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Objectives To describe the prevalence and clinical associations of autoantibodies to a novel autoantigen, eukaryotic initiation factor 3 (eIF3), detected in idiopathic inflammatory myositis. Methods Sera or plasma from 678 PM patients were analysed for autoantigen specificity by radio-labelled protein immunoprecipitation (IPP). Samples immunoprecipitating the same novel autoantigens were further analysed by indirect immunofluorescence and IPP using pre-depleted cell extracts. The autoantigen was identified through a combination of IPP and MALDI-TOF mass spectrometry, and confirmed using commercial antibodies and IPP-western blots. Additional samples from patients with DM (668), DM-overlap (80), PM-overlap (191), systemic sclerosis (150), systemic lupus erythematosus (200), Sjogren’s syndrome (40), rheumatoid arthritis (50) and healthy controls (150) were serotyped by IPP as disease or healthy controls. Results IPP revealed a novel pattern in three PM patients (0.44%) that was not found in disease-specific or healthy control sera. Indirect immunofluorescence demonstrated a fine cytoplasmic speckled pattern for all positive patients. Mass spectrometry analysis of the protein complex identified the target autoantigen as eIF3, a cytoplasmic complex with a role in the initiation of translation. Findings were confirmed by IPP-Western blotting. The three anti-eIF3-positive patients had no history of malignancy or interstitial lung disease, and had a favourable response to treatment. Conclusion We report a novel autoantibody in 0.44% of PM patients directed against a cytoplasmic complex of proteins identified as eIF3. Although our findings need further confirmation, anti-eIF3 appears to correlate with a good prognosis and a favourable response to treatment.

Social Impact Bonds (SIBs) are a novel financing mechanism for public services delivery. This special issue about SIBs in the UK argues that they necessitate closer examination to understand the implications for all stakeholders. This introductory paper critically explores and challenges dominant practitioner narratives of SIBs as “win-win” solutions for governments and service providers. While SIBs may foster innovation it is unclear if they deliver better value given the complexity of public services. SIBs are a strategically ambiguous policy tool and policymakers should be cautious about SIBs due to contractual complexity and issues with ethics, governance, accountability and transparency.

One response to the major societal challenge of financial exclusion in the United Kingdom (UK) is microcredit lending for enterprise. Typically delivered via Community Development Finance Institutions (CDFIs) in the UK, these lending institutions can be conceptualised as ‘alternative’ economic spaces. Yet the nature of their alterity is unclear as categorisations of alternative-oppositional or alternative-substitute institutions are possible and could also be influenced by complexities in the UK relating to the welfare system and sustainability. Alterity is rarely static, being influenced by policies and regulation, and the nature of institutions’ alterity could have consequences for wellbeing, as different values and ideals underpin different conceptions of alterity which affect how these institutions operate. In this paper, the complexities of microcredit for enterprise lending within the UK are explored through in-depth interviews with UK ‘supply-side’ stakeholders. Conceptions of alterity are then used as an analytic lens to examine these results. Results suggest that these lenders remain in opposition to the mainstream as the needs of low-income individuals are embedded within their operating model. Microcredit lending is conceptualised in terms of responsible lenders offering fair credit to financially-excluded individuals using relationship banking practices. Such a conceptualisation provides a touchstone against which to assess shifts in lenders’ alterity and a platform from which to introduce legislative and regulatory changes to protect these ‘alternative-oppositional’ economic spaces. This paper begins to outline these responses that could help to ensure and grow a more community-engaged and varied local financial infrastructure within the UK.

Despite a lack of evidence of their effectiveness there is increasing enthusiasm for Social Impact Bonds (SIBs) from diverse political perspectives across the world. This paper argues that while SI...

Background Health inequalities in the UK have proved to be stubborn, and health gaps between best and worst-off are widening. While there is growing understanding of how the main causes of poor health are perceived among different stakeholders, similar insight is lacking regarding what solutions should be prioritised. Furthermore, we do not know the relationship between perceived causes and solutions to health inequalities, whether there is agreement between professional stakeholders and people living in low-income communities or agreement within these groups. Methods Q methodology was used to identify and describe the shared perspectives (‘subjectivities’) that exist on i) why health is worse in low-income communities (‘Causes’) and ii) the ways that health could be improved in these same communities (‘Solutions’). Purposively selected individuals (n = 53) from low-income communities (n = 25) and professional stakeholder groups (n = 28) ranked ordered sets of statements – 34 ‘Causes’ and 39 ‘Solutions’ – onto quasi-normal shaped grids according to their point of view. Factor analysis was used to identify shared points of view. ‘Causes’ and ‘Solutions’ were analysed independently, before examining correlations between perspectives on causes and perspectives on solutions. Results Analysis produced three factor solutions for both the ‘Causes’ and ‘Solutions’. Broadly summarised these accounts for ‘Causes’ are: i) ‘Unfair Society’, ii) ‘Dependent, workless and lazy’, iii) ‘Intergenerational hardships’ and for ‘Solutions’: i) ‘Empower communities’, ii) ‘Paternalism’, iii) ‘Redistribution’. No professionals defined (i.e. had a significant association with one factor only) the ‘Causes’ factor ‘Dependent, workless and lazy’ and the ‘Solutions’ factor ‘Paternalism’. No community participants defined the ‘Solutions’ factor ‘Redistribution’. The direction of correlations between the two sets of factor solutions – ‘Causes’ and ‘Solutions’ – appear to be intuitive, given the accounts identified. Conclusions Despite the plurality of views there was broad agreement across accounts about issues relating to money. This is important as it points a way forward for tackling health inequalities, highlighting areas for policy and future research to focus on. Electronic supplementary material The online version of this article (10.1186/s12913-019-3884-9) contains supplementary material, which is available to authorized users.

Background/Aims SLE is heterogeneous in clinical presentation, underlying immunology, and response to therapy. Patients with severe or resistant disease receive cyclophosphamide or rituximab. Although effective, late use of these therapies entails cumulative damage. Emerging predictors of response to rituximab include demographics, IFN-Scores and autoantibodies. For such predictors to change treatment strategy we need to understand their association with the effectiveness of other therapeutic options at earlier decision points. Prospective studies of treatment pathways are difficult to perform, requiring large populations followed for many years. We therefore investigated this question by analysing retrospective treatment pathways since diagnosis in patients whose biomarker status is subsequently known. Methods In patients with established SLE, attending Leeds SLE clinic, we collected demographics, clinical characteristics and blood at a single timepoint. Two previously validated IFN-Scores (IFN-Score A and IFN-Score B) were measured using Taqman. Autoantibodies were measured using immunoprecipitation. Treatment history covering all antimalarials, oral and intravenous immunosuppressants (agent, start and stop dates and reasons) since diagnosis was collected. Univariable and multivariable Cox proportional hazards models were used to test variables as predictors of the primary endpoint: time to cyclophosphamide/rituximab. Results 124 patients were included. Follow up since diagnosis was Median (IQR) 37.5 (27.4-52.3) years, total therapies per patient was 3 (1-4), therapies per year was 0.2 (0.1-0.3). 54/124 (44%) patients required cyclophosphamide/rituximab. Results of Cox regression are shown in the table. There was a significant association between high expression of IFN-Score B and requirement for cyclophosphamide/rituximab as well as trends for age in the first quartile ( Conclusion Patients developing SLE before age 28 with raised interferon scores may be forecast to develop severe disease, fail oral therapies, and require rituximab. While this retrospective analysis may be confounded by a survivorship bias, our findings are consistent with other literature on these variables as predictors of severe disease. Future work will analyse more biomarkers in a larger and more varied patient population. P163 Table 1:CharacteristicCYC/RTX=Yes n(%)CYC/RTX =No n(%)Univariable Hazard ratio (95% CI)Univariable p valueMultivariable Hazard Ratio (95% CI)Multivariable p valueAgeQ1: under 2822 (71%)9 (29%)2.25 (0.99,5.12)0.0541.74 (0.95,3.18)0.074Q2: 28-3812 (39%)19 (61%)1.03 (0.41,2.56)0.949Not includedNot includedQ3: 38-5212 (39%)19 (61%)1.52 (0.62,3.72)0.360Not includedNot includedQ4: over 528 (26%)23 (74%)referencereferenceNot includedNot includedEthnicityCaucasian42 (48%)46 (52%)1.17 (0.58,2.35)0.660Not includedNot includedAfroCaribbean, South Asian, East Asian, Other10 (36%)18 (64%)referencereferenceNot includedNot includedIFN Score A, mean (SD)–2.59 (–2.67)–3.84 (–2.71)1.10 (0.98,1.24)0.113Not includedNot includedIFN Score B, mean (SD)–2.61 (–1.16)–3.53 (–1.76)1.31 (1.05,1.64)0.0171.23 (0.98,1.55)0.079Anti-Sm/U1RNP Ab positive17 (61%)11 (39%)1.50 (0.84,2.67)0.171Not includedNot includedAnti-Ro(60) Ab positive14 (45%)17 (55%)0.88 (0.47,1.65)0.686Not includedNot included Disclosure S. Hassan: Grants/research support; S.U.H. is funded as NIHR Leeds Biomedical Research Centre Research Fellow. K. Mahmoud: None. L. Carter: None. K. Dutton: None. D. Li: None. I.N. Bruce: None. N. McHugh: None. T. Consortium: None. Z. Wigston: None. P. Emery: Consultancies; P.E. has received consultant fees from BMS, Abbott, Pfizer, MSD, Novartis, Roche and UCB. Grants/research support; P.E. has received research grants paid to his employer from Abbott, BMS, Pfizer, MSD and Roche. A. Psarras: None. M. Md Yusof: Grants/research support; M.Y.M.Y. is funded as a Wellcome fellow. E. Vital: Honoraria; E.M.V. has homoraria from Roche, GSK and AstraZenica. Grants/research support; E.M.V. has research grant support from Roche, GSK and AstraZenica.

