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Objectives To assess the impact on patient outcomes of the spondyloarthritis (SpA) and inflammatory bowel disease (IBD) multidisciplinary team (MDT) meetings in a large university hospital. Methods A single-centre retrospective observational case-note review was conducted assessing the outcome of all 226 cases discussed at the SpA–IBD MDT meetings in a large UK university hospital between 2017 and 2022. Results A total of 226 patients were discussed. It was deemed that 97% of MDT meetings helped to improve communication between teams, and 100% were educational. A total of 57% of discussions led to an instant change of disease management, while 40% of discussions resulted in a treatment plan that avoided the use of dual advanced therapy. This improved patient safety by reducing immunosuppression. The MDT meetings were highly cost and time efficient; 125 referrals between specialists were avoided, and in 51 cases there was a significant chance of reducing future drug costs. A timely investigation or appointment was arranged following 50% of MDT discussions, helping to clarify the diagnosis and optimize patient care. Nine percent of meetings enabled drugs to be prescribed to patients that are not yet licensed for the other speciality, thereby improving treatment options available in the management of complex cases. Conclusion The MDT meetings have been beneficial for patients, the clinical team and the institution. This approach might be considered by other rheumatology and gastroenterology departments. [ABSTRACT FROM AUTHOR]

Objectives Timely diagnosis remains a challenge in axial SpA (axSpA). In addition, data are scarce on the impact of diagnostic delay and disease progression in affected individuals. The British Axial Spondyloarthritis Inception Cohort (BAxSIC) study aims to investigate the impact of newly diagnosed axSpA, the natural history of the disease and the effect of diagnostic delay on disease outcomes. Methods BAxSIC is a prospective, multicentre, observational study. Eligible participants are adults (≥16 years of age), with a physician-confirmed diagnosis of axSpA in the 6 months prior to study entry, recruited from secondary and tertiary rheumatology centres in the UK. Participants will be followed up for 3 years, with in-person visits at baseline and 24 months. In addition, patient self-reported assessments will be recorded remotely via the online electronic case report form (eCRF) at 6, 12, 18, 30 and 36 months. Results The first patient was enrolled in BAxSIC in June 2023. Recruitment is currently ongoing and is planned to end in June 2026. Initial results will be available in 2027. Since opening, the trial has undergone two protocol amendments. Conclusion The BAxSIC study is the first inception cohort designed to investigate the impact of diagnostic delay on clinical presentation and long-term functional outcomes in patients with axSpA in the UK. With an innovative, patient-led virtual longitudinal data collection model, data generated from this study will help inform and improve the care of people newly diagnosed with axSpA. Trial registration ClinicalTrials.gov (http://clinicaltrials.gov), NCT05676775. [ABSTRACT FROM AUTHOR]

The authors highlight the tenth anniversary of the constitution of the British Society for Spondyloarthritis (BRITSpA), a group of United Kingdom-based professionals working together with the common aim of advancing knowledge of treatment of spondyloarthritis (SpA). They discuss the purpose of the establishment of BRITSpA, evidence of the success of BRITSpA in engaging the community, and one of the main achievements of BRITSpA.

Introduction: Diagnosis of axial spondyloarthritis (axSpA) is frequently delayed for years after symptom onset. However, little is known about patient and healthcare professional (HCP) perspectives on barriers and facilitators in axSpA diagnosis. This study explored the experiences and perceptions of both groups regarding the factors affecting the timely diagnosis of axSpA. Method: Semi-structured interviews with patients with axSpA and axSpA-interested HCPs from the United Kingdom (UK) were performed by telephone or Microsoft Teams and focussed on the individuals' perspective of the diagnostic journey for axSpA. Interview transcripts were thematically analysed. Results: Fourteen patients with axSpA (10 female, 4 male) and 14 UK based HCPs were recruited, the latter comprising of 5 physiotherapists, 4 General Practitioners, 3 rheumatologists, a nurse, and an occupational therapist. Barriers to diagnosis identified by patients and HCPs were: difficult to diagnose, a lack of awareness, unclear referral pathways, patient behaviour and patient/HCP communication. Patient-identified facilitators of diagnosis were patient advocacy, clear referral processes and pathways, increased awareness, and serendipity. HCPs identified promoting awareness as a facilitator of diagnosis, along with symptom recognition, improvements to healthcare practice and patient/HCP communications. Conclusion: Poor communication and a lack of understanding of axSpA in the professional and public spheres undermine progress towards timely diagnosis of axSpA. Improving communication and awareness for patients and HCPs, along with systemic changes in healthcare (such as improved referral pathways) could reduce diagnostic delay. [ABSTRACT FROM AUTHOR]

