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Background:There is a widening health divide in the UK despite health inequalities being a longstanding subject of policy and research. New types of evidence are needed. Key points for discussion:Knowledge of public values for non-health policies and their associated (non-)health outcomes is currently missing from decision-making processes. Eliciting public values using stated preference techniques can provide insights on what the general public would be willing to give up for different distributions of (non-)health outcomes and the policies that can achieve them. To understand the role this evidence could have in decision-making processes, Kingdon’s multiple streams analysis (MSA) is used as a policy lens to explore how evidence of public values could affect policy processes for ways to tackle health inequalities. Conclusions and implications:This paper outlines how evidence of public values could be elicited through the use of stated preference techniques and suggests this could facilitate the creation of policy windows for tackling health inequalities. Additionally, Kingdon’s MSA helps make explicit six crosscutting issues when generating this new form of evidence. This suggests the need to explore reasons for public values and how decision makers would use such evidence. With an awareness of these issues, evidence on public values has the potential to support upstream policies to tackle health inequalities.

Objectives HCQ and AZA are used to control disease activity and reduce risk of flare during pregnancy in patients with SLE. The aim of this study was to determine the outcomes of children born to mothers with SLE exposed to HCQ or AZA during pregnancy and breast-feeding. Methods Women attending UK specialist lupus clinics with children ≤17 years old, born after SLE diagnosis, were recruited to this retrospective study. Data were collected using questionnaires and from clinical record review. Factors associated with the outcomes of low birth weight and childhood infection were determined using multivariable mixed-effects logistic regression models. Results We analysed 284 live births of 199 mothers from 10 UK centres. The first pregnancies of 73.9% of mothers (147/199) were captured in the study; (60.4%) (150/248) and 31.1% (87/280) children were exposed to HCQ and AZA, respectively. There were no significant differences in the frequency of congenital malformations or intrauterine growth restriction between children exposed or not to HCQ or AZA. AZA use was increased in women with a history of hypertension or renal disease. Although AZA was associated with low birth weight in univariate models, there was no significant association in multivariable models. In adjusted models, exposure to AZA was associated with increased reports of childhood infection requiring hospital management [odds ratio 2.283 (1.003, 5.198), P = 0.049]. Conclusions There were no significant negative outcomes in children exposed to HCQ in pregnancy. AZA use was associated with increased reporting of childhood infection, which warrants further study.

OBJECTIVE: To compare the responsiveness of the British Isles Lupus Assessment Group 2004 index (BILAG-2004) and the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) disease activity indices and to determine whether there was any added value in combining BILAG-2004, BILAG-2004 system tally (BST), or simplified BST (sBST) with SLEDAI-2K. METHODS: This was a multicenter longitudinal study of SLE patients. Data were collected on BILAG-2004, SLEDAI-2K, and therapy on consecutive assessments in routine practice. The external responsiveness of the indices was assessed by determining the relationship between change in disease activity and change in therapy between 2 consecutive visits. Comparison of indices and their derivatives was performed by assessing the main effects of the indices using logistic regression. Receiver operating characteristic curves analysis was used to describe the performance of these indices individually and in various combinations, and comparisons of area under the curve were performed. RESULTS: There were 1,414 observations from 347 patients. Both BILAG-2004 and SLEDAI-2K maintained an independent relationship with change in therapy when compared. There was some improvement in responsiveness when continuous SLEDAI-2K variables (change in score and score of previous visit) were combined with BILAG-2004 system scores. Dichotomization of BILAG-2004 or SLEDAI-2K resulted in poorer performance. BST and sBST had similar responsiveness as the combination of SLEDAI-2K variables and BILAG-2004 system scores. There was little benefit in combining SLEDAI-2K with BST or sBST. CONCLUSION: The BILAG-2004 index had comparable responsiveness to SLEDAI-2K. There was some benefit in combining both indices. Dichotomization of BILAG-2004 and SLEDAI-2K leads to suboptimal performance. BST and sBST performed well on their own; sBST is recommended for its simplicity and clinical meaningfulness.

