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Background:Oral glucocorticoids (GC) are frequently prescribed to patients with rheumatoid arthritis (RA), however GC use is associated with a number of potential side effects. Hypertension is cited as a possible side effect, but few studies have specifically investigated GC-associated hypertension in patients with RA with conflicting results.Objectives:The aim of this study was to determine whether GCs were associated with an increased risk of incident hypertension in a cohort of patients with RA.Methods:A retrospective cohort of patients with incident RA and no hypertension at RA diagnosis were identified from UK primary care electronic health records (Clinical Practice Research Datalink). GC prescriptions were used to determine time-varying GC use and dose, categorised as: no use, >0–4.9 mg/day, 5–7.4 mg/day, 7.5–14.9 mg/day, ≥15mg/day. A 3-month risk attribution model was used where patients continued to remain at risk for 3 months after the end of prescriptions. Hypertension was identified if a patient had either: 1) 2 consecutive systolic blood pressure (BP) measurements >140mmHg within a year, 2) 2 consecutive diastolic BP measurements >90mmHg within a year or 3) antihypertensive prescriptions on at least two occasions and a Read code for hypertension. Unadjusted and adjusted Cox proportional hazards (PH) regression models were fitted to determine if there was an association between GC use and hypertension. Models were adjusted for baseline age, gender, baseline body mass index, baseline ever smoking, time-varying synthetic disease-modifying anti-rheumatic drug use, time-varying non-steroidal anti-inflammatory drug use and baseline Charlson comorbidity index.Results:There were 17,760 patients with incident RA and no hypertension. The cohort had a mean age of 56.3 ± 12.7 years and were predominantly female (68%). 7,421 (42%) were prescribed GCs during follow-up. There were 6,243 cases of incident hypertension over 97547 person years (pyrs) of follow-up, giving an incident rate of 64.1 per 1000 pyrs. Of those 1321 cases were in those exposed to GCs and 4922 were in those unexposed, giving incident rates of 87.6 per 1000 pyrs and 59.7 per 1000 pyrs, respectively. The adjusted Cox PH model indicated that recent GC use was associated with a 17% increased hazard of hypertension (hazard ratio: 1.17 (95% CI 1.10 to 1.24)). When categorised by dose, the adjusted model indicated only doses above 7.5mg were significantly associated with hypertension (Table 1).Table 1.Unadjusted and adjusted Cox proportional hazards regression model resultsUnadjustedHR (95% CI)Age and gender adjustedHR (95% CI)Fully adjusted* HR (95% CI)Recent GC use1.44(1.35 to 1.53)1.23(1.16 to 1.31)1.17(1.10 to 1.24)Recent GC doseNo GC useReferenceReferenceReference>0 – 4.9mg1.35(1.21 to 1.53)1.13(1.01 to 1.28)1.10(0.98 to 1.24)5mg – 7.4mg1.40(1.22 to 1.60)1.11(0.97 to 1.27)1.07(0.93 to 1.23)7.5mg – 14.9mg1.44(1.33 to 1.57)1.26(1.16 to 1.38)1.18(1.08 to 1.29)15mg and over1.60(1.40 to 1.84)1.45(1.27 to 1.66)1.36(1.18 to 1.56)* Adjusted for: Baseline age, gender, baseline body mass index, baseline ever smoking, synthetic disease-modifying anti-rheumatic drug use (time-varying), non-steroidal anti-inflammatory drug use (time-varying) and baseline Charlson comorbidity index.Conclusion:In this large cohort of patients with RA and without hypertension, recent GC use was associated with incident hypertension. In particular doses ≥7.5mg were associated with hypertension while the association with lower doses was inconclusive. Clinicians need to consider cardiovascular risk when prescribing GCs and ensure BP is regularly monitored.Disclosure of Interests:Ruth E Costello: None declared, Belay Birlie Yimer: None declared, Meghna Jani Speakers bureau: Grifols, William Dixon Consultant of: Bayer and Google

The rise in opioid prescriptions and mortality in the US1 has shone a light on similar concerns in the UK. Opioid prescriptions for non-cancer pain rose by about 60% in the UK from 2000 to 2010.2 With more use comes a larger burden of side effects, dependency, and divergence. The number of deaths related to opioid misuse in England and Wales …