The objective of this study is to examine the contribution of pain catastrophising to Axial Spondyloarthritis (axSpA) patient's physical function and to test the mediating role of fear of movement, and uniquely, the contribution of competence frustration to the fear-avoidance model. Participants (N = 98, 70% female, M age = 45.62, SD 12.16) completed an online survey (December 2020–May 2021) distributed in the United Kingdom via the National Axial Spondyloarthritis Society (n ≈ 3500; NASS, 2019). The PROCESS SPSS macro was used to test three mediation models using percentile bootstrap 95% confidence intervals (PBCI). A significant indirect effect on the relationship between pain and physical function via fear of movement (β = 0.10, 95% PBCI = 0.030–0.183) was observed (Model 1). Model 2 showed the relationship between pain catastrophising and physical function to be significantly mediated by fear of movement (β = 0.16, 95% PBCI = 0.005–0.322). Finally, Model 3 showed a significant indirect effect on the relationship between pain catastrophising and physical function via competence frustration (β = 0.15, 95% PBCI = 0.014–0.309) but not through fear of movement (β = 0.062, 95% PBCI = − 0.134 to 0.248). To our knowledge, this is the first study to examine and demonstrate the unique contribution of competence need frustration to the Fear-avoidance model in people that live with axSpA. Identifying modifiable factors that contribute to disease outcomes such as physical function can improve the care and quality of life for people living with a disease currently without a cure. [ABSTRACT FROM AUTHOR]

Objective To investigate opioid prescribing trends and assess the impact of the COVID-19 pandemic on opioid prescribing in rheumatic and musculoskeletal diseases (RMDs). Methods Adult patients with RA, PsA, axial spondyloarthritis (AxSpA), SLE, OA and FM with opioid prescriptions between 1 January 2006 and 31 August 2021 without cancer in UK primary care were included. Age- and gender-standardized yearly rates of new and prevalent opioid users were calculated between 2006 and 2021. For prevalent users, monthly measures of mean morphine milligram equivalents (MME)/day were calculated between 2006 and 2021. To assess the impact of the pandemic, we fitted regression models to the monthly number of prevalent opioid users between January 2015 and August 2021. The time coefficient reflects the trend pre-pandemic and the interaction term coefficient represents the change in the trend during the pandemic. Results The study included 1 313 519 RMD patients. New opioid users for RA, PsA and FM increased from 2.6, 1.0 and 3.4/10 000 persons in 2006 to 4.5, 1.8 and 8.7, respectively, in 2018 or 2019. This was followed by a fall to 2.4, 1.2 and 5.9, respectively, in 2021. Prevalent opioid users for all RMDs increased from 2006 but plateaued or dropped beyond 2018, with a 4.5-fold increase in FM between 2006 and 2021. In this period, MME/day increased for all RMDs, with the highest for FM (≥35). During COVID-19 lockdowns, RA, PsA and FM showed significant changes in the trend of prevalent opioid users. The trend for FM increased pre-pandemic and started decreasing during the pandemic. Conclusion The plateauing or decreasing trend of opioid users for RMDs after 2018 may reflect the efforts to tackle rising opioid prescribing in the UK. The pandemic led to fewer people on opioids for most RMDs, providing reassurance that there was no sudden increase in opioid prescribing during the pandemic. [ABSTRACT FROM AUTHOR]

Background: Enthesitis is a key feature of spondyloarthropathy (SpA). In recent years, JAK inhibitors have emerged as efficacious drugs in the landscape of advanced therapies for patients with SpA. Method: The aim of this scoping literature review was to search the published literature for studies on JAK inhibitors and their effects on enthesitis in patients with SpA and evaluate the data and summarise the findings. The clinical trials reviewed used the Leeds Enthesitis Index, Spondyloarthritis Research Consortium of Canada Enthesitis Index, and Maastrich Ankylosing Spondylitis Enthesitis Score as outcome measures. Results: Tofacitinib, upadacitinib, and filgotinib had numerically greater reductions in the enthesitis scores when compared with placebo. Conclusion: While the JAK inhibitors are therapeutic options for enthesitis in SpA, head‐to‐head studies are needed to compare the JAK inhibitors against the biological drugs (targeting TNF, IL‐17, and IL‐12/23) as well as studies showing the effects of JAK inhibitors on enthesitis imaging. [ABSTRACT FROM AUTHOR]

Background: Axial Spondyloarthritis is an inflammatory disease associated with significant diagnostic delays. Steen et al. (2021) found inadequate consideration of axial Spondyloarthritis (axSpA) in physiotherapists back pain assessments. Since the previous survey, increased professional education on axSpA has occurred and First Contact Practitioners (FCPs), now widely established in General Practice, are key in supporting earlier recognition. Objectives: (1) To re‐evaluate physiotherapists' and evaluate FCPs' awareness, knowledge, and confidence in screening for and recognising features of axSpA and criteria prompting referral to rheumatology. (2) To compare these results to previous research (Steen et al., 2021). Design: As per Steen et al. (2021), an online survey was undertaken combining back pain vignettes (reflecting axSpA, non‐specific low back pain [NSLBP] and radicular syndrome) and questioning on features of suspected axSpA. Results: 165 surveys were analysed. Only 73% (n = 120/165) of respondents recognised the axSpA vignette compared to NSLBP 91% (n = 80/88) and radicular syndrome 88% (n = 68/77). An improvement in axSpA recognition was demonstrated compared with previous data. FCPs performed slightly better with 77% (n = 67/87) of respondents recognising the axSpA vignette. Adequate awareness of national referral guidance was evident in only 55% of 'clinical reasoning' and 6% of 'further subjective screening' responses. There was still misplaced confidence in recognising clinical features of axSpA compared to knowledge levels shown, including high importance given to inflammatory markers. Conclusion(s): Musculoskeletal physiotherapists demonstrate some improved knowledge and awareness of axSpA compared with previous study findings. Consideration of axSpA is still not universal in musculoskeletal physiotherapists' or FCPs' approaches to persistent back pain assessments and awareness of national referral guidance remains limited. This study highlights the continued need for professional education. Enhanced knowledge of screening and referral criteria in musculoskeletal clinical practice would support earlier diagnosis and better outcomes. [ABSTRACT FROM AUTHOR]