Context ‘What does ‘The Public’ think?’ is a question often posed by researchers and policy makers, and public values are regularly invoked to justify policy decisions. Over time there has been a participatory turn in the social and health sciences, including health technology assessment and priority setting in health, towards citizen participation such that public policies reflect public values. It is one thing to agree that public values are important, however, and another to agree on how public values should be elicited, deliberated upon and integrated into decision-making. Surveys of public values rarely deliver unanimity, and preference heterogeneity, or plurality, is to be expected. Methods This paper examines the role of public values in health policy and how to elicit, analyse, and present values, in the face of plurality. We delineate the strengths and weaknesses of aggregative and deliberative methods before setting out a new empirical framework, drawing on Sunstein's Incompletely Theorised Agreements, based on three levels: principles, policies and patients. The framework is illustrated using a recognised policy dilemma – the provision of high cost, limited-effect medicines intended to extend life for people with terminal illnesses. Findings Application of the multi-level framework to public values permits transparent consideration of plurality, including analysis of coherence and consensus, in a way that offers routes to policy recommendations that are based on public values and justified in those terms. Conclusions Using the new framework and eliciting quantitative and qualitative data across levels of abstraction has the potential to inform policy recommendations grounded in public values, where values are plural. This is not to suggest that one solution will magically emerge, but rather that choices between policies can be explicitly justified in relation to the properties of public values, and a much clearer understanding of (in)consistencies and areas of consensus., Highlights • Public values are important for priority setting in health. • Public values are plural but we do not know how to account for plurality in policy. • Counting, coherence and consensus are relevant to resolving value plurality. • This paper presents a new empirical framework for analysis of public values. • The framework has potential to account for value plurality in health policy making.

The widening health gap between the best and worst-off in the UK requires innovative solutions that act upon the social, economic and environmental causes of ill-health. Initiatives such as microcredit have been conceptualised as having the potential to act on the social determinants of health. However, pathways that lead to this impact have yet to be empirically explored. People living on low incomes, who are financially-excluded, require access to credit to cope with everyday financial needs. While research shows the connections between debt and health, this link is often focused on over-indebtedness and negative health outcomes. In this paper, we investigate the impact of responsibly-delivered credit on the health and wellbeing of borrowers. In 2016-17, in-depth, semi-structured interviews were undertaken with fourteen borrowers from two microcredit providers offering personal and business microloans, operating in Glasgow, United Kingdom. Findings are presented, using social determinants of health as an analytic lens, and illustrated in a conceptual model explaining the loan mechanisms and pathways connecting microcredit to health and wellbeing. Microcredit, and the mechanisms through which it is delivered, were perceived by participants as positively impacting on their health and wellbeing. Access to flexible, responsibly-delivered, microloans enabled participants to plan and feel secure when faced with (un)expected financial events, reducing the associated stress, sustaining social relationships and empowering borrowers to take greater control over their lives. For some, receiving microcredit was stressful, as it is still a debt that needs to be repaid. Such stress can also be exacerbated by particular aspects of the lending model; for example, group lending. Our results contribute to growing evidence on the impact of financial inclusion approaches on health and wellbeing, highlighting the potential role of microcredit as a public health initiative and the need to support ‘alternative’ economic spaces in the UK to serve the financially-excluded.

Objectives To identify clinical factors associated with cancer risk in the idiopathic inflammatory myopathies (IIMs) and to systematically review the existing evidence related to cancer screening. Methods A systematic literature search was carried out on Medline, Embase and Scopus. Cancer risk within the IIM population (i.e. not compared with the general population) was expressed as risk ratios (RR) for binary variables and weighted mean differences (WMD) for continuous variables. Evidence relating to cancer screening practices in the IIMs were synthesized via narrative review. Results Sixty-nine studies were included in the meta-analysis. DM subtype (RR 2.21), older age (WMD 11.19), male sex (RR 1.53), dysphagia (RR 2.09), cutaneous ulceration (RR 2.73) and anti-transcriptional intermediary factor-1 gamma positivity (RR 4.66) were identified as being associated with significantly increased risk of cancer. PM (RR 0.49) and clinically amyopathic DM (RR 0.44) subtypes, Raynaud’s phenomenon (RR 0.61), interstitial lung disease (RR 0.49), very high serum creatine kinase (WMD −1189.96) or lactate dehydrogenase (WMD −336.52) levels, and anti-Jo1 (RR 0.45) or anti-EJ (RR 0.17) positivity were identified as being associated with significantly reduced risk of cancer. Nine studies relating to IIM-specific cancer screening were included. CT scanning of the thorax, abdomen and pelvis appeared to be effective in identifying underlying asymptomatic cancers. Conclusion Cancer risk factors should be evaluated in patients with IIM for risk stratification. Screening evidence is limited but CT scanning could be useful. Prospective studies and consensus guidelines are needed to establish cancer screening strategies in IIM patients.

Background Psoriasis is a chronic inflammatory disease of the skin affecting 2–3% of UK population. 30% of people affected by psoriasis will develop a distinct form of arthritis within 10 years of the skin condition onset. Although the pathogenesis of psoriatic arthritis is still unknown, there is a genetic predisposition triggered by environmental factors. Limited but convincing evidence link the gut microbiome to psoriatic arthritis. The Microbiome in Psoriatic ARThritis (Mi-PART) study propose is to characterise the microbiome-metabolic interface in patients affected by psoriatic arthritis to deepen our understanding of the pathogenesis of the disease. Methods This is a multicentre, prospective, observational study. Psoriatic arthritis (n = 65) and ankylosing spondylitis (n = 30) patients will be recruited in addition to a control group of healthy volunteers (n = 30). Patients eligibility will be evaluated against the Criteria for Psoriatic Arthritis (CASPAR), the Bath Ankylosing Spondylitis Activity Index (BASDAI) and the healthy volunteers who fulfil study inclusion and exclusion criteria. Information regarding their medical and medication history, demographics, diet and lifestyle will be collected. All the participants in the study will be asked to complete a 7-day food diary, to provide stool samples and to complete quality of life questionnaires. Routine clinical laboratory tests will be performed on blood and urine samples. Patients and healthy volunteers with gastrointestinal symptoms, previous history of cancer, gastrointestinal surgery in the previous 6 months or alcohol abuse will be excluded from the study. Discussion The aim of this trial is to characterise the microbiome of psoriatic arthritis patients and to compare it with microbiome of healthy volunteers and of patient with ankylosing spondylitis in order to define if different rheumatologic conditions are associated with characteristic microbiome profiles. Investigating the role of the microbiome in the development of psoriatic arthritis could deepen our understanding of the pathogenesis of the disease and potentially open the way to new therapies.

The aim of this guideline is to provide an update on evidence-based recommendations for treatment of adult patients with PsA. The previous BSR guidelines for PsA were published in 2012 and since that time, there have been many new advanced therapies licensed for PsA. This update will provide practical guidance for clinicians on the optimal selection of advanced therapies taking into account different domains of PsA (arthritis, enthesitis, dactylitis, axial disease and psoriasis) and key associated comorbidities. It will also update guidance on treatment strategy including the use of a treat-to-target approach. The guideline will be developed using the methods and processes outlined in Creating Clinical Guidelines: Our Protocol. (1) This development process to produce guidance, advice and recommendations for practice has National Institute for Health and Care Excellence (NICE) accreditation.

Objectives It has been over 10 years since the first report of autoantibodies directed against phenylalanyl tRNA synthetase (anti-Zo) in a patient with features of the anti-synthetase syndrome. In that time no further cases have been published. Here we aim to characterize more fully the clinical phenotype of anti-Zo–associated myositis by describing the clinical features of nine patients. Methods Anti-Zo was identified by protein-immunoprecipitation in patients referred for extended spectrum myositis autoantibody testing at our laboratory. Results were confirmed by immunodepletion using a reference serum. Medical records were retrospectively reviewed to provide detailed information of the associated clinical phenotype for all identified patients. Where possible, HLA genotype was imputed using Illumina protocols. Results Nine patients with anti-Zo were identified. The median age at disease onset was 51 years, and six patients were female. Seven patients had evidence of inflammatory muscle disease, seven of interstitial lung disease and six of arthritis. The reported pattern of interstitial lung disease varied with usual interstitial pneumonia, non-specific interstitial pneumonia and organizing pneumonia all described. Other features of the anti-synthetase syndrome such as RP and mechanics hands were common. HLA data was available for three patients, all of whom had at least one copy of the HLA 8.1 ancestral haplotype. Conclusion Patients with anti-Zo presenting with features of the anti-synthetase syndrome and interstitial lung disease is a common finding. Like other myositis autoantibodies, there is likely to be a genetic association with the HLA 8.1 ancestral haplotype.

Background Psoriatic nail disease is one of the six disease manifestations of psoriatic arthritis (PsA) in addition to peripheral arthritis, psoriasis, enthesitis, dactylitis and axial disease. Nail pitting is associated with an increased risk of developing PsA and onycholysis is associated with radiographic damage at the distal interphalangeal joints. Quantitative assessment of psoriatic nail disease is rarely performed in clinical practice therefore little is known about the burden of nail disease and effect of treatment in observational cohorts. We set out to quantify the burden of nail disease and response to b/tsDMARD treatment in a secondary care cohort. Methods Data were taken from the Bath PsA cohort. Patients fulfil CASPAR criteria and have clinical and patient reported outcomes at routine clinic follow-up visits. Patients commencing a b/tsDMARD with at least one follow up visit were included for analysis. Nail involvement was assessed using the Bath Nail score; pitting (0-10), onycholysis (0-10), hyperkeratosis (0-10) and severe deformity (0-10). Results 157 of 485 (32%) of the cohort commencing b/tsDMARDS had nail disease at baseline and were included in the analysis. At baseline nail pitting (65%) and onycholysis (57%) were the most frequent nail manifestations followed by hyperkeratosis (14%) and severe nail deformity (7%) (Table 1). At the first follow-up visit (mean duration 20 weeks), 39% of patients achieved clear nails. At the final follow-up visit (mean duration 59 weeks) 56% had clear nails and 44% of patients had residual nail disease with a median (IQR) nail score of 0 (0.0-2.0). Earliest improvements were seen in nail bed manifestations (onycholysis/ hyperkeratosis) whilst improvement in nail matrix features (pitting) occurred later (Table 1) (p < 0.001). Conclusion Psoriatic nail disease affects one third of those commencing b/tsDMARDs in this cohort. Earliest treatment responses are seen in features of psoriatic nail dystrophy that affect the nail distally. At 20 weeks 39% of those with nail disease at baseline achieve clear nails. At one year, 44% of patients have ongoing nail manifestations, but few patients have persistently high nail scores. Disclosures P. Nair None. A. Anthony None. C. Lovell None. E. Korendowych None. C. Cavill None. N. McHugh None. W. Tillett None.