The treatment of rheumatoid arthritis (RA) has undergone considerable changes over the last 15–20 years. With an expansion in the armamentarium of therapies available for RA comes a wider choice in selecting the best treatment in terms of comparative safety in the presence of comorbidities. Clinicians frequently encounter patients with RA-associated interstitial lung disease with uncontrolled joint disease and have to make decisions about the safest treatments in this context with the eventual goal of joint remission. In this chapter, available evidence is reviewed on the comparative pulmonary safety of non-biologic disease-modifying antirheumatic drugs (nbDMARDs), biologic DMARDs, biosimilars and targeted synthetic DMARDs in RA-ILD. In addition, the potential role for additional immunosuppression in RA-ILD is reviewed as well as overarching recommendations proposed for patient assessment to guide treatment decisions and management.

In an era of rapidly expanding digital technologies and social media (SM), considerable transformations in the delivery of healthcare are taking place. SM channels such as Facebook and Twitter represent a generation of online platforms that foster user-generated content, social interaction and real-time collaboration.1 In this letter, we review the advantages and disadvantages of engaging with Twitter within the rheumatology field. The ease of access to a wide range of SM platforms provides a dynamic medium for professional interaction. Twitter is gaining increasing attention by healthcare professionals as a platform for information sharing and professional networking, learning and communication. Twitter journal clubs (@RheumJC2 and @EULAR_JC3) are some examples of novel educational uses of Twitter. Despite the many positive applications of Twitter, potential hazards cannot be underestimated. The restricted character count of a tweet (140 characters) represents an important limitation, posing a …

TNF-α inhibitor (TNFi) therapies have transformed the treatment of several rheumatic musculoskeletal diseases. However, the majority of TNFi’s are immunogenic and consequent anti-drug antibodies formation can impact on both treatment efficacy and safety. Several controversies exist in the area of immunogenicity of TNFis and drug safety. While anti-drug antibodies to TNFis have been described in association with infusion reactions; serious adverse events (AEs) such as thromboembolic events, lupus-like syndrome, paradoxical AEs, for example, vasculitis-like events and other autoimmune manifestations have also been reported. The expansion of the biologic armamentarium, new treatment strategies such as introduction/switching to biosimilars and cost-saving approaches such as TNFi tapering, may all have a potential impact on immunogenicity and clinical sequelae. In this review we evaluate how evolution of biologics relates to drug safety and immunogenicity, appraise relevant evidence from trials, spontaneous pharmacovigilance and observational studies and outline the areas of uncertainty that still exist.

International audience; Recent insights in rheumatoid arthritis (RA) necessitated updating the European League Against Rheumatism (EULAR) RA management recommendations. A large international Task Force based decisions on evidence from 3 systematic literature reviews, developing 4 overarching principles and 12 recommendations (vs 3 and 14, respectively, in 2013). The recommendations address conventional synthetic (cs) disease-modifying antirheumatic drugs (DMARDs) (methotrexate (MTX), leflunomide, sulfasalazine); glucocorticoids (GC); biological (b) DMARDs (tumour necrosis factor (TNF)-inhibitors (adalimumab, certolizumab pegol, etanercept, golimumab, infliximab), abatacept, rituximab, tocilizumab, clazakizumab, sarilumab and sirukumab and biosimilar (bs) DMARDs) and targeted synthetic (ts) DMARDs (Janus kinase (Jak) inhibitors tofacitinib, baricitinib). Monotherapy, combination therapy, treatment strategies (treat-to-target) and the targets of sustained clinical remission (as defined by the American College of Rheumatology-(ACR)-EULAR Boolean or index criteria) or low disease activity are discussed. Cost aspects were taken into consideration. As first strategy, the Task Force recommends MTX (rapid escalation to 25 mg/week) plus short-term GC, aiming at >50% improvement within 3 and target attainment within 6 months. If this fails stratification is recommended. Without unfavourable prognostic markers, switching to-or adding-another csDMARDs (plus short-term GC) is suggested. In the presence of unfavourable prognostic markers (autoantibodies, high disease activity, early erosions, failure of 2 csDMARDs), any bDMARD (current practice) or Jak-inhibitor should be added to the csDMARD. If this fails, any other bDMARD or tsDMARD is recommended. If a patient is in sustained remission, bDMARDs can be tapered. For each recommendation, levels of evidence and Task Force agreement are provided, both mostly very high. These recommendations intend informing rheumatologists, patients, national rheumatology societies, hospital officials, social security agencies and regulators about EULAR's most recent consensus on the management of RA, aimed at attaining best outcomes with current therapies.