The aim was to study the genetic correlation and causal relationship between spondyloarthritis (SpA) and blood metabolites based on the large-scale genome-wide association study (GWAS) summary data. The GWAS summary data (3966 SpA and 448,298 control cases) of SpA were from the UK Biobank, and the GWAS summary data (486 blood metabolites) of human blood metabolites were from a published study. First, the genetic correlation between SpA and blood metabolites was analyzed by linkage disequilibrium score (LDSC) regression. Next, we used Mendelian randomization (MR) analysis to perform access causal relationship between SpA and blood metabolites. Random effects inverse variance weighted (IVW) was the main analysis method, and the MR Egger, weighted median, simple mode, and weighted mode were supplementary methods. The MR analysis results were dominated by the random effects IVW. The Cochran's Q statistic (MR-IVW) and Rucker's Q statistic (MR Egger) were used to check heterogeneity. MR Egger and MR pleiotropy residual sum and outlier (MR-PRESSO) were used to check horizontal pleiotropy. The MR-PRESSO was also used to check outliers. The "leave-one-out" analysis was used to assess whether the MR analysis results were affected by a single SNP and thus test the robustness of the MR results. Finally, we identified seven blood metabolites that are genetically related to SpA: X-10395 (correlation coefficient = −0.546, p = 0.025), pantothenate (correlation coefficient = −0.565, p = 0.038), caprylate (correlation coefficient = −0.333, p = 0.037), pelargonate (correlation coefficient = −0.339, p = 0.047), X-11317 (correlation coefficient = −0.350, p = 0.038), X-12510 (correlation coefficient = −0.399, p = 0.034), and X-13859 (Correlation coefficient = −0.458, p = 0.015). Among them, X-10395 had a positive genetic causal relationship with SpA (p = 0.014, OR = 1.011). The blood metabolites that have genetic correlation and causal relationship with SpA found in this study provide a new idea for the study of the pathogenesis of SpA and the determination of diagnostic indicators. [ABSTRACT FROM AUTHOR]

Background: Axial spondyloarthritis (axSpA) is an inflammatory disease associated with significant diagnostic delays and is commonly missed in assessments of persistent back pain. Objective: To explore musculoskeletal physiotherapists' awareness, knowledge and confidence in screening for signs, symptoms and risk factors of suspected axSpA and criteria for rheumatology referral. Design: An online UK survey was undertaken combining back pain vignettes (reflecting axSpA, non‐specific back pain and radicular syndrome) and questioning on features of suspected axSpA. Recruitment utilised online professional forums and social media. Data analysis included descriptive statistics and conceptual content analysis for free text responses. Results: 132 survey responses were analysed. Only 67% (88/132) of respondents identified inflammatory pathologies as a possible cause of persistent back pain. Only 60% (79/132) recognised the axSpA vignette compared to non‐specific low back pain (94%) and radicular syndrome (80%). Most suspecting axSpA would refer for specialist assessment (77/79; 92%). Awareness of national referral guidance was evident in only 50% of 'clinical reasoning' and 20% of 'further subjective screening' responses. There was misplaced confidence in recognising clinical features of axSpA (≥7/10) compared to knowledge levels shown, including high importance given to inflammatory markers and human leucocyte antigen B27 (median = 8/10). Conclusions: Musculoskeletal physiotherapists may not be giving adequate consideration to axSpA in back pain assessments. Awareness of national referral guidance was also limited. Professional education on screening and referral for suspected axSpA is needed to make axSpA screening and referral criteria core knowledge in musculoskeletal clinical practice, supporting earlier diagnosis and better outcomes. [ABSTRACT FROM AUTHOR]

The article offers information on the British Society for Spondyloarthritis (BRITSpA), which was established in 2015 to facilitate the sharing of information and networking among members of the various medical and scientific disciplines associated with spondyloarthritis (SPA). Topics covered include BRITSpA's membership as of 2020, its commitment to education and research, and its collaboration with national and international groups.

