of SJ, in which three populations were compared. We studied 106 consecutive cases, who were divided into three groups: a) 53 patients diagnosed with SpA who had inflammatory lumbar and gluteal pain assessed by a rheumatologist; b) 26 patients diagnosed with SpA who didn't have SJ tenderness and had normal physical examination; c) control group of 27 subjects (healthy subjetcs or with mechanical lumbar pain). All patients included that were diagnosed with SpA met almost the European Spondyloarthropathy Study Group (ESSG) classification criteria. Physical examination of the SJ included: sacral sulcus tenderness, iliac gapping, iliac compression, midline sacral thrust test, Gaenslen's test, and Patrick s test were used as gold standard. Both SJ were examined with Doppler ultrasound (General Electric Logiq 9, Wauwatosa WI, USA) fitted with a 9-14 Mhz lineal probe. The ultrasonographer was blinded to clinical data. Doppler in SJ was assessed as positive when both Doppler colour and resistance index (RI)

To examine the impact of ankylosing spondylitis (AS) on patients across the UK and to identify factors associated with unemployment, absenteeism, and presenteeism.One thousand patients with AS from 10 specialist rheumatology centres across the UK were invited to participate in a study evaluating a new outcome measure. Patients completed a questionnaire, which included questions relating to their work, sociodemographic and clinical characteristics.The questionnaire was completed by 612 patients (438 males; 72%). The mean age of the participants was 50.8 (SD 12.2) years, mean disease duration was 17.3 (SD 11.7) years, and mean symptom duration 22.4 (SD 12.4) years. A total of 206 (40%) patients of working age were not employed. Factors associated with not being employed were social deprivation [odds ratio (OR) 3.52, 95% confidence interval (CI) 2.14-5.80], poor function (OR 3.42, 95% CI 1.90-6.13), depression (OR 2.05, 95% CI 1.12-3.78), increasing age (OR 1.05 per year, 95% CI 1.02-1.08), and longer disease duration (OR 1.03 per year, 95% CI 1.01-1.06). Disease activity (OR 3.24, 95% CI 1.11-9.48) and depression (OR 3.22, 95% CI 1.22-8.48) were associated with absenteeism, while depression (OR 5.69, 95% CI 1.77-18.27, disease activity (OR 3.97, 95% CI 1.76-8.98), anxiety (OR 3.90, 95% CI 1.83-8.31), self-efficacy (OR 0.71, 95% CI 0.58-0.86), and increasing age (OR 1.04 per year, 95% CI 1.00-1.08) were associated with presenteeism.Psychological, sociodemographic, and disease-related factors were all found to be related to work status. These factors should be taken into account when considering early treatment and management. Depression, in particular, appears to be associated with employment, absenteeism, and presenteeism, and should therefore be prioritized in clinical practice.

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.

Psoriatic arthritis (PsA) is a chronic inflammatory arthritis associated with psoriasis and, despite the larger estimated heritability for PsA, the majority of genetic susceptibility loci identified to date are shared with psoriasis. Here, we present results from a case-control association study on 1,962 PsA patients and 8,923 controls using the Immunochip genotyping array. We identify eight loci passing genome-wide significance, secondary independent effects at three loci and a distinct PsA-specific variant at the IL23R locus. We report two novel loci and evidence of a novel PsA-specific association at chromosome 5q31. Imputation of classical HLA alleles, amino acids and SNPs across the MHC region highlights three independent associations to class I genes. Finally, we find an enrichment of associated variants to markers of open chromatin in CD8(+) memory primary T cells. This study identifies key insights into the genetics of PsA that could begin to explain fundamental differences between psoriasis and PsA.

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

We read with interest the recent paper by Sandberg et al 1 highlighting the negative impact of obesity on disease remission in a cohort of patients with early rheumatoid arthritis (RA). We have investigated the impact of both obesity and comorbidity on disease remission in an established RA cohort. Data were collected prospectively between 2003 and 2011 from the Haywood Hospital, North Staffordshire, UK. Patients fulfilled the 1987 American College of Rheumatology criteria for RA,2 had been followed up for 3 years and were taking conventional (non-biologic disease-modifying antirheumatic drugs (DMARDs)) at baseline. Participants underwent an annual standardised research assessment, separate to their routine clinical care, including demographics, body mass index (BMI) and disease …