Background Up to 40% of patients with inflammatory arthritis on TNF-α inhibitor (TNFi) treatment fail to respond either due to primary inefficacy or loss of response. One explanation is immunogenicity leading to the development of anti-drug antibodies (ADAb) and subsequent low drug levels. Few data exist on whether such pharmacological tests correlate with treatment response in psoriatic arthritis (PsA). The clinical utility of whether such tests should be incorporated into practice is in question. Objectives To identify (i) whether the presence of ADAbs/drug levels predict treatment response and disability in TNFi-treated PsA patients (ii) the factors associated with drug levels (iii) a drug level threshold for optimal therapeutic response. Methods 75 patients were available from the Outcomes of Treatment in PsA Study Syndicate (OUTPASS) [n=49 adalimumab; n=26 etanercept], a national UK prospective observational cohort. Serum samples were collected at 3, 6 and 12 months following initiation of TNFi therapy. ADAbs were measured using radioimmunoassay (RIA) and random (non-trough) drug levels using ELISA assays at 3, 6 and 12 months. Disease activity (DAS28) scores were measured at each visit. Patient self-reported adherence to TNFi was measured at each time-point. Generalised estimating equation (GEE) was used to test the association between ADAbs and drug levels, both biomarkers and treatment response [as assessed by change in DAS28 score between pre-treatment and 12 months post-treatment (ΔDAS28)], Health assessment Questionnaire (HAQ) and the association between longitudinal/baseline factors with drug levels. Results 264 serial samples were suitable for pharmacological testing (n=174 adalimumab; n=90 etanercept). Mean age was 51±12 years; 61% were female; median BMI 28.9 (IQR 26.0–34.9). 20% (n=10/49) of adalimumab-treated patients were positive for ADAbs, but none were detected in etanercept-treated patients. There was no significant association between etanercept drug levels and ΔDAS over 12 months [β= -0.039 (95% CI -0.31, 0.23), p=0.77]. Using GEE, adalimumab drug levels were significantly associated with ΔDAS28 over 12 months [β=0.055 (95% CI: 0.011, 0.099) p=0.014] and inversely with HAQ scores over 12 months [β= -0.022 (95% CI: -0.043, -0.00063]. ΔDAS28 was not independently associated with ADAb level [β=-0.0015 (95% CI: -0.0031, 0.000047), p=0.057]. Adalimumab concentrations between 4.5–8.5 mg/L were associated with an optimal treatment response at 6 months using concentration-effect curves. Factors that were significantly associated with adalimumab drug levels were ADAb level [β=-0.0073 (95% CI: -0.0014, 0.18), p Conclusions TNFi drug-level testing in adalimumab-initiated PsA patients may be useful in determining treatment response and disability over 12 months; interestingly, both the presence of ADAbs and BMI were inversely associated with drug levels. Identification of a drug level threshold for optimal response may help tailor adalimumab therapy for PsA patients in the future. Acknowledgements This work was funded from a grant awarded by the National Institute of Health and Research, Manchester Musculoskeletal BRU to MJ, AB. Disclosure of Interest M. Jani Grant/research support from: Abbvie, UCB, Pfizer, H. Chinoy Grant/research support from: Novartis, Abbvie, Consultant for: Eli-Lilly and Novartis, Speakers bureau: UCB, A. Barton Grant/research support from: Eli-Lilly, Speakers bureau: Roche Chugai and Pfizer