Objective To quantify the extent to which co-morbid FM is associated with higher disease activity, worse quality of life (QoL) and poorer response to TNF inhibitors (TNFis) in patients with axial SpA. Methods A prospective study recruiting across 83 centres in the UK. Clinical information and patient-reported measures were available, including 2011 criteria for FM. Multivariable linear regression was used to model the effect of meeting the FM criteria on disease activity, QoL and response to TNFis. Results A total of 1757 participants were eligible for analyses, of whom 22.1% met criteria for FM. Those with co-morbid FM criteria had higher disease activity [BASDAI average difference FM+ − FM− 1.04 (95% CI 0.75, 1.33)] and worse QoL [Ankylosing Spondylitis Quality of Life score difference 1.42 (95% CI 0.88, 1.96)] after adjusting for demographic, clinical and lifestyle factors. Among 291 participants who commenced biologic therapy, BASDAI scores in those with co-morbid FM were 2.0 higher at baseline but decreased to 1.1 higher at 12 months. There was no significant difference in the likelihood of meeting Assessment of SpondyloArthritis international Society 20 criteria at 12 months. Less improvement in disease activity and QoL over 3 months of TNFi therapy was most strongly related to high scores on the FM criteria symptom severity scale component. Conclusion Fulfilling criteria for FM has a modest impact on the assessment of axial SpA disease activity and QoL and does not significantly influence response to biologic therapy. Those with a high symptom severity scale on FM assessment may benefit from additional specific management for FM. [ABSTRACT FROM AUTHOR]

The spondyloarthropathies are an heterogenous group of inflammatory conditions with a diverse phenotype and multiple clinical manifestations involving joints, entheses, spine, skin and other tissues. Diagnosis is often delayed after symptom onset leading to significant disability and reduced quality of life in affected individuals. Emphasis therefore is given to informing and educating patients about their disease, treatment options and how to manage disease flares. These are some of the points collected in the National Institute of Health and Care Excellence (NICE) guidelines published in February of 2017 to alert Health professionals about these group of diseases. The guidelines highlight why it is important to be able to refer to a rheumatologist, as well as describing when a referral should be made. It also includes information on diagnosis, treatment, education, and an agenda for research. Since a significant number of people affected with these conditions, in particular those suffering from psoriatic arthritis are likely to be seen in the context of the dermatology clinic, the dermatology nurse may play an active part of this process. [ABSTRACT FROM AUTHOR]

Objectives. A national audit was performed assessing the early management of suspected inflammatory arthritis by English and Welsh rheumatology units. The aim of this audit was to measure the performance of rheumatology services against National Institute for Health and Care Excellence (NICE) quality standards (QSs) for the management of early inflammatory arthritis benchmarked to regional and national comparators for the first time in the UK. Methods. All individuals >16 years of age presenting to rheumatology services in England and Wales with suspected new-onset inflammatory arthritis were included in the audit. Information was collected against six NICE QSs that pertain to early inflammatory arthritis management. Results. We present national data for the 6354 patients recruited from 1 February 2014 to 31 January 2015; 97% of trusts and health boards in England and Wales participated in this audit. Only 17% of patients were referred by their general practitioner within 3 days of first presentation. Specialist rheumatology assessment occurred within 3 weeks of referral in 38% of patients. The target of DMARD initiation within 6 weeks of referral was achieved in 53% of RA patients; 36% were treated with combination DMARDs and 82% with steroids within the first 3 months of specialist care. Fifty-nine per cent of patients received structured education on their arthritis within 1 month of diagnosis. In total, 91 % of patients had a treatment target set; the agreed target was achieved within 3 months of specialist review in only 27% of patients. Access to urgent advice via a telephone helpline was reported to be available in 96% of trusts. Conclusion. The audit has highlighted gaps between NICE standards and delivery of care, as well as substantial geographic variability. [ABSTRACT FROM AUTHOR]

Objective. To determine feasibility of TNF inhibitor (TNFi) dose reduction for severe AS and PsA patients. Methods. A retrospective study in a real-world setting. Criteria for dose reduction of TNFi included BASDAI <4 for ≥6 months in AS; or DAS28-ESR ≤ 3.2 for ≥6 months in PsA. TNFi dose was reduced by one-third. Patients who flared (BASDAI > 4 in AS or DAS28-ESR > 3.2 in PsA) were re-escalated to standard treatment dose. Results. Twenty-six per cent (33/125) of AS and 18% (15/83) of PsA patients fulfilled criteria and underwent TNFi dose reduction. Fifty-eight per cent (19/33) of AS and 60% (9/15) of PsA patients maintained TNFi dose reduction for mean (S.D.) of 1.0 (0.8) years. Reinstating standard dose of TNFi recaptured low disease activity in all patients who failed dose reduction within 24 weeks, with no statistically significant difference in mean BASDAI compared with those maintaining TNFi dose reduction in AS at 24 weeks [mean (S.D.) BASDAI 2.4 (1.1) vs 1.9 (1.5), respectively (P = 0.229)]; however in PsA, those who failed dose reduction had higher disease activity compared with patients maintained on TNFi dose reduction at 24 weeks [mean (S.D.) DAS28-ESR 2.7 (0.6) vs 1.3 (0.5), respectively (P ≤ 0.001)]. In PsA, a lower DAS28-ESR prior to dose reduction of TNFi was associated with more successful dose reduction. Conclusions. In a real-world setting, 60% of individuals with severe AS and PsA who achieve low disease activity can successfully reduce the dose of TNFi therapy by a third for a mean of 1 year. [ABSTRACT FROM AUTHOR]