Background/Aims After cardiopulmonary disease, cancer accounts for the highest proportion of deaths in systemic sclerosis (SSc), exceeding deaths attributed to renal disease and/or infection. Few population-based studies have assessed the burden of cancer in SSc. The present study investigated the association between cancer and SSc using the Clinical Practice Research Datalink (CPRD). Methods A validated case ascertainment strategy using combinations of diagnostic Read codes was applied to identify SSc patients in the CPRD with >12 months of data within the time period 01/01/1998 to 31/12/2017. A cohort study design examined cancer occurrence following a diagnosis of SSc. Patients with SSc were matched to six non-SSc comparators by age, sex and GP practice using incident density sampling. Prevalent and incident cases of SSc were analysed separately. Information on date and type of diagnosis of cancer was recorded. Descriptive statistics and Cox analyses determined hazard ratios for cancer occurrence. Results From 10.1 million individuals in the CPRD, 1,588 of cases of SSc were identified (85.3% female). We identified 206 cancers that occurred following a diagnosis of SSc (116 in prevalent cohort and 90 amongst incident cohort) (Table). The three commonest cancers were mucocutaneous (4.5%), lung (2.1%) and breast (1.9%). Lung cancer was significantly more common in SSc (Table). Incidence of cancer was higher in SSc (17 vs. 13.8 per 1000 person years) with adjusted hazard ratios of 1.41 (95% CI 1.14-1.75) for prevalent cases and 1.32 (95% CI 1.04-1.67) for incident SSc cases. We did not identify a strong relationship between cancer occurrence and SSc onset. Incidence of cancer increased with age at SSc diagnosis and was higher in males. Death from any cause at 6 months was higher in patients with SSc and cancer. Conclusion We have identified an increased risk of cancer occurrence (primarily mucocutaneous and lung) in patients with SSc from the UK, particularly amongst males and patients with higher age at SSc diagnosis. These findings could support screening recommendations for cancer in SSc. Disclosure J.D. Pauling: Consultancies; Astra Zenaca, Janssen, Permeatus Inc., Sojournix Pharma, Boehringer Ingelheim. Honoraria; Janssen. Member of speakers’ bureau; Janssen. J. Snowball: None. N. McHugh: None. A. McGrogan: None.

Objective To determine whether BILAG-2004 index is associated with the development of damage in a cohort of SLE patients. Mortality and development of damage were examined. Methods This was a multicentre longitudinal study. Patients were recruited within 12 months of achieving fourth ACR classification criterion for SLE. Data were collected on disease activity, damage, SLE-specific drug exposure, cardiovascular risk factors, antiphospholipid syndrome status and death at every visit. This study ran from 1 January 2005 to 31 December 2017. Descriptive statistics were used to analyse mortality and development of new damage. Poisson regression was used to examine potential explanatory variables for development of new damage. Results A total of 273 SLE patients were recruited with total follow-up of 1767 patient-years (median 73.4 months). There were 6348 assessments with disease activity scores available for analysis. During follow-up, 13 deaths and 114 new damage items (in 83 patients) occurred. The incidence rate for development of damage was higher in the first 3 years before stabilizing at a lower rate. Overall rate for damage accrual was 61.1 per 1000 person-years (95% CI: 50.6, 73.8). Analysis showed that active disease scores according to BILAG-2004 index (systems scores of A or B, counts of systems with A and BILAG-2004 numerical score) were associated with development of new damage. Low disease activity (LDA) states [BILAG-2004 LDA and BILAG Systems Tally (BST) persistent LDA] were inversely associated with development of damage. Conclusions BILAG-2004 index is associated with new damage. BILAG-2004 LDA and BST persistent LDA can be considered as treatment targets.

(1) Background: Myositis specific antibodies (MSA) are important diagnostic biomarkers. Among the rarest and most challenging MSA are anti-OJ antibodies which are associated with anti-synthetase syndrome (ASS). In contrast to the other tRNA synthetases that are targets of ASS autoantibodies (e.g Jo-1, PL-7, PL-12, EJ, KS, Zo), OJ represents a macromolecular complex with several ribonucleoprotein subunits. Therefore, the choice of the antigen in autoantibody assays can be challenging. (2) Methods: We collected two independent cohorts with anti-OJ antibodies, one based on a commercial line immunoassay (LIA) (n = 39), the second based on protein immunoprecipitation (IP) (n = 15). Samples were tested using a particle-based multi-analyte technology (PMAT) system that allows for the simultaneous detection of antibodies to various autoantigens. For the detection of anti-OJ antibodies, two different antigens were deployed (KARS, IARS) on PMAT. The reactivity to the two antigens KARS and IARS was analyzed individually and combined in a score (sum of the median fluorescence intensities). (3) Results: In the cohort selection based on LIA, 3/39 (7.7%) samples were positive for anti-KARS and 7/39 (17.9%) for anti-IARS and 14/39 (35.9%) when the two antigens were combined. In contrast, in samples selected by IP the sensitivity of anti-KARS was higher: 6/15 (40.0%) samples were positive for anti-KARS, 4/15 (26.7%) for anti-IARS and 12/15 (80.0%) for the combination of the two antigens. 18/39 (46.2%) of the LIA samples generated a cytoplasmic IIF pattern (compatible with anti-synthetase antibodies), but there was no association with the antibody levels, neither with LIA nor with PMAT. (4) Conclusions: The combination of IARS and KARS might represent a promising approach for the detection of anti-OJ antibodies on a fully automated platform.