Background Opioid use for non-cancer pain has increased considerably over the last 30 years. The U.S. Food and Drug Administration announced several boxed warnings in 2016 to highlight serious opioid-related risks (1) in an effort to reduce fatal overdoses, 80% of which are unintentional (2). The most serious opioid related adverse event is respiratory depression (RD), which can be potentially fatal. There are few data on the incidence of RD in opioids users for non-malignant pain and no comparative data between drugs. Objectives To assess the comparative risk of RD in new users of opioids for non-malignant pain using routinely collected electronic patient records (EPR). Methods Opioid users from Salford hospital EPR were identified between 2014–2016. Patients with prior malignancy were excluded on the basis of ICD-10 codes and health issues. Those with prior history of opioid use were excluded using keyword searches within the medicines reconciliation document. The primary analysis was on drug + 1 day lag window, unless patient switched to another opioid. Exposure was categorised as opioid monotherapy by drug or combination of opioids (so that RD events could be assigned to a single exposure category). Electronic National Early Warning Scores, used to regularly monitor physiological parameters during inpatient visits, were used to classify RD. An RD event was defined as any one of the following: respiratory rate (RR) ≤8/min, RR ≤10/min and oxygen saturations Results 8007 opioid users were included in the study, 3,976 female (50%) and a mean age (SD) of 53 (21) years. There were 255 RD events observed on treatment, 87 with severe respiratory depression (RR Conclusions Fentanyl, oxycodone, morphine monotherapy have a significantly higher risk of RD than codeine, but these are not significantly different from each other. Combination opioids confer the highest risk of RD, compared to both codeine and morphine. The strengths of this study include capture of real time physiological parameters to define RD and dispensed medication use (rather than prescribed) to define exposure. References FDA Drug Safety Communication: March 2016. http://www.fda.gov/Drugs/DrugSafety/ucm489676.htm.2016. CDC. Wide-ranging OnLine Data for Epidemiologic Research (WONDER); 2014. http://wonder. cdc.gov/mortSQL.html. Disclosure of Interest None declared

ObjectivesTo explore perceptions, barriers and patterns of social media (SM) use among rheumatology fellows and basic scientists.MethodsAn online survey was disseminated via Twitter, Facebook and by email to members of the Emerging European League Against Rheumatism Network. Questions focused on general demographics, frequency and types of SM use, reasons and barriers to SM use.ResultsOf 233 respondents (47 countries), 72% were aged 30–39 years, 66% female. 83% were active users of at least one SM platform and 71% were using SM professionally. The majority used SM for communicating with friends/colleagues (79%), news updates (76%), entertainment (69%), clinical (50%) and research (48%) updates. Facebook was the dominant platform used (91%). SM was reported to be used for information (81%); for expanding professional networks (76%); new resources (59%); learning new skills (47%) and establishing a professional online presence (46%). 30% of non-SM users justified not using SM due to lack of knowledge.ConclusionsThere was a substantial use of SM by rheumatologists and basic scientists for social and professional reasons. The survey highlights a need for providing learning resources and increasing awareness of the use of SM. This could enhance communication, participation and collaborative work, enabling its more widespread use in a professional manner.

Lung disease is one of the most common causes of extra-articular morbidity and mortality in patients with rheumatoid arthritis (RA). Development of pulmonary manifestations may be due to the systemic disease itself; to serious respiratory adverse events such as pneumonitis and infections secondary to therapy; or to lifestyle habits such as smoking. Rheumatologists often need to make important treatment decisions and plan future care in RA patients with respiratory comorbidities, despite the absence of clear evidence or consensus. In this review we evaluate the clinical assessment and management of RA-associated interstitial lung disease, bronchiectasis, serious (including opportunistic) infection, and smoking-related diseases. We summarize the international recommendations for the management of such conditions where available, refer to published best practice on the basis of scientific literature, and propose practical management suggestions to aid informed decision-making.

The management of RA, SpA, psoriasis and inflammatory bowel disease has significantly improved over the last decade with the addition of tumour necrosis factor inhibitors (anti-TNFs) to the therapeutic armamentarium. Immunogenicity in response to monoclonal antibody therapies (anti-drug antibodies) may give rise to low serum drug levels, loss of therapeutic response, poor drug survival and/or adverse events such as infusion reactions. To combat these, the use of concomitant MTX may attenuate the frequency of anti-drug antibodies in RA, SpA and Crohn's disease. Although a similar effect to methotrexate has been observed with AZA usage in the management of Crohn's disease, there is insufficient evidence to suggest that other DMARDs impact immunogenicity. In this article we review the evidence to date on the effect of immunomodulatory therapy when co-administered with anti-TNFs. We also discuss whether such a strategy should be employed in SpA and psoriasis, and if optimization of the MTX dose could improve biologic drug survival and thereby benefit disease management.