Background Understanding the impact of psoriatic arthritis (PsA) on an individual and how the disease evolves over time is important when determining a therapeutic strategy. However, little is known about the natural course of arthritis, psoriasis, and enthesitis, their relative impact on quality of life and how disease burden in real world cohorts compares to clinical trial populations. We set out to describe the burden of disease and impact on quality of life in an observational UK secondary care cohort. Methods Cross sectional cohorts were selected from the Bath PsA cohort, group one with early disease (within 24 months of diagnosis), groups two and three with established disease (commencing therapy with first or second line biologic Disease Modifying Anti-Rheumatic Drug- bDMARD therapy respectively; assessments both at initiation and 3 months after initiation). Results Analyses were undertaken where sufficient data was available on 154 patients eligible for entry into the early PsA cohort (group 1), 240 patients eligible for the biologic initiator cohort (group 2) and 103 for the second line biologics initiator cohort. Cohort characteristics are reported in Table 1. The burden of joint disease was high in all cohorts and approximately comparable to clinical trial populations in group 2 commencing bDMARD (mean tender joints count 22 (SD 14), swollen 7 (SD 5) cDAPSA mean 36 (SD 15)). Mean Body Mass Index (BMI) rose from overweight in early disease to obese in established disease (table 1). There was little enthesitis in any group (LEI mean Conclusion We report high levels of residual joint disease, fatigue, obesity and work disability in both early and established PsA cohorts. Despite low absolute levels of residual skin and nail disease both become more strongly associated with worse quality of life in more established disease. Disclosures W. Tillett: Honoraria; Eli Lilly, Janssen, Novartis, Pfizer, UCB. Grants/research support; Abbvie, Eli Lilly, Celgene. A. Rambojun: Grants/research support; EPSRC. A. Bradley: Shareholder/stock ownership; Eli Lilly and Company Limited. Other; Employee of Eli Lilly and Company Limited. J. Mount: Shareholder/stock ownership; Eli Lilly and Company Limited. Other; Employee of Eli Lilly and Company Limited. C. Cavill: Grants/research support; Eli Lilly and Company Limited. E. Korendowych: Honoraria; Abbvie, Eli Lilly, Janssen, Novartis. Grants/research support; Eli Lilly and Company Limited. N. McHugh: Consultancies; Abbvie. Grants/research support; Eli Lilly and Company Limited.

Background: Psoriatic arthritis (PsA) is a progressive and often destructive joint disease affecting approximately 20% of people with psoriasis. Objectives: To investigate associations between obesity, changes in body mass index (BMI), alcohol intake and smoking status and the development of PsA in people with psoriasis. Methods: We undertook a cohort study involving incident cases of psoriasis identified from the U.K. Clinical Practice Research Datalink between 1998 and 2014. The associations between smoking, alcohol and BMI and development of PsA were assessed using generalized additive models. Additionally, the risks associated with a change in BMI during follow-up were investigated using distributed lag nonlinear models. Results: We identified 90 189 incident cases of psoriasis (42% male, mean age 51 years), of whom 1409 had a subsequent record of PsA diagnosis. BMIs of 25·0–29·9, 30·0–34·9 and ≥ 35·0 kg m −2 were significantly associated with an increased risk of developing PsA compared with BMIs < 25·0 kg m −2: adjusted odds ratios (95% confidence intervals) 1·79 (1·46–2·19), 2·10 (1·67–2·63) and 2·68 (2·09–3·43), respectively. Reducing BMI over a 10-year period (linearly) was associated with a reduction in the risk of developing PsA compared with BMI remaining constant over the same period. Increased risks of developing PsA were associated with moderate drinking but not with former or heavy drinking or with current or past smoking status. Conclusions: In this incident psoriasis cohort, increased BMI and moderate drinking, but not heavy drinking or smoking status, were associated with an increased risk of PsA in people with psoriasis. Importantly, we have shown that reducing weight may result in a reduction in the risk of developing PsA. What's already known about this topic?. There is some evidence that increased body mass index is associated with an increased risk of developing psoriatic arthritis. There are conflicting results surrounding the relationship between smoking and the development of psoriatic arthritis among patients with psoriasis. What does this study add?. Using a nonlinear and lagged effect of body mass index measured over time we have shown that reducing body mass index may be associated with a reduction in the risk of developing psoriatic arthritis. We have found no evidence that smoking alters the risk of developing psoriatic arthritis in patients with psoriasis.

Social Impact Bonds (SIBs) are an innovation wherein, in theory, private investment, instead of government funding, is levered to fund social interventions (Warner, 2013; Edmiston & Nicholls 2018)....

Objective:To evaluate and update the evidence for the measurement properties of the Psoriatic Arthritis Impact of Disease (PsAID12) questionnaire to measure health-related quality of life (HRQoL) in psoriatic arthritis (PsA).Methods:The PsAID12 psychometric evidence was gathered in a systematic literature review in PsA (registration number: CRD42016032546). The study quality was appraised using the Consensus-based Standards for the selection of health Measurement Instruments–Outcome Measures in Rheumatology (COSMIN-OMERACT) good methods check-list. Content validity, test–retest reliability, construct validity, longitudinal construct validity, discrimination, and thresholds of meaning were appraised. Additional analyses for construct validity, responsiveness, and sensitivity to change were conducted in available observational data sets after prespecified hypotheses were formulated.Results:Eight publications (129-474 patients) were analyzed. The PsAID12 fulfilled OMERACT criteria for content validity (patients and physicians endorsed content match with PsA HRQoL domain), feasibility (endorsed by patients and physicians), and test–retest reliability (intraclass correlation coefficient: 0.91-0.95). A priori construct validity hypotheses were mostly met: Psoriatic Arthritis Impact of Disease had high correlation with generic ( r = 0.76-0.87) and PsA-specific HRQol measures (0.8), and with measures of physical function (0.66-0.72), work productivity (0.69-0.75), pain (0.83), and fatigue (0.84). Psoriatic Arthritis Impact of Disease had moderate-high correlation with measures of patient global (0.49-0.84) and dermatologic HRQoL (0.36-0.53). Correlations were higher with generic HRQoL measured by short form-36 physical component score (0.47-0.73) versus short form-36 mental component score (0.22-0.60). Three studies confirmed known group validity of PsAID12 according to PsA disease activity. Psoriatic Arthritis Impact of Disease discriminated between change groups in 2 longitudinal studies (standardized response mean: 0.74-0.91, 53 and 105 patients). The minimal clinically important improvement was 3 and 1.4 points.Conclusion:Psoriatic Arthritis Impact of Disease had evidence for good content and construct validity, reliability, and longitudinal construct validity and is ready to evaluate in clinical trials.

Myositis autoantibodies can help subset patients into more homologous groups, aiding in diagnosis and helping to predict potential disease complications. In recent years, a number of novel myositis autoantibodies including anti-HMGCR, anti-SAE, anti-CN1A and anti-PUF60 have been identified and characterised, with the majority of myositis patients now having a detectable autoantibody. Preliminary studies have also led to the discovery of a number of emerging myositis autoantibodies including anti-SMN, anti-cortactin, anti-NPC and anti-FHL1, which when fully characterised may provide additional insight into disease pathogenesis as well as providing additional subsets in the serological classification of myositis. This chapter describes the prevalence and clinical associations of these new and emerging biomarkers.

The discovery of an increased repertoire of autoantibodies associated with idiopathic inflammatory myositis has important implications for enabling earlier diagnosis. Either a myositis-specific or a myositis-associated autoantibody is present in about 70% of adult and juvenile cases and in many cases identify specific patterns of disease and co-morbidities. In the future, it is likely that knowledge of a myositis autoantibody profile will be more fully incorporated into diagnostic and classification criteria and lessen the need for more invasive investigative procedures. In the meantime, there is a need for standardisation of commercial assays that are becoming more available, awareness of the reliability of initial autoantibody screening procedures, and guidance on how to interpret myositis autoantibody results in a given clinical context.

OBJECTIVES: Raynaud's phenomenon (RP) is the commonest manifestation of systemic sclerosis (SSc). RP is an episodic phenomenon, not easily assessed in the clinic, leading to reliance on self-report. A thorough understanding of the patient experience of SSc-RP is essential to ensuring patient-reported outcome (PRO) instruments capture domains important to the target patient population. We report the findings of an international qualitative research study investigating the patient experience of SSc-RP.METHODS: Focus groups (FGs) of SSc patients were conducted across 3 scleroderma centers in the US and UK, using a topic guide and a priori purposive sampling framework devised by qualitative researchers, SSc patients and SSc experts. FGs were audio recorded, transcribed, anonymised and analysed using inductive thematic analysis. FGs were conducted until thematic saturation was achieved.RESULTS: Forty SSc patients participated in 6 focus groups conducted in Bath (UK), New Orleans (US) and Pittsburgh (US). Seven major themes were identified that encapsulate the patient experience of SSc-RP: physical symptoms, emotional impact, triggers & exacerbating factors, constant vigilance & self-management, impact on daily life, uncertainty and adaptation. The inter-relationship of the 7 constituent themes can be arranged within a conceptual map of SSc-RP.CONCLUSION: We have explored the patient experience of SSc-RP in a diverse and representative SSc cohort and identified a complex interplay of experiences that result in significant impact. Work to develop a novel PRO instrument for assessing the severity and impact of SSc-RP, comprising domains/items grounded in the patient experiences of SSc-RP identified in this study is underway. This article is protected by copyright. All rights reserved.

Background The close temporal association between onset of some connective tissue diseases and cancer suggests a paraneoplastic association. Adult patients with scleroderma with anti-RNA polymerase III autoantibodies and adult patients with dermatomyositis with anti-transcriptional intermediary factor 1 (anti-TIF1) or anti-nuclear matrix protein 2 (anti-NXP2) autoantibodies have a significantly increased risk of developing cancer. Autoantibodies may serve as biomarkers for early detection of cancer and also could be relevant for prediction of responses to immune therapies. We aimed to test whether myositis and scleroderma specific or associated autoantibodies are detectable in individuals with lung cancer. Methods Serum from 60 Caucasian patients with lung cancer (30 with small cell lung cancer, 30 with non-small cell lung cancer) was screened for myositis and scleroderma specific and associated autoantibodies by radiolabelled immunoprecipitation. Results Anti-TIF1, anti-NXP2 or anti-RNA polymerase III autoantibodies were not detected in any of the 60 patients with lung cancer. Anti-glycyl-transfer RNA (tRNA) synthetase (anti-EJ) autoantibodies were detected in one patient with non-small cell lung cancer. No other known myositis or scleroderma autoantibodies were identified. Conclusions Myositis and scleroderma specific autoantibodies, including anti-TIF1, anti-NXP2 and anti-RNA polymerase III, are rare in patients with lung cancer without an autoimmune disease. We report here the first case of anti-EJ autoantibodies being detected in a patient with lung cancer without clinical or radiographic evidence of the anti-synthetase syndrome. Electronic supplementary material The online version of this article (10.1186/s13075-018-1678-9) contains supplementary material, which is available to authorized users.