The idiopathic inflammatory myopathies (IIM) are heterogeneous diseases, thought to be initiated by immune activation in genetically predisposed individuals. In this study we imputed variants from the Immunochip array using a large reference panel to fine-map associations and identify novel associations in IIM.We analysed 2,565 Caucasian IIM samples collected through the Myositis Genetics Consortium (MYOGEN) and 10,260 ethnically-matched controls. We imputed 1,648,116 variants from the Immunochip array using the Haplotype Reference Consortium panel and conducted association analysis on IIM, and clinical and serological subgroups.The human leukocyte antigen (HLA) locus was consistently the most significantly associated region. Four non-HLA regions reached genome-wide significance, three in the whole IIM cohort (SDK2 and LINC00924 - both novel, and STAT4), with evidence of independent variants in STAT4, and NAB1 in the polymyositis (PM) subgroup. We also found suggestive evidence of association with loci previously associated with other autoimmune rheumatic diseases (TEC and LTBR). We identified more significant associations than those previously reported in IIM, for STAT4 and DGKQ in the total cohort, for NAB1 and FAM167A-BLK loci in PM, and CCR5 in inclusion body myositis. We found enrichment of variants among DNase I hypersensitivity sites and histone marks associated with active transcription within blood cells.We report novel and strong associations in IIM and PM, and localise signals to single genes and immune cell types. This article is protected by copyright. All rights reserved.

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

Gene expression profiles are associated with the clinical heterogeneity of SLE but are not well studied as biomarkers for therapy. Many clinical and demographic features influence treatment responses. We studied gene expression and response to rituximab in a multi-ethnic UK cohort refractory to standard therapy.Baseline expression of transcripts known to associate with clinical features of SLE was evaluated in whole blood by 96-probe Taqman® array in patients (n=213) with active SLE, prospectively enrolled in British Isles Lupus Assessment Group (BILAG) Biologics Registry. Autoantibodies were measured using immunoprecipitation and ELISA. Response to first cycle rituximab (n=110) was determined by BILAG-2004 criteria at 6 months.Interferon scores were lower in European ancestry patients than all other groups. The relationship between blood interferon scores and plasmablast, neutrophil, myeloid, inflammation and erythropoiesis-annotated scores differed between patients of European and non-European ancestries. Hierarchical clustering revealed 3 distinct non-European ancestry patient subsets with stratified response to rituximab which was not explained by sociodemographic and clinical variables. Response was lowest in an interferon-low, neutrophil-high cluster and highest in a cluster with high expression across all signatures (p0.001). Clusters within European ancestry patients did not predict response to rituximab but segregated patients by global disease activity and renal involvement. In both ancestral groups, interferon-high clusters associated with U1RNP-Sm antibodies.Ancestry appears central to the immunological and clinical heterogeneity in SLE. These results suggest that ancestry, disease activity and transcriptional signatures could each assist predict the effectiveness of B-cell depletion. This article is protected by copyright. All rights reserved.

Objectives The aim of this study was to explore the use of Bayesian networks (BNs) to understand the relationships between musculoskeletal symptoms and the development of PsA in people with psoriasis. Methods Incident cases of psoriasis were identified for 1998 to 2015 from the UK Clinical Research Practice Datalink. Musculoskeletal symptoms (identified by Medcodes) were concatenated into primary groups, each made up of several subgroups. Baseline demographics for gender, age, BMI, psoriasis severity, alcohol use and smoking status were also extracted. Several BN structures were composed using a combination of expert knowledge and data-oriented modelling based on: (i) primary musculoskeletal symptom groups; (ii) musculoskeletal symptom subgroups and (iii) demographic variables. Predictive ability of the networks using the area under the receiver operating characteristic curve was calculated. Results Over one million musculoskeletal symptoms were extracted for the 90 189 incident cases of psoriasis identified, of which 1409 developed PsA. The BN analysis yielded direct relationships between gender, BMI, arthralgia, finger pain, fatigue, hand pain, hip pain, knee pain, swelling, back pain, myalgia and PsA. The best BN, achieved by using the more site-specific musculoskeletal symptom subgroups, was 76% accurate in predicting the development of PsA in a test set and had an area under the receiver operating characteristic curve of 0.73 (95% CI: 0.70, 0.75). Conclusion The presented BN model may be a useful method to identify clusters of symptoms that predict the development of PsA with reasonable accuracy. Using a BN approach, we have shown that there are several symptoms which are predecessors of PsA, including fatigue, specific types of pain and swelling.