The last decade has been an era of exciting and innovative therapeutic targets in the treatment of moderate-to-severe rheumatoid arthritis. One such treatment that acts by disrupting T-cell activation is abatacept, which is currently used in patients who have had an inadequate clinical response to traditional disease-modifying drugs or anti-TNF therapies. As newer therapies emerge, issues that need addressing include: long-term drug tolerance, adverse events, sustained clinical response, prevention of progression in structural damage and retention rates. In this article we discuss a recently published paper by Kremer et al. that reported 3-year data on safety, efficacy and radiographic progression in patients enrolled in a clinical trial of abatacept, as well as the advantages and limitations of long-term extension studies.

Idiopathic inflammatory myopathies (IIMs) may present as a primary autoimmune disorder, or overlap with other autoimmune/connective tissue diseases. The aetiology of IIM likely includes interactions between genetic and environmental factors. Several genetic variants common to multiple autoimmune disorders have been identified in recent genome-wide association studies (GWAS). A Myositis Genetics Consortium dermatomyositis (DM) GWAS also suggests genetic overlap with other autoimmune disorders.1 We sought to extend these findings to identify novel genetic risk factors in a large cohort of adult/juvenile patients with DM and polymyositis (PM), by genotyping immune-related single nucleotide polymorphisms (SNPs) not captured through the DM GWAS.1 SNPs significantly associated (p

In recent years, social media websites have been suggested as a novel, vast source of data which may be useful for deriving drug safety information. Despite this, there are few published reports of drug safety profiles derived in this way. The aims of this study were to detect and quantify glucocorticoid-related adverse events using a computerised system for automated detection of suspected adverse drug reactions (ADR) from narrative text in Twitter, and to compare the frequency of specific ADR mentions within Twitter to the frequency and patterns of spontaneous ADR reporting to a national drug regulatory body. Of 159,297 tweets mentioning either prednisolone or prednisone between 1

This study evaluated the first year's experience of a large interventional centre in the UK after a primary percutaneous coronary intervention (PCI) programme that runs 24 hours a day and seven days a week was started. Workload, patient outcome, length of stay, and effect on the remainder of the interventional service were analysed. The primary PCI service for a mainly urban population of 800,000 was started in April 2005. All relevant characteristics, details of procedures, outcome, and other data on quality of care were collected and entered prospectively onto a computerised database. Data were analysed with SPSS (version 13.0). Over a 12-month period, 305 patients were diagnosed with ST elevation myocardial infarction (STEMI), of whom 259 (85%) were accepted for primary PCI. Median door-to-balloon time was 98 minutes, which decreased from 106 minutes in the first six months to 93 minutes in the second six months (p < 0.005). In-hospital mortality was 4.5% and 30-day mortality was 4.9%. Median length of stay was three days, which was reduced from the six days previously reported after thrombolysis. Waiting times for other acute and elective PCI procedures did not increase after initiation of the primary PCI programme. Primary PCI can be delivered successfully in a setting in the UK with low mortality and reduced length of stay and without a negative impact on other interventional services.

Objectives: To identify and quantify resource required and associated costs for implementing TNF-α inhibitor (TNFi) drug level and anti-drug antibody (ADAb) tests in UK rheumatology practice.Methods: A microcosting study, assuming the UK National Health Service perspective, identified the direct medical costs associated with providing TNFi drug level and ADAb testing in clinical practice. Resource use and costs per patient were identified via four stages: identification of a patient pathway with resource implications; estimation of the resources required; identification of the cost per unit of resource (2015 prices); and calculation of the total costs per patient. Univariate and multiway sensitivity analyses were performed using the variation in resource use and unit costs.Results: Total costs for TNFi drug level and concurrent ADAb testing, assessed using ELISAs on trough serum levels, were £152.52/patient (range: £147.68–159.24) if 40 patient samples were tested simultaneously. For the base–case analysis, the pre-testing phase incurred the highest costs, which included booking an additional appointment to acquire trough blood samples. The additional appointment was the key driver of costs per patient (67% of the total cost), and labour accounted for 10% and consumables 23% of the total costs. Performing ELISAs once per patient (rather than in duplicate) reduced the total costs to £133.78/patient.Conclusion: This microcosting study is the first assessing the cost of TNFi drug level and ADAb testing. The results could be used in subsequent cost-effectiveness analyses of TNFi pharmacological tests to target treatments and inform future policy recommendations.