Objective To identify different trajectories of disease activity in patients with RA following initiation of a first anti-TNF. Methods Patients with RA starting their first anti-TNF between 2001 and 2013 were selected from the British Society for Rheumatology Biologics Register for RA. Six-monthly DAS28-ESR scores were used to identify trajectories of disease activity using latent class modelling. Data were included for six follow-ups after registration (approximately 3 years). Subgroup analysis examined changes in disease activity profiles over time. Results A total of 14 436 patients with RA starting their first anti-TNF were enrolled between 2001 and 2013 (13 115 between 2001 and 2008, 1321 between 2010 and 2013). The mean number of DAS28-ESR scores was 3.5/patient (s.d. 2.1), with a mean of 184.9 days (s.d. 69.9) between scores. The DAS28-ESR nadir was achieved within 250 days of commencing anti-TNF, although apparent trajectory divergence emerged by first 6-monthly follow-up at 180 days. Four distinct response trajectories comprised the most stable model. Most patients fitted into ‘modest’ (7986 patients; 55.3%) or ‘substantial’ (4676 patients; 32.4%) response trajectories. Of the remainder, 1254 (8.7%) and 520 (3.6%) fitted ‘maximal’ and ‘minimal’ response trajectories, respectively. There was a significant (P < 0.01) increase in proportion achieving ‘maximal’ response between 2001–2008 and 2010–2013. Conclusion This is the largest study to identify long-term response trajectories with anti-TNF. By 6 months, longer-term trajectory profiles of DAS28 could already be identified, with many patients identified earlier. The majority of patients had persistent moderate response, equivalent to maintained DAS28-ESR moderate disease activity. The maximal response trajectory (equivalent to sustained DAS2-ESR remission) was only achieved by approximately one-third of patients.

In this small case series, all eight patients were women in their fifth and sixth decades. This is similar to the female predominance in morphoea and less in keeping with eosinophilic fasciitis (EF). All cases had diffuse induration of their limbs with both proximal and distal patterns of distribution, and five of the patients exhibited peau d'orange skin. All patients had diffuse induration of the lower limbs and half had restricted ankle movements. Six patients had concomitant superficial morphoea. This group of patients demonstrated a unique subtype of the morphoea spectrum with some features overlapping with EF. However, there appear to be points of distinction, and we propose that some previously reported cases labelled as EF would be better described as having morphoea profunda (MP). Methotrexate may be a useful treatment for MP, hence it is important to distinguish this from EF, as management may differ.

Objectives: Autoantibodies targeting ubiquitously expressed nuclear antigens can be identified in most patients with SSc. Cytoplasmic autoantibodies (in otherwise ANA-negative sera) targeting eukaryotic initiation factor-2B (anti-eIF2B) have recently been identified in SSc with clinical associations to dcSSc disease and interstitial lung disease (ILD), although the majority of samples originated from a tertiary SSc-ILD centre. We investigated the prevalence and clinical associations of recently described SSc-specific (including anti-eIF2B) and other cytoplasmic autoantibodies in ANA-negative sera obtained from a large representative SSc cohort.Methods: ANA-negative sera from the Scleroderma Family Registry and DNA Repository underwent indirect immunofluorescence, radiolabelled protein immunoprecipitation (± immunodepletion) to identify anti-eIF2B and other CTD-related autoantibodies. The clinical phenotype of positive samples was evaluated.Results: Immunoprecipitation was performed on 128 ANA-negative samples (obtained from 3249 SSc patients). Anti-eIF2B antibodies were present in nine patients (7%), the majority of whom had dcSSc (8/9). SSc-ILD was present in all anti-eIF2B patients for whom chest imaging was available (7/9). Anti-synthetase autoantibodies (targeting PL12, PL7, OJ and Zo) were identified in seven patients (5.5%), all of whom fulfilled the 2013 ACR/EULAR classification criteria for SSc and had evidence of SSc-ILD where relevant outcomes were available for evaluation. Anti-RuvBL1/2 antibodies were identified in two patients with SSc-overlap syndromes.Conclusion: Anti-eIF2B antibodies are cytoplasmic SSc-specific autoantibodies with strong clinical associations with dcSSc and SSc-ILD found in ANA-negative sera. Anti-synthetase autoantibodies, and other recently discovered SSc-specific antibodies such as anti-RuvBL1/2, can also be identified in ANA-negative SSc.

Background:Biologic interventions using highly specific immuno-modulatory biologic disease-modifying anti-rheumatic drugs (bDMARDs) represent a rapidly developing therapeutic approach to the treatment of Psoriatic Arthritis (PsA). However, despite high rates of response, adverse events, primary and secondary inefficacy are common, and multiple sequential lines of bDMARDs are often required. Data on drug persistence, as a surrogate for response, from national registries indicates switching has become accepted routine practice. One third of patients will fail or discontinue their first biologic with a significant proportion switching on to a 3rd biologic or higher.1-4 Due to a lack of evidence on the response to sequential therapies, individual patients may not have further lines routinely funded after three bDMARDs in the UK. While limiting lines of therapy remains a UK concern, many countries with rationed healthcare systems follow the UK model of drug usage.Objectives:To describe the response to sequential lines of bDMARD therapy prescribed in routine care in a UK single centre cohort.Methods:A retrospective sample of patients with PsA who fulfilled CASPAR criteria and had received at least one bDMARD were taken from the Bath longitudinal cohort for inclusion in the study. Clinical and laboratory variables that constitute physician and patient-reported outcome measures were collected at baseline and after a median (range) follow-up of 3 months (2-5) into their respective therapy line in accordance with the National Institute for Health and Care Excellence (NICE) rules. The mean change with a 95% confidence interval (CI) was used to report the difference between the baseline and follow-up measures. All patients provided consent to use their data collected during routine care, and ethical approval by the local committee was granted.Results:The patients mean age was 57.7 (SD 12.2) with a median (range) disease duration of 14.4 years (9.7 – 23.2). Data was available for 194 patients commencing 1st line bDMARD, 106 (2nd line), 93 (3rd line), 33 (4th line), 12 (5th line), and 9 (6th line and higher) from a total of 759 patients in the cohort. Mean tender and swollen joint count at baseline 1st bDMARD was 7 (SD 4.7) and 22 (SD 14.0), pain visual analogue scale 50 (SD 27.6) and PASI 1.3 (SD 2.2). Reasons for changing biological therapies include lack or loss of efficacy, intolerance, side effects, and comorbidities. Mean levels of joint disease at drug initiation did not diminish with subsequent lines of therapy. Clinical and patient reported outcomes by line of therapy are reported in Figure 1. Clinical responses were greatest to first line bDMARD, however clinically relevant DAPSA improvements were seen up to 5th line. Absolute levels of psoriasis in the cohort were low, however improvement in PASI was achieved across all lines of therapy. Patient and Physician Global Assessments (1-5 on Likert scale) and the Pain Visual analogue score (VAS on 1-10 Likert scale) showed a similar trend with greatest improvement to first line treatment across all lines of therapy.Conclusion:In this study we report the clinical response to sequential lines of bDMARD therapy for active PsA in routine clinical practice. Clinical response was greatest to the first line bDMARD but overall improvement in DAPSA, PASI or pain response did not appear to diminish up to 5th line. Further study in larger cohorts is required to confirm this finding and build on our understanding of clinical response to sequential lines of bDMARD therapy.References:[1]Hyrish et al 2006 Rheum 45, 1558-65[2]Kawabe A. 2020 Arth Res Ther 22, 136[3]Park DJ. 2017 Clin Rheum 36, 1013-22[4]Karlsson. 2007 JA Rheum 47,507-13Figure 1.Clinical and patient reported outcomes by line of therapyDisclosure of Interests:Abuelmagd Abdalla: None declared, Adwaye Rambojun: None declared, Laura C Coates Speakers bureau: AbbVie, Amgen, Biogen, Celgene, Gilead, Eli Lilly, Janssen, Medac, Novartis, Pfizer, and UCB., Consultant of: AbbVie, Amgen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Eli Lilly, Gilead, Janssen, Novartis, Pfizer, and UCB, Grant/research support from: AbbVie, Amgen, Celgene, Eli Lilly, Pfizer, and Novartis, Eleanor Korendowych Consultant of: Abbvie, Celgene, Janssen, Lilly and Novartis., Neil McHugh: None declared, William Tillett Speakers bureau: AbbVie, Amgen, Celgene, Lilly, Janssen, Novartis, Pfizer Inc., and UCB, Consultant of: AbbVie, Amgen, Celgene, Lilly, Janssen, Novartis, MSD, Pfizer Inc., and UCB., Grant/research support from: AbbVie, Celgene, Eli Lilly, Janssen, Novartis, Pfizer Inc., and UCB.

Background:Psoriatic arthritis (PsA) is an inflammatory arthritis characterised by pain, swelling and stiffness in the joints and affects approximately 0.3 to 1.02% of the UK population [1]. PsA may result in limited physical function and reduced quality of life [2] and is associated with work disability and unemployment [3]. Patients who have the inflammatory skin condition, psoriasis, are at greater risk of developing PsA than those without.Objectives:There is no definitive test for PsA. It is usually diagnosed by rheumatologists in secondary care, after referral from primary care. Evidence suggests a delay in diagnosis results in worse outcomes for patients. This study is nested within a randomised controlled trial (RCT) of a new clinical care pathway. The RCT is testing whether screening primary care patients with psoriasis for symptoms of PsA leads to earlier diagnosis and improved outcomes, compared to usual care. This qualitative study explored the acceptability and impact of screening.Methods:Telephone interviews were conducted with patients with psoriasis from two secondary UK care centres taking part in the RCT. The semi-structured interviews explored patients’ thoughts and feelings around screening, the impact of the screening outcome and any changes they made as a result. The semi-structured format allowed flexibility to ask questions that probed more deeply and develop new lines of enquiry based on patients’ responses. Patients who did and did not receive a diagnosis of PsA were interviewed.Results:Twenty-four patients participated in the study (15 women / 9 men) ranging in age from 35 to 73 years old. The length of time patients had psoriasis ranged from 6 to 60 years. Eleven patients were diagnosed with PsA. A Framework Analysis Approach was used to analyse the data. This allowed for an exploration of the predefined areas (the screening process) as well as remaining open to capturing other related experiences and views of patients. Four main themes represent the data (Table 1).Table 1.Main themeSub-themes1. Living with psoriasis and psoriatic arthritis:1. Understanding of psoriasis – causes, symptoms, treatments‘It’s [psoriasis] socially debilitating…makes you look a real mess’2. Effects of psoriasis on self, personal and working life‘It’s almost as if the world’s on your shoulders’3. Awareness of PsA2. Experience of screening:1. Thoughts and feelings prior to screening‘I was able to talk and be listened to’2. Valuing ‘high quality’ care‘It’s a lightbulb moment…explained why things were a bit stiff and achy’3. Impact of screening outcome3. Gaining control:1. Increased awareness and knowledge of psoriasis and PsA‘element of surprise that this arthritis should be connected to it [psoriasis]’2. Improved self-management‘You’ve got to learn to listen to your body’3. Early diagnosis of PsA4. Future screening programs:1. Changes to questionnaires‘there weren’t really any questions about were you in pain’2. Use of case studies, sign-posting‘support groups…peer support is crucial with long-term conditions’3. Removing barriers to screeningConclusion:This study indicates screening was viewed as a positive and reassuring experience. Patients valued the fact that screening appointments were not rushed and felt they were being listened to. Patients valued learning about psoriasis and PsA and referred to making changes beneficial to their health. Screening enabled patients to get the help they needed if diagnosed, provided relief if not diagnosed, and sometimes led to the diagnosis of a different condition.References:[1]Gladman DD, Antoni C, Mease P, Clegg DO, Nash P. Psoriatic arthritis: epidemiology, clinical features, course, and outcome. Ann Rheum Dis 2005;64(Suppl 2):ii14–7[2]Tillett W, de-Vries C, McHugh NJ. Work disability in psoriatic arthritis: a systematic review. Rheumatology 2012;51:275–83.[3]Alinaghi F, Calov M, Kristensen LE et al. Prevalence of psoriatic arthritis in patients with psoriasis: a systematic review and meta-analysis of observational and clinical studies. J Am Acad Dermatol 2019;80:251–65.e19Acknowledgements:On behalf of the PROMPT study team.Disclosure of Interests:None declared