Objective.To determine the risk of a diagnosis of osteoarthritis (OA) in patients with psoriatic arthritis (PsA) compared to patients with psoriasis and a general population cohort.Methods.Incident PsA patients aged 18–89 years at diagnosis were identified from the United Kingdom Clinical Practice Research Datalink between 1998 and 2014. All patients with PsA were matched to 2 cohorts of patients, both at a 1:4 ratio. The first cohort included patients with psoriasis (and no PsA) and the second was a general population cohort (with no psoriasis or PsA). The baseline prevalence of OA was calculated for each study cohort. The incidence of OA was calculated, and adjusted relative risks (RRadj) were calculated using conditional Poisson regression.Results.We identified 6783 incident PsA patients. The baseline prevalence of OA ranged from 22.1% (95% CI 21.1–23.1) in the PsA cohort to 12.6% (95% CI 12.2–13.0) and 11.0% (95% CI 10.6–11.3) in the psoriasis and general population cohorts, respectively. The incidence of OA was significantly higher in the PsA cohort compared to the psoriasis and general population cohorts after adjusting for BMI (RRadj 1.68, 95% CI 1.46–1.93, and RRadj 1.86, 95% CI 1.62–2.14, respectively).Conclusion.An increased risk of OA was observed in patients with PsA compared to patients with psoriasis alone and those in the general population. Further work is needed to determine whether this reflects a true increase in OA risk or misdiagnosed PsA, and the extent to which it can be explained by differences in the opportunity for OA diagnosis between cohorts.

Objectives Uncertainty around clinical heterogeneity and outcomes for patients with JDM represents a major burden of disease and a challenge for clinical management. We sought to identify novel classes of patients having similar temporal patterns in disease activity and relate them to baseline clinical features. Methods Data were obtained for n = 519 patients, including baseline demographic and clinical features, baseline and follow-up records of physician’s global assessment of disease (PGA), and skin disease activity (modified DAS). Growth mixture models (GMMs) were fitted to identify classes of patients with similar trajectories of these variables. Baseline predictors of class membership were identified using Lasso regression. Results GMM analysis of PGA identified two classes of patients. Patients in class 1 (89%) tended to improve, while patients in class 2 (11%) had more persistent disease. Lasso regression identified abnormal respiration, lipodystrophy and time since diagnosis as baseline predictors of class 2 membership, with estimated odds ratios, controlling for the other two variables, of 1.91 for presence of abnormal respiration, 1.92 for lipodystrophy and 1.32 for time since diagnosis. GMM analysis of modified DAS identified three classes of patients. Patients in classes 1 (16%) and 2 (12%) had higher levels of modified DAS at diagnosis that improved or remained high, respectively. Patients in class 3 (72%) began with lower DAS levels that improved more quickly. Higher proportions of patients in PGA class 2 were in DAS class 2 (19%, compared with 16 and 10%). Conclusion GMM analysis identified novel JDM phenotypes based on longitudinal PGA and modified DAS.

Background/Aims Anti-synthetase syndrome (ASS) represents a distinct entity within myositis spectrum disorders; however, correct classification of patients with anti-tRNA synthetase autoantibodies and skin manifestations akin to dermatomyositis (DM) remains uncertain. Our aim was to compare clinical characteristics, skin involvement, and malignancy, between patients with ASS and DM, classified by disease-specific autoantibodies. Methods Data from 05/2009-03/2016 from 9 countries from the prospective, myositis EuroMyositis registry were downloaded. Those with anti-tRNA synthetase autoantibodies (Jo-1/PL-7/PL-12/OJ/EJ/KS) were classified as ASS, and those with Mi-2/TIF1-γ/NXP2/SAE/MDA5 autoantibodies as DM. Clinical phenotypes including malignancies (except skin malignancies) were tabulated. Characteristics of patients with skin involvement (excluding mechanic’s hands and Raynaud’s phenomenon) were compared using Fisher’s exact test with Bonferroni corrected p-values. Results Of 3,067 patients, 2,028 had autoantibody profiling results (66.1%), of which 783 (38.6%) were positive for at least one of the autoantibodies being considered. Five patients with dual autoantibody specificities were excluded. Of the remaining 778, 320 (41.1%) were classified as DM, and 458 (58.9%) as ASS. Median age at diagnosis was 48.2 years (interquartile range [IQR] 37.5 to 57.8) in the DM cohort and 49 (IQR 38.3 to 62.2) in the ASS cohort. Skin involvement was present in 277 (86.6%) DM patients (DM skin) vs 204 (44.5%) ASS patients (ASS skin) (pcorr Conclusion Patients with ASS have frequent skin involvement but also a distinct clinical phenotype compared to DM. These findings may inform the development of future classification criteria for ASS. Disclosure R.M. Hum: None. J.B. Lilleker: None. J.A. Lamb: None. W.E. Ollier: None. G. Wang: None. L.R. Wedderburn: None. L.P. Diederichsen: None. J. Schmidt: None. P. Oakley: None. O. Benveniste: None. M.G. Danieli: None. K. Danko: None. N.T.P. Thuy: None. M.V.D. Mercado: None. H. Andersson: None. B.D. Paepe: None. J.L.D. Bleecker: None. B. Maurer: None. L.J. McCann: None. N. Pipitone: None. N. McHugh: None. P. New: None. J. Vencovsky: None. I.E. Lundberg: None. H. Chinoy: None.