Background: Axial spondyloarthropathy typically has its onset in early adulthood and can impact significantly on quality of life. In the UK, biologic anti-tumour necrosis factor therapy is recommended for patients who are unresponsive to non-steroidal anti-inflammatory drugs. There remain several unresolved issues about the long-term safety and quality of life outcomes of biologic treatment in axial spondyloarthropathy. Long-term "real-world" surveillance data are required to complement data from randomised controlled trials.Methods/design: We are conducting a UK-wide prospective cohort study of patients with axial spondyloarthropathy who are naïve to biologic therapy at the time of recruitment. Those about to commence anti-tumour necrosis factor biologic therapy will enter a "biologic" sub-cohort with other patients assigned to a "non-biologic" sub-cohort. The primary objective is to determine whether the use of biologic therapy is associated with an increased risk of serious infection, while secondary objectives are to assess differences in malignancy, serious comorbidity, all-cause mortality but also assess impact on specific clinical domains (physical health, mental health and quality of life) including work outcomes between biologic and non-biologic patient cohorts. Patients will be followed-up for up to 5 years. Data are obtained at baseline and at standard clinical follow-up visits - at 3, 6 and 12 months and then annually for the biologic cohort and annually for the non-biologic cohort. This study will also collect biological samples for genetic analysis.Discussion: Although biologic therapy is widely used for ankylosing spondylitis patients who are unresponsive to non-steroidal anti-inflammatory drugs, the majority of the available safety information comes from rheumatoid arthritis, where increased infection risk has consistently been shown. However, given the typical demographic differences between rheumatoid arthritis and axial spondyloarthropathy patients, it is important to develop an epidemiologically rigorous cohort of patients receiving biologic therapy to effectively evaluate outcomes with regard not only to safety but also to quantify benefits across clinical, psychosocial and work outcomes.Clinical Trial Registration: This is an observational cohort study and clinical trial registration was not required or obtained. [ABSTRACT FROM AUTHOR]

Objective. To explore severe flare and constant disease pattern (no periods of remission) in AS as predictors of poor outcomes [impaired function, unemployment/early retirement, work impairment, anti-TNF, surgery, frequent general practitioner (GP) visits, depression and anxiety]. Methods. Three hundred and forty-eight AS patients completed questionnaires about their experience with disease flares. Questionnaire data were linked to electronic medical records to examine visits to GPs and hospital admission data. Outcomes were stratified in two ways: self-reported experience of severe flare and constant disease pattern using the flare illustration tool. Results. The majority of patients (72%, 208/289) experienced flare pre-diagnosis. Severe flares were reported by 58% (202/348) of participants (self-report); of these, 195 responded about earliest flares and 69% (135/195) of severe flare patients experienced flares pre-diagnosis. Patients who self-reported severe flares had worse function, disease activity, work impairment and symptoms of anxiety and depression, were less likely to be employed and had more GP encounters per year compared with those who never reported severe flares. Participants who reported constant unremitting disease on the flare illustration tool had worse disease activity, impaired function and work impairment and were more likely to smoke compared with those with intermittent disease. Analysis showed a relationship between self-report of severe flare and subsequent depression, impaired function, increased disease activity and work limitations. Conclusion. Severe flare is associated with poor outcomes such as work impairment and impaired function. The onset of severe flare early in the disease course may be a risk factor for later poor outcome and this group could benefit from targeted early aggressive treatment to improve prognosis. [ABSTRACT FROM AUTHOR]

The article presents abstracts of studies on spondyloarthropathies which include the efficacy of apremilast in patients with psoriatic arthritis, the ethnic differences in the response to anti-tumor necrosis factor (TNF) and the impact of fatigue on activity levels.

In February, NICE published its first clinical guideline on spondyloarthritis in adults (NG65). This article provides a short summary of the guidance. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objective HLA-B27 and endoplasmic reticulum aminopeptidase 1 (ERAP1) are the two strongest genetic factors predisposing to ankylosing spondylitis (AS). A key aminopeptidase in class I major histocompatibility complex presentation, ERAP1 potentially contributes to the pathogenesis of AS by altering HLA-B27 peptide presentation. The aim of this study was to analyze the effects of ERAP1 on the HLA-B27 peptide repertoire and peptide presentation to cytotoxic T lymphocytes (CTLs). Methods ERAP1-silenced and -competent HeLa.B27 and C1R.B27 cells were isotope-labeled, mixed, lysed, and then immunoprecipitated using W6/32 or ME1 antibodies. Peptides bound to HLA-B27 were eluted and analyzed by tandem mass spectrometry. Selected peptides were synthesized and tested for HLA-B27 binding ability. The effect of ERAP1 silencing/mutation on presentation of an immunodominant viral HLA-B27 epitope, KK10, to CTLs was also studied. Results In both HeLa.B27 and C1R.B27 cells, the proportion of 9-mer HLA-B27-bound peptides was decreased by ERAP1 silencing, whereas the percentages of longer peptides (11-13 mer) were increased. Surprisingly, following ERAP1 silencing, C-terminally extended peptides were readily identified. These were better able to bind to HLA-B27 than were N-terminally extended peptides lacking an arginine at position 2. In both HeLa.B27 cells and mouse fibroblasts expressing HLA-B27, the absence of ERAP1 reduced peptide recognition by HLA-B27-restricted KK10-specific CTLs following infection with recombinant vaccinia virus or transfection with minigenes expressing KK10 precursors. Presence of an AS-protective variant of ERAP1, K528R, as compared to wild-type ERAP1, reduced the peptide recognition by KK10 CTLs following transfection with extended KK10 minigenes. Conclusion These results show that ERAP1 directly alters peptide binding and presentation by HLA-B27, thus demonstrating a potential pathogenic mechanism in AS. Inhibition of ERAP1 could potentially be used for treatment of AS and other ERAP1-associated diseases. [ABSTRACT FROM AUTHOR]