Background:Low disease activity state has been defined using SLEDAI and used as treatment target in SLE. However, there has not been any such definition using BILAG-2004 index (BILAG-2004).Objectives:This study was to determine if low disease activity state according to BILAG-2004 is valid for use as treatment target in SLE. We also assessed disease activity longitudinally using BILAG-2004 systems tally (BST). BST is an alternative way of representing BILAG-2004 scores that combines the flexibility and simplification of numerical scoring of BILAG-2004 with the clinical intuitiveness of BILAG-2004 structure.Methods:This was a prospective multi-centre longitudinal study in the UK of an inception cohort of SLE patients (recruited within 12 months of achieving 1997 ACR revised criteria for SLE). Data were collected on disease activity (BILAG-2004 and BILAG2004-Pregnancy Index during pregnancy), SLICC/ACR DI (SDI), cumulative drug exposure and death at every visit. This study ran from 1st January 2005 to 31st December 2017. Four low disease activity states (LDA) were defined using BILAG-2004: 1) BILAG-2004 LDA when all 9 systems had scores of C, D or E on assessment (no Grade A or B), 2) BST LDA when there was persistent score of C, D or E in all 9 systems between 2 consecutive visits (equivalent to 2 consecutive visits with BILAG-2004 LDA), 3) BILAG-2004 Remission when all 9 systems had scores of D or E on assessment and 4) Persistent Remission when there was persistent score of D or E in all 9 systems between 2 consecutive visits. Longitudinal analysis using Poisson regression with random effects model was used with development of new damage as the outcome of interest. Gender, cardiovascular risk factors, antiphospholipid syndrome status and most drugs (except hydroxychloroquine, glucocorticoids, mycophenolate and cyclophosphamide) were excluded from the model as they were not associated with development of damage in univariate analysis.Results:273 patients were recruited (91.2% female, 59.3% Caucasian, 17.2% African/Caribbean, 17.2% South Asian) with mean age at recruitment of 38.5 years (SD 14.8). 97.8% had no damage at recruitment (2.2% had SDI score of 1). Median follow-up was 73.4 months (range: 1.8, 153.8) with total follow-up of 1767 patient-years. There were 13 deaths and 114 new damage items occurred during follow-up. There were 6674 assessments with disease activity score: 319 assessments with Grade A activity in 95 patients (84.6% had only 1 system with grade A, range: 1 - 4) and 1704 assessments with Grade A or B activity in 239 patients (78.7% had only 1 system with Grade A or B, range: 1 - 5).BILAG-2004 LDA was achieved in 74.5% of assessments (from 271 patients). BILAG-2004 Remission occurred in 28.2% of assessments (from 234 patients).6401 observations with BST were available (1 observation derived from change in activity between 2 consecutive assessments) and 63.7% were in BST LDA. There was no observation with Persistent Remission between consecutive visits.Table 1 summarises multivariate analysis which showed BILAG-2004 LDA to be inversely associated with damage. Similar results were obtained with BILAG-2004 Remission (RR 0.60 with 95% CI 0.38, 0.96) and BST LDA (RR 0.65 with 95% CI 0.43, 0.99). Cumulative drug exposure since recruitment for mycophenolate was protective against new damage (RR 0.99 with 95% CI 0.99, 0.99).Table 1.VariableRelative Risk (95% CI) for New DamageEthnicityAfro-Caribbean1.22 (0.68, 2.18)South Asian1.81 (0.97, 3.38)Others2.22 (0.63, 7.85)Age at diagnosis1.06 (1.04, 1.08)Prior SDI score0.68 (0.43, 1.06)BILAG-2004 LDA0.60 (0.39, 0.94)Hydroxychloroquine since last visit (per g)0.99 (0.98, 0.99)Steroids since last visit (per 100mg)1.02 (1.01, 1.03)Cyclophosphamide since last visit (per g)1.67 (1.15, 2.41)Conclusion:BILAG-2004 LDA and BST LDA are valid treatment targets in SLE. BILAG-2004 Remission and Persistent Remission are uncommon, which make them unrealistic as a treatment target.References:[1]Yee C. S., et al. The BILAG-2004 systems tally – a novel way of representing the BILAG-2004 index scores longitudinally. Rheumatology (Oxford) 2012; 51[11]: 2099-2105.Acknowledgements :Versus Arthritis, Vifor PharmaDisclosure of Interests:Chee-Seng Yee Consultant of: Bristol Myers Squibb, ImmuPharma, Grant/research support from: Vifor Pharma, Caroline Gordon Speakers bureau: UCB, Consultant of: Center for Disease Control, Astra-Zeneca, MGP, Sanofi and UCB, Mohammed Akil: None declared, Peter Lanyon: None declared, Christopher John Edwards Consultant of: Glaxo Smith Kline, Roche, Grant/research support from: Glaxo Smith Kline, Roche, David Isenberg: None declared, Anisur Rahman: None declared, Lee-Suan Teh: None declared, Sofia Tosounidou: None declared, Robert Stevens: None declared, Ahtiveer Prabu: None declared, Bridget Griffiths: None declared, Neil McHugh: None declared, Ian N. Bruce: None declared, Yasmeen Ahmad: None declared, Munther Khamashta: None declared, Vernon Farewell: None declared

Background:BILAG-2004 Index (BILAG-2004) has undergone construct and criterion validity and is used to assess disease activity in SLE. However, its predictive validity has yet to be established.Objectives:This study was to determine if disease activity according to BILAG-2004 was predictive of development of damage in an inception cohort.Methods:This was a prospective multi-centre longitudinal study in the UK of an inception cohort of SLE patients (recruited within 12 months of achieving 1997 ACR revised criteria for SLE). Data were collected on disease activity (BILAG-2004 and BILAG2004-Pregnancy Index during pregnancy), SLICC/ACR DI (SDI), cumulative drug exposure and death at every visit. Information on cardiovascular risk factors (hypertension, diabetes mellitus, hypercholesterolaemia and smoking status) and antiphospholipid syndrome status were also collected. This study ran from 1st January 2005 to 31st December 2017. Longitudinal analysis using Poisson regression with random effects model was used to determine predictors of development of new damage. Death was not included in the analysis due to small numbers.Results:273 patients were recruited (91.2% female, 59.3% Caucasian, 17.2% African/Caribbean, 17.2% South Asian) with mean age at recruitment of 38.5 years (SD 14.8). 97.8% had no damage at recruitment (2.2% had SDI score of 1). Median follow-up was 73.4 months (range: 1.8, 153.8) with total follow-up of 1767 patient-years. Prevalence of risk factors during follow-up were: hypertension 23.1%, hypercholesterolaemia 35.5%, diabetes mellitus 5.5%, smoker or ex-smoker 44% and antiphospholipid syndrome 7%. There were 13 deaths and 114 new damage items occurred during follow-up.There were 6674 assessments with disease activity score: 293 assessments with Grade A activity in 95 patients (92.4% had only 1 system with grade A, range: 1 - 4) and 1704 assessments with Grade A or B activity in 239 patients (78.7% had only 1 system with Grade A or B, range: 1 - 5).Univariate analysis showed that gender, cardiovascular risk factors, antiphospholipid syndrome and most drug exposure (except hydroxychloroquine, glucocorticoids, mycophenolate and cyclophosphamide) were not associated with new damage (they were not included in the multivariate analysis).Table 1 summarises multivariate analysis. Similar results were obtained when the disease activity variable was changed to Number of Systems with Grade A per assessment (RR 2.04 with 95% CI: 1.05, 3.94). Analysis using BILAG-2004 systems tally showed that persistent minimal disease was protective of development of damage (RR 0.74 with 95% CI: 0.57, 0.95). Cumulative drug exposure since recruitment for mycophenolate was protective against new damage (RR 0.99 with 95% CI 0.99, 0.99) but not cumulative drug exposure since last visit.VariableRisk Ratio (95% CI) for New DamageEthnicity Afro-Caribbean1.21 (0.68, 2.17) South Asian1.81 (0.97, 3.36) Others2.37 (0.68, 8.20)Age at diagnosis1.06 (1.04, 1.08)Prior SDI score0.69 (0.44, 1.08)Constitutional A or Bunreliable estimate due to low numbersMucocutaneous A or B1.80 (1.04, 3.14)Neuropsychiatric A or B4.68 (1.68, 13.05)Musculoskeletal A or B0.76 (0.33, 1.73)Cardiorespiratory A or B0.35 (0.05, 2.59)GIT A or Bunreliable estimate due to low numbersOphthalmic A or Bunreliable estimate due to low numbersRenal A or B2.08 (0.99, 4.40)Haematological A or B4.37 (1.15, 16.65)Hydroxychloroquine since last visit (per g)0.99 (0.98, 0.99)Prednisolone since last visit (per 100mg)1.01 (1.00, 1.02)Cyclophosphamide since last visit (per g)1.42 (0.94, 2.14)Conclusion:Active disease (Grade A or B) according to BILAG-2004 index is predictive of development of new damage in SLE patients.References:[1]Yee C. S., et al. The BILAG-2004 systems tally – a novel way of representing the BILAG-2004 index scores longitudinally. Rheumatology (Oxford) 2012; 51[11]: 2099-2105.Acknowledgements:Versus Arthritis and Vifor PharmaDisclosure of Interests:Chee-Seng Yee Consultant of: Bristol Myers Squibb, ImmuPharma, Grant/research support from: Vifor Pharma, Vernon Farewell: None declared, Mohammed Akil: None declared, Peter Lanyon: None declared, Christopher John Edwards Consultant of: Glaxo Smith Kline, Roche, Grant/research support from: Glaxo Smith Kline, Roche, David Isenberg: None declared, Anisur Rahman: None declared, Lee-Suan Teh: None declared, Sofia Tosounidou: None declared, Robert Stevens: None declared, Ahtiveer Prabu: None declared, Bridget Griffiths: None declared, Neil McHugh: None declared, Ian N. Bruce: None declared, Yasmeen Ahmad: None declared, Munther Khamashta: None declared, Caroline Gordon Speakers bureau: UCB, Consultant of: Center for Disease Control, Astra-Zeneca, MGP, Sanofi and UCB