Background/Aims Idiopathic inflammatory myopathies (IIM) are multisystem diseases characterised by muscle inflammation. Over 60% of patients with IIM have a myositis-related autoantibody. Our laboratory specialises in autoantibody testing. We offer an extended spectrum autoantibody testing diagnostic service and have also screened over 3000 myositis patients enrolled in research studies for the presence of autoantibodies. We noticed a recurring pattern following K562 cell radio-immunoprecipitation that was present in several myositis patient sera and in a handful of samples that came to us via the diagnostic service. We set out to determine the antigenic target of this novel autoantibody. Methods We have previously screened 1319 serum/plasma samples from IIM patients enrolled in the UKMyoNet and 380 from patients with juvenile onset IIM enrolled in the JDCBS for autoantibodies by immunoprecipitation. Additional cohorts similarly investigated include >150 healthy control sera and >400 SLE patient sera. Patients with the novel autoantibody of interest were identified by a distinctive 120kDa band associated with a ‘smear’ on autoradiography following K562 cell immunoprecipitation and separation of autoantigens by SDS PAGE. ESI-QTOF mass spectrometry was used to identify the antigenic target in an example serum. Using a commercial anti-PARP1 antibody as a control, western blotting of K562 and PARP1 overexpressed cell lysate was used to confirm the antigenic target in remaining samples of interest. Indirect immunofluorescence was performed on HEp-2 cells according to manufacturers’ instructions. Results 11 patient samples were identified as having the 120 complex ‘smear’ pattern of interest: six had been received via the diagnostic service and five were enrolled in UKMyoNet. Prevalence in the UKMyoNet cohort was 0.4%. Mass spectrometry identified PARP1 as the antigenic target. This was confirmed in all remaining samples by western blot. Table 1 shows available clinical data. Conclusion PARP1 is an autoantigen target in myositis patients in addition to those with other rheumatic diseases. Where data was available, patients with anti-PARP1 had features suggesting an anti-synthetase syndrome phenotype, but this may primarily relate to the other autoantibodies present. Further work is needed to determine the prevalence of anti-PARP1 in other cohorts and its clinical associations. Disclosure V. Riddell: Grants/research support; Bath Institute of Rheumatic Disease. Z. Betteridge: None. E. Bowler: None. H. Chinoy: None. P. Gordon: None. L. Wedderburn: None. S. Bagby: None. N. Mchugh: None. S. Tansley: None.

Objectives: This study aimed to demonstrate how to estimate the value of health gain after patients with a multisystem disease achieve a condition-specific composite response endpoint. Methods: Data from patients treated in routine practice with an exemplar multisystem disease (systemic lupus erythematosus) were extracted from a national register (British Isles Lupus Assessment Group Biologics Register). Two bespoke composite response endpoints (Major Clinical Response and Improvement) were developed in advance of this study. Difference-in-differences regression compared health utility values (3-level version of EQ-5D; UK tariff) over 6 months for responders and nonresponders. Bootstrapped regression estimated the incremental quality-adjusted life-years (QALYs), probability of QALY gain after achieving the response criteria, and population monetary benefit of response. Results: Within the sample (n = 171), 18.2% achieved Major Clinical Response and 49.1% achieved Improvement at 6 months. Incremental health utility values were 0.0923 for Major Clinical Response and 0.0454 for Improvement. Expected incremental QALY gain at 6 months was 0.020 for Major Clinical Response and 0.012 for Improvement. Probability of QALY gain after achieving the response criteria was 77.6% for Major Clinical Response and 72.7% for Improvement. Population monetary benefit of response was £1 106 458 for Major Clinical Response and £649 134 for Improvement. Conclusions: Bespoke composite response endpoints are becoming more common to measure treatment response for multisystem diseases in trials and observational studies. Health technology assessment agencies face a growing challenge to establish whether these endpoints correspond with improved health gain. Health utility values can generate this evidence to enhance the usefulness of composite response endpoints for health technology assessment, decision making, and economic evaluation.