Objective. To determine the concordance between RIA and bridging ELISA at detecting anti-drug antibodies (ADAbs) in the context of random adalimumab levels and investigate the additional clinical utility of detecting ADAbs in RA patients who test ADAb positive by RIA and negative by ELISA. Methods. ADAb levels were determined using RIA and bridging ELISA in 63 adalimumab-treated RA patients (159 samples). Immunogenicity concordance was determined using receiver operating characteristic curves. To determine the additional clinical value provided by a positive RIA in the presence of negative ELISA, association between treatment response (ΔDAS28), adalimumab drug levels and ADAbs was evaluated longitudinally using generalized estimating equation. Results. Of the 60 RIA+ samples (n = 31 patients), 19 (n = 10 patients) were also ELISA+, corresponding to 31.7% of samples. Area under the curve for detecting ADAbs using ELISA (compared with RIA) using receiver operating characteristic curves was 0.65 (95% CI: 0.59, 0.71); this increased to 0.91 (95% CI: 0.81, 0.99) if ADAbs were ⩾100 AU/ml using RIA. In RIA+/ELISA− patients, adalimumab levels were associated with ΔDAS28 over 12 months [regression coefficient: 0.098 (95% CI: 0.043, 0.15), P

Up to 40% of patients with rheumatoid arthritis treated with anti-tumour necrosis factor (TNF) drugs do not respond because of primary inefficacy or loss of response. Although one explanation is that immunogenicity leads to the development of anti-drug antibodies and low drug concentrations, the clinical usefulness of pharmacological monitoring is debated. Our aim was to assess whether the presence of anti-drug antibodies and non-trough drug concentrations could predict treatment response in patients with rheumatoid arthritis treated with anti-TNF drugs.331 patients were selected from a multicentre prospective cohort (160 treated with adalimumab, 171 etanercept). Serum samples were collected at 3, 6, and 12 months after treatment initiation. Anti-drug antibodies were measured with RIA, drug concentrations with ELISAs, and Disease Activity Score in 28 joints (DAS28) at each timepoint. Linear and logistic regression, generalised estimating equation (GEE), and receiver operating characteristic curves were used to test the association and predictive value of anti-drug antibodies and non-trough drug concentrations on treatment response (ΔDAS28).835 serial samples were tested (414 adalimumab, 421 etanercept). Anti-adalimumab antibodies were detected in 31 (24·8%) of 125 patients who had completed 12 month follow-up and none of the etanercept patients. The presence of anti-drug antibodies was associated with lower adalimumab concentrations (Spearman r=-0·66, p=0·0041). At 3 months, anti-drug antibody formation and low adalimumab concentrations were significant predictors of poor treatment response at 12 months (area under curve [AUC] 0·68, 95% CI 0·54-0·81, and 0·66, 0·55-0·77, respectively; and both combined 0·71, 0·57-0·85). Adalimumab concentration was the most significant independent predictor of ΔDAS28 after adjustment for confounders (regression coefficient 0·12, 95% CI 0·06-0·18; p=0·003). High etanercept concentrations were associated with better treatment response (p=0·01), but low concentrations at 3 months were not a significant predictor of poor treatment response at 12 months (AUC 0·58, 95% CI 0·46-0·70). In the combined GEE model including adalimumab and etanercept, a body-mass index of 30 kg/m(2) or more was associated with low drug concentrations (regression coefficient 0·78, 95% CI 0·37-1·18; p0·0001).Pharmacological testing in anti-TNF initiated patients is clinically useful even in the absence of trough levels. At 3 months, presence of anti-drug antibodies and low adalimumab concentrations are a significant predictor for poor treatment response at 12 months. Strengths of this study include a large, prospective cohort and use of RIA to measure antibodies (less prone to drug interference). Although non-trough concentrations might have underestimated the frequency of antibodies, their presence still predicted response.MJ is a MRC Clinical Training Fellow supported by the North West England Medical Research Council Fellowship Scheme in Clinical Pharmacology and Therapeutics, which is funded by the UK Medical Research Council (grant number G1000417/94909), ICON, GlaxoSmithKline, AstraZeneca, and the Medical Evaluation Unit. Arthritis Research UK (grant ref 20385).