Background:There is a recognised need for a continuous composite measure of disease activity for the assessment of Psoriatic Arthritis (PsA) in routine clinical settings to allow objective assessment of response and implementation of treat to target.1 Longer multidimensional measures are considered less feasible in routine care and a number of shorter measures have been proposed including, the Disease Activity Score for Psoriatic Arthritis (DAPSA), Disease Activity Score 28 (DAS28), the 3 Visual Analogue Scale (VAS) (comprising physician global VAS, patient global VAS and patient skin VAS) or 4 VAS (comprising physician global VAS, patient pain VAS, joint VAS and patient skin VAS). Testing of these measures in clinical trial datasets has been suggested but thresholds of meaning have not been established.2Objectives:To estimate clinically relevant thresholds of disease activity and improvement for composite measures for routine clinical practice in PsA.Methods:Clinical and patient reported outcome measures were assessed in patients fulfilling CASPAR criteria for PsA at three consecutive follow up visits in a UK multicentre observational study. Participants underwent clinical assessment and completed patient reported measures including health anchor questions. Estimates for Minimal Detectible Change (MDC) were derived using 1.96*2*Standard Error of the Mean (SEM). Minimal Clinically Important Difference (MCID) for improvement were derived using the health anchor method and two distribution methods (Table 1). Thresholds for low, moderate and high disease activity were triangulated from established cut-off values for the patient global VAS, PASDAS and DAPSA.Table 1.Minimal Clinically Important Difference (MCID) and Minimal detectable change (MDC)ANCHOR (MEDIAN)DISTRIBUTION#1DISTRIBUTION #2MDCCPDAI0.51.491.54.16GRACE0.260.60.772.18PASDAS1.220.640.761.58DAS280.20.850.621.463VAS1.131.160.913.124VAS1.110.960.942.45DAPSA7.259.0910.4035.63Disease Activity Score for Psoriatic Arthritis (DAPSA); Psoriatic Arthritis Disease Activity Score (PASDAS); Composite Psoriatic Arthritis Disease Activity Index (CPDAI); Disease Activity Score 28 (DAS28).Distribution #1: Baseline standard deviation (sd) * √ 1 – Cronbach’s alphaDistribution #2: 0.5 * baseline sdMinimal detectable change (MDC): 1.96*2*SEM where SEM = baseline sd √1 - ICCResults:139 subjects were recruited (59 male, 80 female, mean (range) age (years) 52.7 (19 – 83), mean (range) duration of psoriasis (years) 21.9 (2 – 71), mean (range) duration of psoriatic arthritis (years) 6.1 (0 – 41). Cut-off values for low, moderate and high disease activity were 1.3, 2.4, and 4.8 for the 3 Vas and 1.6, 2.8 and 5.0 for the 4 VAS (Figure 1). Estimates for the MCID and MDC for the continuous composite measures and are reported in Table 1.Conclusion:We report estimates of clinically relevant improvements for continuous composite measures in PsA and estimates of low, moderate and high disease activity for the 3 and 4 VAS scales. The thresholds of meaning can now be tested in independent observational and clinical trial datasets.References:[1]Coates et al 2018 A&R Mar;70(3):345-355.[2]Tillett W et al 2021 J Rheum In PressAcknowledgements Funding:This report is independent research funded by the National Institute for Health Research, Programme Grants for Applied Research [Early detection to improve outcome in patients with undiagnosed PsA (‘PROMPT’), RP-PG-1212-20007]. The views expressed are those of the authors and not necessarily those of the NIHR or the Department of Health and Social Care.Disclosure of Interests:William Tillett Speakers bureau: AbbVie, Amgen, Celgene, Lilly, Janssen, Novartis, MSD, Pfizer, and UCB, Consultant of: AbbVie, BMS, Celgene, Lilly, Janssen, Novartis, Pfizer, and UCB, Grant/research support from: AbbVie, BMS, Janssen, Novartis, Pfizer, and UCB., Julia Day: None declared, Neil McHugh: None declared, Oliver FitzGerald Speakers bureau: AbbVie, BMS, Celgene, Lilly, Janssen, Novartis, Pfizer, and UCB, Consultant of: AbbVie, BMS, Celgene, Lilly, Janssen, Novartis, Pfizer, and UCB, Grant/research support from: AbbVie, BMS, Janssen, Novartis, Pfizer, and UCB., Laura C Coates Speakers bureau: AbbVie, Amgen, Biogen, Celgene, Gilead, Eli Lilly, Janssen, Medac, Novartis, Pfizer, and UCB., Consultant of: AbbVie, Amgen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Eli Lilly, Gilead, Janssen, Novartis, Pfizer, and UCB, Grant/research support from: AbbVie, Amgen, Celgene, Eli Lilly, Pfizer, and Novartis, Philip Helliwell: None declared

BACKGROUND: A recent systematic review identified four candidate serum-soluble bone-turnover biomarkers (dickkopf-1, Dkk-1; macrophage-colony stimulating factor, M-CSF; matrix metalloproteinase-3, MMP-3; osteoprotegerin, OPG) showing possible association with psoriatic arthritis (PsA). We aimed to: (i) confirm and determine if these four biomarkers are associated with PsA; (ii) differentiate psoriasis cases with and without arthritis; and (iii) differentiate PsA cases with and without axial arthritis.METHODS: A prospective cross-sectional comparative two-centre study recruited 200 patients with psoriasis without arthritis (PsC), 127 with PsA without axial arthritis (pPsA), 117 with PsA with axial arthritis (psoriatic spondyloarthritis, PsSpA), 157 with ankylosing spondylitis (AS) without psoriasis, and 50 matched healthy controls (HC). Serum biomarker concentrations were measured using ELISA. Multivariable regression and receiver operating characteristic analyses were performed.RESULTS: MMP-3 concentrations were significantly higher and M-CSF significantly lower in each arthritis disease group compared with HC (p ≤ 0.02). MMP-3 concentrations were significantly higher (adjusted odds ratio, ORadj 1.02 per ng/ml increase in concentration; p = 0.0004) and M-CSF significantly lower (ORadj 0.44 per ng/ml increase; p = 0.01) in PsA (pPsA and PsSpA combined) compared with PsC. Dkk-1 concentrations were significantly higher (ORadj 1.22 per ng/mL increase; p = 0.01), and OPG concentrations significantly lower (ORadj 0.20 per ng/mL increase; p = 0.02) in patients with axial arthritis (PsSpA and AS combined) than in those without (pPsA). Furthermore, Dkk-1 concentrations were significantly higher along a spectrum of increasing axial arthritis; Dkk-1 concentrations were higher in AS compared with PsSpA (ORadj 1.18 per ng/mL increase; p = 0.02). Receiver operating characteristic analysis showed MMP-3 to be the best single biomarker for differentiating PsA from PsC (AUC 0.70 for a cut-off of 14.51 ng/mL; sensitivity 0.76, specificity 0.60).CONCLUSIONS: MMP-3 and M-CSF are biomarkers for the presence of arthritis in psoriatic disease, and could therefore be used to screen for PsA in psoriasis cohorts. Dkk-1 and OPG are biomarkers of axial arthritis; they could therefore be used to screen for the presence of axial disease in PsA cases, and help differentiate PsSpA from AS. High concentrations of Dkk-1 in AS and PsSpA compared with HC, support previous reports that Dkk-1 is dysfunctional in the spondyloarthritides.

Objective Microparticles (MPs) are membrane-bound vesicles derived from vascular and intravascular cells such as endothelial cells (EMPs) and platelets (PMPs). We investigated EMP and PMP numbers across a spectrum of autoimmune rheumatic diseases (AIRDs) with the aim of comparing the levels of, and relationship between, EMPs and PMPs. Methods Patients with Systemic Lupus Erythematosus (SLE) (n = 24), Systemic Sclerosis (SSc) (n = 24), Primary Raynauds Phenomenon (RP) (n = 17) and “other CTD” (n = 15) (Primary Sjogrens Syndrome, UCTD or MCTD) as well as 15 healthy controls were recruited. EMPs and PMPs were quantified using flow cytometry. Associations between MP levels and objective functional vascular assessments were evaluated. Results SLE patients had significantly higher EMPs compared with healthy controls and SSc patients. Higher PMP levels were noted in SSc and primary RP when compared to healthy controls and ‘other CTD’ patients. A modest correlation was noted between EMP and PMP levels in healthy controls (Spearman r = 0.6, p = 0.017). This relationship appeared stronger in SLE (r = 0.72, p, Highlights • Levels of circulating EMPs and PMPs differ between SSc/primary RP compared with other CTDs including SLE. • Circulating MP levels are associated with objective assessments of macro- and microvascular dysfunction. • MPs may have a useful role as novel circulating biomarkers of vascular disease within the CTDs.