PURPOSE OF REVIEW: To provide an overview of recent discoveries related to myositis-specific autoantibodies (MSAs) and assays used for their measurement.RECENT FINDINGS: New autoantibody specificities have been reported including a MSA directed against eukaryotic initiation factor 3 and a myositis-associated autoantibody directed against heat shock factor 1. The association of anti-TIF1γ with cancer-associated dermatomyositis dependent on age has been confirmed in several large cohorts. Despite MSAs being almost entirely mutually exclusive, several myositis autoantigens are overexpressed in regenerating muscle and do not correlate with the corresponding MSA in any one patient. Further mechanisms may determine the final MSA specificity and are likely to include the need for autoantigen processing and presentation with adaptive T-cell help. The presence of CD4-positive T cells specific for histidyl tRNA synthetase protein in bronchial lavage fluid from antisynthetase patients lends support to this view. Finally, it is widely held that MSA do play an important role in clinical practice among some evidence and concern about commercial assay reliability.SUMMARY: MSAs continue to provide important tools for clinical diagnosis and management as well as insights into disease mechanisms. Further improvement in the standardization and reliability of routine detection of MSAs is a high priority.

Objective. Improving the assessment of psoriatic arthritis (PsA) is a key purpose of the Group for Research and Assessment of Psoriasis and PsA (GRAPPA). Herein, we report the proceedings of the GRAPPA composites workshop at the 2019 GRAPPA annual meeting and the membership’s recommended next steps. Methods. A review of continuous composite measures was conducted in an introductory workshop, followed by 10 breakout group sessions and a final plenary session for feedback and voting. Results. Participants included 154 members: 87 rheumatologists, 18 dermatologists, 2 rheumatologist/dermatologists, 12 patient research partners, 14 academics, 1 methodologist, and 20 industry members. Of voting members, 88.8% agreed a need exists for a continuous composite measure for routine practice, but only 62% were currently using a composite measure. Of these, 27% were using the 28-joint count Disease Activity Score (DAS), which is not a PsA-specific measure; 20% were using a PsA-specific measure such as PsA DAS (PASDAS), Composite Psoriatic Disease Activity Index (CPDAI), or Disease Activity Index for PsA (DAPSA). Members agreed that the existing measures were not feasible in their current forms (CPDAI 83%, PASDAS 82%, and DAPSA 47%) and that modification should be tested. The majority (76%) agreed that disease effect should be measured separately from disease activity. Conclusion. The GRAPPA membership supports the need for a continuous composite measure of disease activity for use in routine clinical care, the separate measurement of disease effect and activity, and the testing of modifications to candidate instruments rather than the development of new measures.

Financially vulnerable, low-income individuals are more likely to experience financial exclusion as they are unable to access financial services that meet their needs. How do they cope with economic instability, and what is the role of social networks in their coping strategies? Using financial diaries, we explore the day-to-day monetary transactions (n = 16,889) of forty-five low-to-moderate income individuals with restricted access to mainstream lending in Glasgow, UK, over a six-month period. Our sample includes users of microcredit and financial advice, as well as nonusers of these services. Findings reveal that informal lending to avoid the pernicious effects of short-term illiquidity was pervasive among these individuals. However, taking informal loans often strains valuable social capital and keeps people from building up a formal credit footprint. Our findings suggest that financially vulnerable populations would benefit from policies that focus on alternative financial mechanisms to help stabilize income-insecure individuals in the short-term.