Objective. Inflammatory back pain (IBP) is the earliest and most common symptom of axial SpA. However, there is very little information about the prevalence of IBP in the UK. In this cross-sectional cohort study we examined the prevalence of IBP in a UK primary care population using three published IBP criteria.Methods. Potential participants aged 18–80 years were identified from the records of a large general practice in Norfolk, UK, with 17 177 patients. Read codes were used to identify those who had consulted their general practitioner on at least one occasion with back pain. A self-completed screening questionnaire was sent to a sample of 978 patients, enquiring about symptoms of IBP and extra-spinal manifestations of SpA. Questionnaire responses were used to determine whether patients met the Assessment of SpondyloArthritis international Society (ASAS), Calin and Berlin IBP criteria.Results. Five hundred and five completed questionnaires were returned (response rate 51.6%). The median age of respondents was 60 years [interquartile range (IQR) 48–67] and 44.8% were male. The minimum prevalence of IBP among patients with at least one previous consultation for back pain was 7.7% (95% CI 6.2, 9.5) using the ASAS criteria, 13.5% (11.5, 15.8) using the Calin criteria and 15.4% (13.3, 17.8) using the Berlin criteria. There was no significant difference in prevalence between men and women, and between different age groups. Extrapolated to the practice population as a whole, the minimum prevalence of IBP in a UK primary care population is 1.7–3.4%.Conclusion. The prevalence of IBP varies significantly depending on the criteria used for classification. [ABSTRACT FROM PUBLISHER]

Objectives. HLA-B*27:05 is associated with AS whereas HLA-B*27:09 is not associated. We hypothesized that different interactions with KIR immune receptors could contribute to the difference in disease association between HLA-B*27:05 and HLAB*27:09. Thus, the objective of this study was to compare the formation of β2m-free heavy chain (FHC) including B27 dimers (B272) by HLA-B*27:05 and HLA-B*27:09 and their binding to KIR immunoreceptors.Methods. We studied the formation of HLA-B*27:05 and HLA-B*27:09 heterotrimers and FHC forms including dimers in vitro and in transfected cells. We investigated HLA-B*27:05 and HLA-B*27:09 binding to KIR3DL1, KIR3DL2 and LILRB2 by FACS staining with class I tetramers and by quantifying interactions with KIR3DL2CD3ɛ-reporter cells and KIR3DL2-expressing NK cells. We also measured KIR expression on peripheral blood NK and CD4 T cells from 18 HLA-B*27:05 AS patients, 8 HLA-B27 negative and 12 HLA-B*27:05+ and HLA-B*27:09+ healthy controls by FACS staining.Results. HLA-B*27:09 formed less B272 and FHC than HLA-B*27:05. HLA-B*27:05-expressing cells stimulated KIR3DL2CD3ɛ-reporter T cells more effectively. Cells expressing HLA-B*27:05 promoted KIR3DL2+ NK cell survival more strongly than HLA-B*27:09. HLA-B*27:05 and HLA-B*27:09 dimer tetramers stained KIR3DL1, KIR3DL2 and LILRB2 equivalently. Increased proportions of NK and CD4 T cells expressed KIR3DL2 in HLA-B*27:05+ AS patients compared with HLA-B*27:05+, HLA-B*27:09+ and HLA-B27− healthy controls.Conclusion. Differences in the formation of FHC ligands for KIR3DL2 by HLA-B*27:05 and HLA-B*27:09 could contribute to the differential association of these alleles with AS. [ABSTRACT FROM PUBLISHER]

Objective. Spinal mobility is assessed frequently in patients with AS/axial SpA using the BASMI to provide baseline measurement and monitor change over time. The interpretation of BASMI scores has been hindered by the absence of normative values. We aimed to obtain normative values for the BASMI in healthy men and women in a UK population.Methods. A cross-sectional study of 168 volunteers stratified by gender and age was completed. Exclusion criteria comprised factors potentially influencing spinal mobility. Each component of the BASMI was assessed, with the total score computed using the 10-point scoring system. Measurements were taken by physiotherapists following an agreed protocol. Data were summarized and analysed with age-specific centiles and CIs calculated.Results. Total BASMI scores ranged from 0 to 4.4, with only 1.2% of the sample having a score of 0. The estimated median score for an individual age 25 years was 0.9, increasing with age to 2.1 for an individual age 65 years. There was a corresponding increase in component BASMI scores, which was more pronounced for some components than others.Conclusion. Our data indicate that it is unusual for healthy individuals to score zero on the BASMI, which has implications for the interpretation of scores, especially at baseline. The generation of normative values has the potential to inform clinical assessment of spinal mobility and assist patients in understanding how their spinal mobility compares with that of a healthy age-matched population. [ABSTRACT FROM PUBLISHER]