Background Psoriatic arthritis (PsA) is an inflammatory arthritis that is associated with psoriasis. Although the majority of PsA genetic risk loci identified also confer risk for psoriasis, we have recently reported evidence of loci that are associated with PsA and not psoriasis, including an association at the IL23R locus which is also independent of a psoriasis variant at the same locus. Methods The PsA-specific SNP rs12044149, and the psoriasis SNP rs9988642 at the IL23R locus were genotyped in a cohort of 914 PsA cases and 6,945 controls from Spain, Crete, Germany and the UK, with the Life Technologies QuantStudio genotyping platform. Association testing was carried out using PLINK, and a meta-analysis was performed with PsA Immunochip data (1,962 cases, 8,923 controls). Genotype data was also available from the psoriasis WTCCC2 study (excluding known PsA, n=1,784) to compare effect sizes between PsA and psoriasis using multinomial logistic regression in Stata, and to directly compare PsA and psoriasis genotypes. Credible SNP sets were calculated for the PsA and psoriasis IL23R associations using the Bayesian refinement method, and functionally annotated. Results We replicated the association rs12044149 with PsA ( P =4.03x10 –6 ), which remained significant when conditioning upon the psoriasis variant, rs9988642 ( P cond =4.86x10 –6 ), and reached genome-wide significance during meta-analysis of the combined PsA dataset ( P meta =4.76x10 –20 ). Only a modest association was found for rs9988642 ( P =0.04), with no genome-wide significance found during meta-analysis ( P =4.61x10 –4 ). Within the psoriasis dataset, this association remained significant when conditioning upon rs12044149 ( P =1.0x10 –07 vs. P cond =1.63x10 –5 ). Effect estimates for rs12044149 were significantly different between PsA and psoriasis ( P =2.0x10 –3 ), and direct comparison of genotypes for PsA and psoriasis found the risk allele to be significantly increased in PsA ( P =4.52x10 –4 , OR=1.3). Credible SNPs for rs12044149 mapped to promoter and enhancer regions within memory CD8 + T cells, which we have previously reported to be critical for PsA. Conclusions We have successfully replicated a PsA-specific (associated with PsA but not psoriasis) risk variant at the IL23R locus in an independent cohort, confirming rs12044149 to be distinct from rs9988642 (r 2 =0.02). This gives five PsA-specific associations that have now been identified. Disclosure of Interest None declared

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.

IntroductionThe 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. MethodsMeasurement 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. ResultsPrincipal 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. ConclusionsA 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.

This study aims to describe the deterioration of well-established ankylosing spondylitis (AS) over a 10-year period. Patients with well-established AS under secondary care review were assessed at baseline and re-assessed after a 10-year period. Data on patient characteristics, spinal mobility and self-reported health status (AS Quality of Life, Bath AS Disease Activity Index, EuroQoL, Revised Leeds Disability Questionnaire and Short Form-12) were compared between the two time points. One hundred fifty-nine patients took part in the initial assessment. After 10 years, 69/117 patients still under secondary care follow-up attended a second assessment. At the second assessment, this cohort was predominately male (92.8 %), mean age of 48.7 years (SD 9.7) and mean disease and symptom duration of 14.9 (SD 9.0) and 21.9 years (SD 13.3), respectively. Amongst the physical and patient-reported measures, only tragus to wall (p < 0.001), cervical rotation (p = 0.001) and disability (p = 0.02) had significantly deteriorated over time. The percentage of patients who had withdrawn from the workforce before normal retirement age increased from 37 to 53 % over the 10-year period. Many of the measures used in the assessment of AS do not generally deteriorate over time in those with well-established disease. This suggests that deterioration may plateau in established disease. However, AS has a long-term social impact with levels of employment in this cohort 30 % lower than the general population. Interventions directed at preventing deterioration may be more effective earlier in their disease course, before this plateau is reached.

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.

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.

ObjectiveThere is great interest in the identification of genetic factors that differentiate psoriatic arthritis (PsA) from psoriasis vulgaris (PsV), as such discoveries could lead to the identification of distinct underlying aetiological pathways. Recent studies identified single nucleotide polymorphisms (SNPs) in the interleukin 13 (IL-13) gene region as risk factors for PsV. Further investigations in one of these studies found the effect to be primarily restricted to PsA, thus suggesting the discovery of a specific genetic risk factor for PsA. Given this intriguing evidence, association to this gene was investigated in large collections of PsA and PsV patients and healthy controls.MethodsTwo SNPs (rs20541 and rs1800925) mapping to the IL-13 gene were genotyped in 1057 PsA and 778 type I PsV patients using the Sequenom genotyping platform. Genotype frequencies were compared to those of 5575 healthy controls. Additional analyses were performed in phenotypic subgroups of PsA (type I or II PsV and in those seronegative for rheumatoid factor).ResultsBoth SNPs were found to be highly associated with susceptibility to PsA (rs1800925 ptrend = 6.1×10−5 OR 1.33, rs20541 ptrend = 8.0×10−4 OR 1.27), but neither SNP was significantly associated with susceptibility to PsV.ConclusionsThis study confirms that the effect of IL-13 risk locus is specific for PsA, thus highlighting a key biological pathway that differentiates PsA from PsV. The identification of markers that differentiate the two diseases raises the possibility in future of allowing screening of PsV patients to identify those at risk of developing PsA.