Objective.To investigate whether tumor necrosis factor inhibitor (TNFi) combination therapy with conventional synthetic disease-modifying antirheumatic drugs (csDMARD) is more effective for psoriatic arthritis (PsA) and/or improves TNFi drug survival compared to TNFi monotherapy.Methods.Five PsA biologics cohorts were investigated between 2000 and 2015: the ATTRA registry (Czech Republic); the Swiss Clinical Quality Management PsA registry; the Hellenic Registry of Biologics Therapies (Greece); the University of Bari PsA biologics database (Italy); and the Bath PsA cohort (UK). Drug persistence was analyzed using Kaplan-Meier and equality of survival using log-rank tests. Comparative effectiveness was investigated using logistic regression with propensity scores. Separate analyses were performed on (1) the combined Italian/Swiss cohorts for change in rate of Disease Activity Score in 28 joints (DAS28); and (2) the combined Italian, Swiss, and Bath cohorts for change in rate of Health Assessment Questionnaire (HAQ).Results.In total, 2294 patients were eligible for the drug survival analysis. In the Swiss (P = 0.002), Greek (P = 0.021), and Bath (P = 0.014) databases, patients starting TNFi in combination with methotrexate had longer drug survival compared to monotherapy, while in Italy the monotherapy group persisted longer (P = 0.030). In eligible patients from the combined Italian/Swiss dataset (n = 1056), there was no significant difference between treatment arms in rate of change of DAS28. Similarly, when also including the Bath cohort (n = 1205), there was no significant difference in rate of change of HAQ.Conclusion.Combination therapy of a TNFi with a csDMARD does not appear to affect improvement of disease activity or HAQ versus TNFi monotherapy, but it may improve TNFi drug survival.

Objectives In order to address the reliability of commercial assays to identify myositis-specific and -associated autoantibodies, we aimed to compare the results of two commercial immunoassays with the results obtained by protein immunoprecipitation. Methods Autoantibody status was determined using radio-labelled protein immunoprecipitation for patients referred to our laboratory for myositis autoantibody characterization. For each autoantibody of interest, the sera from 25 different patients were analysed by line blot (Euroline Myositis Antigen Profile 4, EuroImmun, Lübeck, Germany) and dot blot (D-Tek BlueDiver, Diagnostic Technology, Belrose, NSW, Australia). Sera from 134 adult healthy controls were analysed. Results Overall commercial assays performed reasonably well, with high agreement (Cohen’s κ >0.8). Notable exceptions were the detection of rarer anti-synthetases with κ Conclusion The assays analysed do not perform well for all myositis-specific and -associated autoantibodies and overall false positives are relatively common. It is crucial that clinicians are aware of the limitations of the methods used by their local laboratory. Results must be interpreted within the clinical context and immunoprecipitation should still be considered in selected cases, such as apparently autoantibody-negative patients where anti-synthetase syndrome is suspected.

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Anti-synthetase syndrome (ASSD) is a heterogeneous autoimmune disease characterised by multi-system involvement with a wide variety of manifestations. Validated classification criteria are necessary to improve recognition and prevent misclassification, especially given the lack of reliable and standardised autoantibody testing. We systematically reviewed the literature to analyse proposed ASSD criteria, characteristics, and diagnostic performance. Methods We searched PubMed and Embase databases (01/01/1984 to 06/11/2018) and the ACR and EULAR meeting abstracts (2017-2018). Sensitivities, specificities, positive, negative likelihood ratios and risk of bias were calculated for ASSD criteria and key variables reported in the literature. We performed meta-analysis when appropriate. Results We retrieved 4,358 studies. We found 85 proposed ASSD criteria from a total of 82 studies. All but one study included anti-synthetase autoantibody (ARS) positivity in the ASSD criteria. Most studies required only one ASSD feature plus anti-ARS to define ASSD (n=64, 78%), whereas 16 studies required more than one ASSD variable plus anti-ARS. The only criteria not including anti-ARS positivity required 5 ASSD clinical features. We found limited data and wide variability in the diagnostic performance of each variable and definition proposed in the literature. Given these limitations we only meta-analysed the performance of individual muscle biopsy and clinical variables in diagnosing ASSD, which performed poorly. Conclusion The current ASSD criteria include a variety of serological, clinical, and histological features with wide variability amongst proposed definitions and the performance of these definitions has not been tested. This systematic literature review suggests the need for additional data and consensus-driven classification criteria for ASSD.