Objective Spondylarthritides (SpA), including ankylosing spondylitis (AS), are common inflammatory rheumatic diseases that are strongly associated with positivity for the HLA class I allotype B27. HLA-B27 normally forms complexes with β2-microglobulin (β2m) and peptide to form heterotrimers. However, an unusual characteristic of HLA-B27 is its ability to form β2m-free heavy chain homodimers (HLA-B272), which, unlike classic HLA-B27, bind to killer cell immunoglobulin-like receptor 3DL2 (KIR-3DL2). Binding of HLA-B272 to KIR-3DL2-positive CD4+ T and natural killer (NK) cells stimulates cell survival and modulates cytokine production. This study was undertaken to produce an antibody to HLA-B272 in order to confirm its expression in SpA and to inhibit its proinflammatory properties. Methods We generated monoclonal antibodies by screening a human phage display library positively against B272 and negatively against B27 heterotrimers. Specificity was tested by enzyme-linked immunosorbent assay (ELISA), surface plasmon resonance (SPR) assay, and fluorescence-activated cell sorting (FACS) analysis of B272-expressing cell lines and peripheral blood mononuclear cells (PBMCs) and synovial fluid mononuclear cells (SFMCs) from patients with SpA. Functional inhibition of KIR-3DL2-B272 interactions was tested using cell lines and PBMCs from patients with SpA. Results Monoclonal antibody HD6 specifically recognized recombinant HLA-B272 by ELISA and by SPR assay. HD6 bound to cell lines expressing B272. FACS revealed binding of HD6 to PBMCs and SFMCs from patients with AS but not from controls. HD6 inhibited both the binding of HLA-B272 to KIR-3DL2 and the survival and proliferation of KIR-3DL2-positive NK cells. Finally, HD6 inhibited production of the proinflammatory disease-associated cytokine interleukin-17 by PBMCs from patients with AS. Conclusion These results demonstrate that antibody HD6 has potential for use in both the investigation and the treatment of AS and other B27-associated spondylarthritides. [ABSTRACT FROM AUTHOR]

Objective In rats transgenic for human HLA-B27 and β2-microglobulin (B27-transgenic rats), colitis and peripheral inflammation develop spontaneously. Therefore, B27-transgenic rats provide a model of spondylarthritis. Because inflammation in these rats requires CD4+ T lymphocytes and involves intestinal pathology, we hypothesized that dendritic cells (DCs) that migrate from the intestine and control CD4+ T cell differentiation would be aberrant in B27-transgenic rats. Methods Migrating intestinal lymph DCs were collected via thoracic duct cannulation from B27-transgenic and control (HLA-B7-transgenic or nontransgenic) rats. The phenotypes of these DCs and of mesenteric lymph node DCs were assessed by flow cytometry. The ability of DCs to differentiate from bone marrow precursors in vitro was also assessed. Results Lymph DCs showed increased activation and, strikingly, lacked the specific DC population that is important for maintaining tolerance to self-antigens. This population of DCs was also depleted from the mesenteric lymph nodes of B27-transgenic rats. Furthermore, in vitro culture of DCs from bone marrow precursors revealed a defect in the ability of B27-transgenic rats to produce DCs of the migratory phenotype, although the DCs that were generated induced enhanced interleukin-17 (IL-17) production from naive CD4+ T cells. Conclusion We describe 2 different mechanisms by which HLA-B27 may contribute to inflammatory disease: increased apoptotic death of B27-transgenic DCs that normally function to maintain immunologic tolerance and enhanced IL-17 production from CD4+ T cells stimulated by the surviving B27-transgenic DCs. [ABSTRACT FROM AUTHOR]

Objective To assess the sensitivity and specificity of the Classification of Psoriatic Arthritis (CASPAR) Study Group criteria in early psoriatic arthritis (PsA) and to compare them with the sensitivity and specificity of the Moll and Wright criteria. Methods The CASPAR Study Group criteria were applied to patients with early PsA (<24 months symptom duration) and to control patients with other new-onset inflammatory arthritides. Both groups were naive to all disease-modifying antirheumatic drugs. The gold standard diagnosis was confirmed by the consulting rheumatologist using radiography and magnetic resonance imaging where required. Proportions of patients and control patients meeting the criteria were compared using McNemar's tests. Results We recruited a total of 111 patients with early PsA and 111 control patients with other forms of inflammatory arthritis (82 with rheumatoid arthritis, 13 with undifferentiated arthritis, 9 with spondylarthritis, 4 with inflammatory osteoarthritis, and 3 with crystal arthritis) to the study. The sensitivity of the CASPAR Study Group criteria in classifying early PsA was 87.4% compared to 80.2% for the Moll and Wright criteria. The specificity for both criteria was 99.1%. When considering different cut points for the CASPAR Study Group criteria, the best cut point for classification remained a score of ≥3 as in the original CASPAR Study Group analysis. Considering a score of ≥2 gave a higher sensitivity of 99.1% but resulted in a drop in specificity to 94.6%. Regression analysis determined that psoriasis and rheumatoid factor negativity were the most important features that differentiated PsA, followed by nail psoriasis and current or previous dactylitis. Conclusion The CASPAR Study Group criteria are more sensitive than the Moll and Wright criteria in classifying early PsA. Although their sensitivity for early PsA is lower than that for established disease, the CASPAR Study Group criteria are valid for use as inclusion criteria for trials in early PsA. [ABSTRACT FROM AUTHOR]