Objectives. Anti-tumour necrosis factor antibody (anti-TNF) has revolutionised the treatment of rheumatoid arthritis (RA) and remission is now a realistic possibility for patients. Despite widespread use of anti-TNFs, predicting which patients are most likely to attain a sustained good response to these treatments remains challenging. Our objective was to undertake a systematic review of the literature to evaluate existing evidence for demographic and clinical factors associated with the achievement of sustained remission in individuals with RA treated with anti-TNF. Methods. EMBASE, MEDLINE and the Cochrane Controlled Trials Register were searched along with studies identified from reference lists. Quality of studies was assessed using Newcastle-Ottawa criteria. Meta-analysis was undertaken where unadjusted odds ratios were available for the same demographic or clinical factors from at least three studies. Results. Six studies were identified. Concomitant methotrexate use was associated with an increased likelihood of achieving sustained remission. Greater baseline disease activity, tender joint count, age, disease duration, baseline functional impairment and female gender were associated with reduced likelihood of achieving sustained remission. Conclusions. Factors predicting sustained remission are seldom reported. Evidence identified in this review supports current recommendations for methotrexate co-prescription and highlights the negative impact of particular clinical and demographic features on the likelihood of achieving optimal response to anti-TNF treatment. Sustained remission is clinically more relevant than point remission in RA. More widespread reporting of sustained remission will help clinicians set realistic expectations on likely long-term treatment efficacy and could be an important tool for identifying patients suitable for dose optimisation. This article is protected by copyright. All rights reserved.

Innovative interventions that address the social determinants of health are required to help reduce persistent health inequalities. We argue that microcredit can act in this way and develop a conceptual framework from which to examine this. In seeking to evaluate microcredit this way we then examine how randomized controlled trials, currently considered as the ‘gold standard’ in impact evaluations of microcredit, compare with developments in thinking about study design in public health. This leads us to challenge the notion of trials as the apparent gold standard for microcredit evaluations and contend that the pursuit of trial-based evidence alone may be hampering the production of relevant evidence on microcredit’s public health (and other wider) impacts. In doing so, we introduce new insights into the global debate on microfinance impact evaluation, related to ethical issues in staging randomized controlled trials, and propose innovations on complementary methods for use in the evaluation of complex interventions.

Background:Since first described, our understanding of polymyositis (PM) has evolved substantially. Patients previously diagnosed with PM may now be better described as having an alternative diagnosis, including immune-mediated necrotizing myopathy (IMNM), connective tissue disease overlap myositis (CTD-OM), anti-synthetase syndrome (ASS) or inclusion body myositis (IBM).Objectives:To apply the current understanding of IIM subtypes to retrospectively review the diagnosis of patients classified as PM at our centre.Methods:We reviewed a cohort of 255 patients from a UK tertiary myositis clinic, with 37 patients classified as PM according to the EULAR/ACR IIM criteria and expert opinion (1). Consensus decisions made as to whether reclassification as an alternative IIM subtype would be appropriate in each case.Results:Thirty-seven patients with PM diagnosis according to EULAR/ACR IIM criteria and expert opinion were included in the analysis. Twenty-six patients (26/37, 68.4%) were female. The mean age at diagnosis was 57 years (SD 16.25) and mean follow up was 5.2 years (SD 4.8).After consensus discussions, ten patients (27%) retained classification as PM, representing 3.9% (10/255) of the original cohort of 255 patients. The remaining 27 were reclassified as follows: 7 CTD-OM (18.9%), 6 IMNM (16.2%), 6 unspecified myopathy (16.2%), 2 DM (5.4%), 1 IBM (2.7%), and 1 non-inflammatory myopathy (2.7%, myofibrillar myopathy). Four patients (10%) had insufficient data available to allow for a defined diagnosis.Of the 10 patients retaining classification as PM, 7 (70%) were female and mean age at diagnosis was 58.9 years. Clinical characteristics are represented in table 1. Mean CK at diagnosis was 2321 IU/L. Four patients (40%) were ANA positive, 8 patients (80%) were tested for the complete myositis antibody panel and 8 (80%) were specifically tested for the presence of HMGCR antibodies (figure 1). EMG revealed a myopathic pattern in 6/7 patients tested, while MRI demonstrated muscle oedema compatible with myositis in 3/5 of the patients that were tested. A complete muscle biopsy report was available in 8/10 PM-classified patients (80%), diffuse HLA-1 upregulation was present in 5 patients (50%), endomysial inflammatory infiltrates in 5 (50%) and perimysial infiltrates (in conjunction with endomysial infiltrates) in 3 (30%). No other specific features were found.Table 1.Clinical features.PM (n=10)CTD-OM (n=7)IMNM (n=6)All (n=37)Pyrexia0001 (2.7 %)Weight loss2 (20%)2 (28.6%)2 (33.3%)6 (16.2 %)Cutaneous rash01 (14.3%)02 (5.4 %)Mechanic’s hands1 (10%)2 (28.6%)04 (10.8 %)Sclerodactyly01 (14.3%)01 (2.7 %)Periungual erythema01 (14.3%)02 (5.3 %)Raynaud’s05 (71.4%)08 (21.6 %)Arthralgia05 (71.4%)08 (21.6 %)Arthritis02 (28.6%)05 (13.5 %)Muscle weakness10 (100%)7 (100%)6 (100%)36 (97.2%)Myalgia3 (30%)5 (71.4%)3 (50%)20 (54 %)Dysphagia3 (30%)5 (71.4%)1 (16.7%)13 (35.1 %)Interstitial lung disease (ILD)03 (42.9%)04 (10.5 %)Malignancy1 (9.1%)02 (33.3%)3 (8.1%)Conclusion:This study confirms that PM can now be considered a rare IIM subtype. A thorough examination, complete myositis antibody panel including HMGCR testing and careful interpretation of the biopsy results is recommended to accurately classify these patients.References:[1]Parker MJS, Oldroyd A, Roberts ME, Lilleker JB, Betteridge ZE, McHugh NJ, et al. The performance of the European League Against Rheumatism/American College of Rheumatology idiopathic inflammatory myopathies classification criteria in an expert-defined 10 year incident cohort. Rheumatol (United Kingdom). 2019 Mar 1;58(3):468–75Disclosure of Interests:None declared

ObjectivesTo compare the prevalence, clinical and radiographic characteristics of psoriatic spondyloarthritis (PsSpA) in psoriatic arthritis (PsA), with ankylosing spondylitis (AS).MethodsA prospective single-centre cross-sectional observational study recruited consecutive PsA and AS cases. Participants completed outcome measures, and underwent clinical examination, axial radiographic scoring and HLA-sequencing. Multivariable analyses are presented.ResultsThe 402 enrolled cases (201 PsA, 201 AS; fulfilling classification criteria for respective conditions) were reclassified based upon radiographic axial disease and psoriasis, as: 118 PsSpA, 127 peripheral-only PsA (pPsA), and 157 AS without psoriasis (AS) cases. A significant proportion of patients with radiographic axial disease had PsSpA (118/275; 42.91%), and often had symptomatically silent axial disease (30/118; 25.42%). Modified New York criteria for AS were fulfilled by 48/201 (23.88%) PsA cases, and Classification of Psoriatic Arthritis criteria by 49/201 (24.38%) AS cases. pPsA compared with PsSpA cases had a lower frequency of HLA-B*27 (OR 0.12; 95% CI 0.05 to 0.25). Disease activity, metrology and disability were comparable in PsSpA and AS. A significant proportion of PsSpA cases had spondylitis without sacroiliitis (39/118; 33.05%); they less frequently carried HLA-B*27 (OR 0.11; 95% CI 0.04 to 0.33). Sacroiliac joint complete ankylosis (adjusted OR, ORadj 2.96; 95% CI 1.42 to 6.15) and bridging syndesmophytes (ORadj 2.78; 95% CI 1.49 to 5.18) were more likely in AS than PsSpA. Radiographic axial disease was more severe in AS than PsSpA (Psoriatic Arthritis Spondylitis Radiology Index Score: adjusted incidence risk ratio 1.13; 95% CI 1.09 to 1.19).ConclusionsIn a combined cohort of patients with either PsA or AS from a single centre, 24% fulfilled classification criteria for both conditions. The pattern of axial disease was influenced significantly by the presence of skin psoriasis and HLA-B*27.

Objective.To assess whether the association between psoriatic nail dystrophy and radiographic damage in the hands of patients with psoriatic arthritis (PsA) is specific to the distal interphalangeal (DIP) joints.Methods.A convenience sample of patients was collated from the Bath longitudinal PsA cohort. All patients had PsA according to the ClASsification for Psoriatic ARthritis criteria (CASPAR) criteria, scored radiographs of their hands, and documented nail scores as measured by the Psoriatic Nail Severity Score. Chi-square tests were performed to examine for association between features of nail dystrophy and radiographic damage in the DIP joints, and proximal interphalangeal or metacarpophalangeal (non-DIP) joints of the corresponding digits.Results.There were 134 patients included, with a median age of 53 years (interquartile range; IQR 44–61) and disease duration of 7 years (IQR 3–17). The presence of any form of psoriatic nail dystrophy was associated with erosion at the DIP joints of the corresponding digit (OR 1.9, 95% CI 1.23–2.83; p < 0.004) and this association was primarily driven by the presence of nail onycholysis (OR 1.72; 95% CI 1.12–2.62; p = 0.02). Nail subungual hyperkeratosis was more strongly associated with joint space narrowing, erosions, and osteoproliferation at the corresponding DIP joint compared to non-DIP joints (p < 0.001). Nail pitting was not associated with erosions or osteoproliferation.Conclusion.The presence of psoriatic nail dystrophy, particularly onycholysis, is associated with erosive disease at the DIP joints. Subungual hyperkeratosis is more strongly associated with erosive damage at the DIP than non-DIP joints. These findings support the anatomical and pathological link between nail and DIP joint disease.

Objective.This analysis aimed to evaluate the economic burden of patients with psoriatic arthritis (PsA) on the UK healthcare system and estimate the relationship between functional status and direct healthcare costs.Methods.Functional status [measured using the Health Assessment Questionnaire–Disability Index (HAQ-DI)], demographics, disease history, and healthcare resource use data were extracted from a cohort of patients at the Royal National Hospital for Rheumatic Diseases, Bath, UK. Each resource use item per patient was then allocated a unit cost. Linear regression models were used to predict costs as a function of HAQ-DI. Medication costs were not included in the primary analysis, which was carried out from the UK National Health Service perspective.Results.Data were available for 101 patients. Mean HAQ-DI score was 0.84 (SD 0.75) and mean age at HAQ-DI measurement was 57.8 (SD 10.7). Total annual healthcare costs per patient, excluding medication costs, ranged between £174 and £8854, with a mean of £1586 (SD £1639). A 1-point increase in HAQ-DI score was associated with an increase in total costs of £547.49 (standard error £224), with secondary care consultations appearing to be the primary factor. Subgroup analyses suggested higher cost increases in patients with HAQ-DI scores of 2–3 and with a disease duration > 10 years.Conclusion.Patients with PsA place a significant economic burden on the healthcare system. Functional status is highly correlated with costs and appears to be driven mainly by the cost of secondary care consultations. Results were similar to previous studies in rheumatoid arthritis populations.