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

Background: Psoriatic nail dystrophy is infrequently assessed in routine care and observational cohorts due to the lack of a feasible validated outcome measure. Objective: To assess the measurement properties of the “Severity of NAil Psoriasis Score” (SNAPS) in PsA. Methods: Nail photography was performed on prospectively recruited patients at baseline and 6 months. The modified Nail Psoriasis Severity Index (mNAPSI) and Physician Nail Visual Acuity Scale (PhNVAS) were comparator instruments for construct validity. Reliability and feasibility were assessed using intra-class correlations (ICCs) and timed scoring. Responsiveness was assessed by correlating the changes in SNAPS, mNAPSI and PhNVAS. Retrospective data from the Bath PsA database was further utilized to assess responsiveness. Results: 21 patients participated in the prospective validation at baseline. Inter- and intra-rater reliability of SNAPS were 0.94 and 0.93-0.96 (p ≤ 0.005). Mean times required to score SNAPS and mNAPSI were 59 and 136 seconds. There were strong correlations between SNAPS and mNAPSI (r = 0.95, p < 0.001) and PhNVAS (r = 0.77, p < 0.001) at baseline. There was a significant reduction in the mNAPSI and SNAPS (p < 0.005) at 6 months and a strong correlation between the change in SNAPS and mNAPSI (rho = 0.838, p < 0.001). Historical data from 57 patients commenced on Etanercept were evaluated. Mean SNAPS reduced from 3.6 to 2.0 at 3 months and 1.2 at 6 months (p < 0.05). Change in SNAPS correlated with changes in Psoriasis Area Severity Index and Dermatology Quality of Life at 3 and 6 months (r≥0.510; p ≤ 0.003). Conclusion: SNAPS is a feasible, reliable and responsive outcome instrument for psoriatic nail dystrophy.

Objective The current classification criteria for idiopathic inflammatory myopathy (IIM) retain PM as a major disease subgroup. However, evolution in the understanding of IIM has suggested that many of these patients could be better described as having an alternative diagnosis. In the present study, we apply the latest understanding of IIM subtyping to retrospectively review PM diagnoses in a large cohort of IIM patients. Methods Within a previously reported cohort of 255 patients from a UK tertiary myositis clinic, 37 patients classified as PM according to both the EULAR/ACR IIM criteria and expert opinion were identified. Clinical data and complementary tests were reviewed, and consensus decisions regarding final classification were reached in each case. Results Nine (9/37, 24.3%) patients remained classified as PM, 3.5% (9/255) of the original cohort; these PM patients were seronegative for myositis antibodies, responsive to immunosuppression, and in 4/7 (57.1%) patients where muscle biopsy was performed had HLA-1 upregulation and endomysial inflammatory infiltrates. Immune-mediated necrotizing myopathy (5/37, 13.5%) and connective tissue disease overlap myositis (7/37, 19%) were the main alternative diagnoses. The remaining patients were diagnosed as: unspecified myopathy (6/37, 16%), dermatomyositis (2/37, 5%), cancer-associated myopathy (3/37, 8.1%), and non-inflammatory myopathy (1/37, 3%, myofibrillar myopathy). Four patients (4/37, 10%) had insufficient data available to confidently reclassify. Conclusion Our study confirms that PM can now be considered a rare IIM subgroup. A thorough examination, complete myositis autoantibody panel, and careful interpretation of the biopsy results is recommended to confirm the correct IIM sub-type.

Objective To test the addition of pain and fatigue to the Composite Psoriatic Arthritis Disease Activity (CPDAI) and the Group for Research and Assessment of Psoriasis and PsA (GRAPPA) Composite Exercise (GRACE) composite measures of psoriatic arthritis (PsA). Methods Clinical and patient-reported outcome measures were assessed in patients with PsA at 3 consecutive follow-up visits over 6 months in a UK multicenter observational study. A pain visual analog scale and Functional Assessment of Chronic Illness Therapy Fatigue scale were added as modifications to the CPDAI and GRACE composite measures. Original and modified versions were tested against the PsA Disease Activity Score (PASDAS) and the Disease Activity Index for PsA (DAPSA). Discrimination between disease states and responsiveness were tested with t-scores, standardized response means (SRMs), and effect sizes. Data were presented to members at the 2020 annual meeting who then voted on the GRAPPArecommended composite and treatment targets for clinical trials. Results One hundred forty-one patients were recruited with a mean PsA disease duration of 6.1 years (range 0–41 yrs). The SRMs for the GRACE and modified GRACE (mGRACE) were 0.67 and 0.64, respectively, and 0.54 and 0.46, respectively, for the CPDAI and modified CPDAI (mCPDAI). The t-scores for the GRACE and mGRACE were unchanged at 7.8 for both, and 6.8 and 7.0 for the CPDAI and mCPDAI, respectively. The PASDAS demonstrated the best responsiveness (SRM 0.84) and discrimination (t-scores 8.3). Most members (82%) agreed the composites should not be modified and 77% voted for the PASDAS as the GRAPPA-recommended composite for clinical trials, with 90% minimal disease activity (MDA) as the target. Conclusion Modifying the CPDAI and GRACE with the addition of pain and fatigue does not enhance responsiveness nor the measures’ ability to detect disease status in terms of requiring treatment escalation. GRAPPA members voted for the PASDAS as the composite measure in clinical trials and MDA as the target.