Objective. Bone marrow oedema (BMO) and HLA-B27 are poor prognostic factors in axial SpA, and psoriasis is a poor prognostic factor in small-joint polyarthropathy. The aim of this study was to investigate the influence of HLA-B27, MRI BMO and psoriasis on long-term outcomes in early SpA-related knee joint oligoarthritis.Methods. Patients with SpA-related oligoarthritis with knee involvement were recruited. Baseline assessment included ESSG criteria, RF, HLA-B27 and MRI. The degree of MRI BMO was determined on fat-suppression sequences and scored using the whole-organ magnetic resonance imaging score (WORMS) (range 0–45). Patients were treated at the discretion of their rheumatologist and followed up for 10 years. Outcome assessments included joint counts, functional and symptomatic questionnaire, CRP and radiographic assessment for OA.Results. Forty-four patients were recruited [mean age 32 years (range 15–59 years), 70% male] with a mean disease duration at baseline of 9.75 months (1–48 months). Twenty-six (59%) patients (mean age 43 years, 65% male) returned for follow-up after a mean of 10 years (range 8.4–12.6 years). Ten (38%) patients had persistent clinical synovitis and 31% of knees had secondary radiographic OA. Global outcome was poor/very poor in 69% of cases. The only factor predicting outcome at 10 years was psoriasis, but neither HLA-B27 nor BMO. PsA patients had significantly worse global outcome compared with ReA (P = 0.036), and significantly worse symptomatic (P = 0.001) and functional (P = 0.001) outcome compared with other subtypes.Conclusion. SpA-related knee joint oligoarthritis has significant long-term clinical and radiological morbidity despite standard treatments. HLA-B27 and MRI BMO were not predictors of poor outcome as they are in axial SpA; however, the presence of psoriasis predicted significantly worse outcome. [ABSTRACT FROM PUBLISHER]

Objective. To determine the responsiveness and minimal important change (MIC) of Evaluation of Ankylosing Spondylitis Quality of Life (EASi-QoL), a reliable and valid patient-reported measure of AS-specific quality of life with four domains: physical function (PF), disease activity (DA), emotional well-being (EWB) and social participation (SP).Methods. A total of 1000 UK AS patients received a postal questionnaire including EASi-QoL. Comparative responsiveness of EASi-QoL was assessed against measures reflecting similar health domains in patients self-reporting an improvement in their AS-specific health at 6 months on a health transition question. Effect size (ES) statistics were calculated for all measures and MIC was determined for EASi-QoL. Comparative responsiveness was determined in a randomized trial of AS patients receiving etanercept (ETN) 50 mg weekly or SSZ 3 g daily.Results. Of 470 patients, 80 responding at 6 months reported health improvement. Responsiveness (ES) for EASi-QoL domains was superior or similar to comparator measures: DA 0.72 vs BASDAI 0.58; SP 0.52 vs SF-36 social functioning 0.29; PF 0.32 vs BASFI 0.28 and SF-36 PF 0.24; EWB 0.40 vs HADS-anxiety 0.13, HADS-depression 0.21 and SF-36 mental health 0.35. ES for the ASQoL was 0.40. Superior ES was seen in those improving somewhat. In the randomized trial, all EASi-QoL domains had superior responsiveness to comparator measures following ETN treatment. Following SSZ treatment, all EASi-QoL domains were highly responsive, but BASDAI and BASFI was more responsive than EASi-QoL(DA) and (PF), respectively.Conclusion. In patients reporting improvement during routine clinical practice or following treatment with ETN or SSZ, EASi-QoL domains have superior or comparable responsiveness than comparable measures. [ABSTRACT FROM PUBLISHER]

The article presents the results of a study on delay to diagnosis in axial spondyloarthritis (SpA) in the British healthcare system. Topics covered include how the 2009 Assessment of SpondyloArthritis International Society classification criteria for axial SpA formally recognized the utility of magnetic resonance imaging (MRI) in diagnosis and how the study found that delay to diagnosis has not yet improved and continues to be a huge challenge for patients with axial SpA.

The article presents abstracts of studies on imaging in rheumatology which include the diagnostic protocol for giant cell arteritis (GCA), the use of sonoelastography in spondyloarthropathy and the benefit of tenosynovitis in predicting early rheumatoid arthritis.