Objectives To characterise the 10 year relationship between anti-transcriptional intermediary factor 1 antibody (anti-TIF1-Ab) positivity and cancer onset in a large UK-based adult dermatomyositis (DM) cohort. Methods Data from anti-TIF1-Ab positive/negative adults with verified diagnoses of DM from UKMYONET were analysed. Each patient was followed up until they developed cancer. Kaplan-Meier methods and Cox-proportional hazard modelling were employed to estimate cumulative cancer incidence. Results Data from 263 DM cases were analysed, with a total of 3,252 person-years and a median 11 years follow-up; 55 (21%) of DM cases were anti-TIF1-Ab positive. After 10 years of follow up, a higher proportion of anti-TIF1-Ab positive cases developed cancer, compared with anti-TIF1-Ab negative cases: 38% vs 15% (hazard ratio 3.4 [95% CI 2.2, 5.4]). All the detected malignancy cases in the anti-TIF1-Ab positive cohort occurred between 3 years prior to and 2.5 years after DM onset. No cancer cases were detected within the following 7.5 years in this group, whereas cancers were detected during this period in the anti-TIF1-Ab negative cases. Ovarian cancer was more common in the anti-TIF1-Ab positive vs negative cohort – 19% versus 2% respectively (p-value

Aims To evaluate the relationship between expression of myxovirus-resistance protein A (MxA) protein on muscle biopsies by immunohistochemistry and disease activity in juvenile dermatomyositis (JDM) patients. Also, another aim was to investigate whether the expression of MxA is related with myositis-specific autoantibodies (MSA) status in JDM patients. Methods 103 patients (median aged 6.3, interquartile range 0.5-15.9) enrolled in the Juvenile Dermatomyositis Cohort and Biomarker Study (JDCBS). Muscle biopsies were stained with MxA and scored. Clinical data at initial presentation were collected and autoantibodies were analysed. Multiple linear regression analysis was performed to estimate the association between MxA expression on muscle fibres and muscle disease activity, and MSA status. Results Expression of MxA protein on JDM samples was identified in 61.2%. There was a significant association between MxA scores and Childhood Myositis Assessment Scale (CMAS) (P = 0.002), and Manual Muscle Testing of Eight Muscles (MMT8) (P = 0.026). CMAS and MMT8 scores were significantly lower in the group of patients with strong MxA expression. MxA scores differed according to MSA subgroups (P = 0.002). Patients with positive nuclear matrix protein 2 autoantibodies had strong MxA expression, whereas anti-melanoma differentiation-associated gene 5 positive patients had no or weak MxA expression. Conclusions This study reveals the significant association between level of MxA expression on muscle fibres and clinical measures of muscular disease activity in JDM patients and MSA status. This confirms type I interferonopathies in muscle fibres of JDM patients which could help with improving treatment outcome in JDM patients and underscoring the distinct pathophysiological pathways in different MSA status.

Background: SLE may be stratified according to a range of different immune assessments but the relationships between these are less well defined. MASTERPLANS is an MRC-funded consortium that seeks to identify immunophenotypic subgroups of patients that predict response to therapy. Objectives: Our objective here was to analyse a clinically well-phenotyped patients using a suite of immune assessments and identify inter-relationships between these features as well as subgroups of patients who may differ in response to therapy. Methods: 143 SLE patients were evaluated for clinical phenotype using BILAG-2004, autoantibodies using radioimmunoprecipitation (IP, University of Bath), two interferon scores (IFN-Score-A and IFN-Score-B), flow cytometry for major circulating immune cell subsets, as well as the surface protein expression of tetherin on each subset, a cell-specific assay for IFN response. Unsupervised hierarchical clustering was used to define autoantibody subgroups. IFN scores (reflected dCT) were compared between the groups using multivariate models. Other variables were compared using Kruskal-Wallis test with pairwise comparisons. Results: Using IP, 141 patients could be divided into five subgroups: U1RNP/Sm+ only (n=23), Ro60+ only (n=8), U1RNP/Sm+Ro60+ (n=6), Ro60+Ro52+La+ (n=11), Ro52+ (n=16) and other ANA (n=77). Antibody subgroups was strongly associated with IFN-Score-A (F=4.39, p=0.001). Expression was lowest for “other ANA”, intermediate for single antibody groups, and highest with multiple positive antibodies. Multivariate linear regression, including interaction terms between antibody types, revealed that Ro60 and U1RNP/Sm were the independent predictors of IFN-Score-A level (p=0.051 and 0.009 respectively). There was no association between autoantibody status and IFN-Score-B (F=0.973, p=0.438). In flow cytometry, the U1RNP/Sm group was notable for significantly lower numbers of CD4-T-cells and memory-B-cells. Memory -B-cells were also lower in antibody-positive groups compared to “other ANA”. Tetherin expression was increased in antibody positive groups, but to a similar extent on most cell subsets. Memory B cell tetherin was significantly higher in the groups with multiple positive antibodies. U1RNP/Sm+ was associated with renal involvement (p=0.004). Mucocutaneous involvement was greater in the Ro60+Ro52+La+ group (p=0.037). Conclusion: This cohort revealed relationships between immune features. U1RNP/Sm antibody was notable for defining a group of patients with a cluster of immune abnormalities, including the greatest elevation of IFN activity, greater abnormalities on flow cytometry and clinical renal involvement. This was independent to the IFN-Score-B high status that predicts better clinical response to rituximab (presented elsewhere at this conference). Future work in MASTERPLANS will investigate the significance of these subgroups for response to therapy. Disclosure of Interests: Marta Aguilar-Zamora: None declared, Hui Lu: None declared, Zoe Betteridge: None declared, Katie Dutton: None declared, Md Yuzaiful Md Yusof: None declared, Antonios Psarras: None declared, The MASTERPLANS Consortium. : None declared, Neil McHugh: None declared, Edward Vital Grant/research support from: He has received honoraria and research grant support from Roche, GSK and AstraZeneca.

Objectives PsA is an inflammatory condition that can cause pain, fatigue, swelling and joint stiffness. The consequences include impaired physical function, a high psychosocial burden, reduced quality of life and work disability. The presenting symptoms can be non-specific and varied, leading to delays in diagnosis or referral to specialist teams. The aim of this study was to explore patients' experiences of being diagnosed and the initial management of PsA. Methods The study used a qualitative design, with data collected in one-to-one, face-to-face semi-structured interviews. Results Fifteen newly diagnosed patients ( Conclusion Participants were already dealing with functional limitations and were highly distressed and anxious by the time they received their diagnosis. Physical and mental outcomes could be improved by the implementation of existing psoriasis management guidelines and strategies for earlier referral from primary care to rheumatology and by the development of guidelines on educational, self-management and psychological support provision soon after diagnosis.

ObjectivesTo report on fatigue in patients from the United Kingdom primary Sjögren’s syndrome (pSS) registry identifying factors associated with fatigue and robust to assignable causes such as comorbidities and medications associated with drowsiness.MethodsFrom our cohort (n = 608), we identified those with comorbidities associated with fatigue, and those taking medications associated with drowsiness. We constructed dummy variables, permitting the contribution of these potentially assignable causes of fatigue to be assessed. Using multiple regression analysis, we modelled the relationship between Profile of Fatigue and Discomfort physical and mental fatigue scores and potentially related variables.ResultsPain, depression and daytime sleepiness scores were closely associated with both physical and mental fatigue (all p ≤ 0.0001). In addition, dryness was strongly associated with physical fatigue (p ≤ 0.0001). These effects were observed even after adjustment for comorbidities associated with fatigue or medications associated with drowsiness.ConclusionsThese findings support further research and clinical interventions targeting pain, dryness, depression and sleep to improve fatigue in patients with pSS.This finding is robust to both the effect of other comorbidities associated with fatigue and medications associated with drowsiness.

Background SLE may be stratified according to a range of different immune assessments but the relationships between these are less well defined. MASTERPLANS is an MRC-funded consortium that seeks to identify immunophenotypic subgroups of patients that predict response to therapy. Our objective here was to analyse a clinically well-phenotyped patients using a suite of immune assessments and identify inter-relationships between these features as well as subgroups of patients who may differ in response to therapy. Methods 143 SLE patients were evaluated for clinical phenotype using BILAG-2004, autoantibodies using radioimmunoprecipitation (IP, University of Bath), two interferon scores (IFN-Score-A and IFN-Score-B), flow cytometry for major circulating immune cell subsets, as well as the surface protein expression of tetherin on each subset, a cell-specific assay for IFN response. Unsupervised hierarchical clustering was used to define autoantibody subgroups. IFN scores (reflected dCT) were compared between the groups using multivariate models. Other variables were compared using Kruskal-Wallis test with pairwise comparisons. Results Using IP, 141 patients could be divided into five subgroups: U1RNP/Sm+only (n=23), Ro60 +only (n=8), U1RNP/Sm+Ro60+ (n=6), Ro60 +Ro52+La+(n=11), Ro52+ (n=16) and other ANA (n=77). Antibody subgroups was strongly associated with IFN-Score-A (F=4.39, p=0.001). Expression was lowest for other ANA, intermediate for single antibody groups, and highest with multiple positive antibodies. Multivariate linear regression, including interaction terms between antibody types, revealed that Ro60 and U1RNP/Sm were the independent predictors of IFN-Score-A level (p=0.051 and 0.009 respectively). There was no association between autoantibody status and IFN-Score-B (F=0.973, p=0.438). In flow cytometry, the U1RNP/Sm group was notable for significantly lower numbers of CD4-T-cells and memory-B-cells. Memory -B-cells were also lower in antibody-positive groups compared to other ANA. Tetherin expression was increased in antibody positive groups, but to a similar extent on most cell subsets. Memory B cell tetherin was significantly higher in the groups with multiple positive antibodies. U1RNP/Sm+was associated with renal involvement (p=0.004). Mucocutaneous involvement was greater in the Ro60 +Ro52+La+ group (p=0.037). Conclusions This cohort revealed relationships between immune features. U1RNP/Sm antibody was notable for defining a group of patients with a cluster of immune abnormalities, including the greatest elevation of IFN activity, greater abnormalities on flow cytometry and clinical renal involvement. This was independent to the IFN-Score-B high status that predicts better clinical response to rituximab (presented elsewhere at this conference). Future work in MASTERPLANS will investigate the significance of these subgroups for response to therapy. Funding Source(s): Medical Research Council, National Institute for Health Research