TNF-blocking agents, non-biological disease-modifying anti-rheumatic drugs (nbDMARDs) and non-steroidal anti-inflammatory drugs (NSAIDs) are commonly prescribed treatments in psoriatic arthritis. A large proportion of patients do not respond to these medications, although unfortunately clinically useful biomarkers that predict future response are currently lacking. Several candidate gene polymorphisms have been associated with responses to biologic therapies and nbDMARDs; however, replication and validation of these variants in large prospective psoriatic arthritis cohorts are required before translating these to clinical practice. In this review, we discuss the advances made in pharmacogenetics of treatment response in psoriatic arthritis to date, with focus on biologic therapies approved for use, nbDMARDs and NSAIDs, as well as outline emerging methodologies to obtain data that will help inform a future precision medicine approach in this condition.

Interstitial lung disease (ILD) is a common extra-articular manifestation associated with increased morbidity and mortality in patients with rheumatoid arthritis (RA). Early case reports of serious respiratory adverse events (SRAEs) following treatment with anti-TNF agents have led to concerns about biologic therapy in patients with RA-associated ILD (RA-ILD), and a tendency for biologic agents targeting factors other than TNF to be prescribed in such patients. At present, the appropriateness of such decisions is not clear. Given that the therapeutic goal for RA is remission, clinicians increasingly face the challenge of choosing the optimal biologic agent in patients with RA-ILD and uncontrolled joint disease. However, no evidence-based guidelines exist to guide physicians in deciding whether to commence biologic therapy in this setting, or in selecting which drug is most appropriate. Herein, we review the evidence for the comparative pulmonary safety of anti-TNF agents and non-TNF-targeting biologic agents in RA-ILD. In addition, we propose a framework for assessment of baseline disease severity to guide treatment decisions, and for monitoring during therapy. Because of substantial gaps in the available evidence, we also describe a research agenda aimed at obtaining data that will help inform future clinical practice.

Background The association between TNF inhibitors and vasculitis-like events, possibly secondary to induction of autoantibodies, has been well reported. However, the incidence, drug-specific differences, and associated factors have been poorly characterised. The aim of this study was to assess the drug-specific risk, and associated factors, of vasculitis-like events in patients with rheumatoid arthritis treated with TNF inhibitors and non-biologic disease modifying antirheumatic drugs (nbDMARDs). Methods This analysis included two cohorts from the British Society for Rheumatology Biologics Register for Rheumatoid Arthritis (BSRBR-RA) recruited from Oct 1, 2001, to May 31, 2015: patients starting first TNF inhibitors (adalimumab, etanercept, infliximab, certolizumab) and a comparison cohort receiving nbDMARDs. After identification of vasculitis-like events, additional information from hospital consultants was sought for verification. The risk of an event was compared between the two cohorts with Cox proportional hazard models, adjusted using propensity scores (inverse probability of treatment weighting). Findings There were 95 incident vasculitis-like events (14 in 3640 patients on nbDMARD, 81 in 12 745 patients starting first TNF inhibitors) with 20 365 and 52 428 patient-years of follow-up generating crude incidence rates of 7 per 10 000 and 16 per 10 000 person-years, respectively. After adjustment, the hazard ratio (HR) of vasculitis-like events in patients on TNF inhibitors versus nbDMARD was 1·3 (95% CI 0·4–4·0). Drug specific HRs were highest in patients on infliximab (HR 2·7, 95% CI 1·4–5·2) and etanercept (2·6, 1·4–4·8), but these associations were not significant after adjustment. Factors associated with vasculitis-like events included baseline disease activity (HR 1·4, 95% CI 1·2–1·7), rheumatoid factor positive status (1·8, 1·2–2·8), health assessment questionnaire score (1·7, 1·2–2·3), and sulfasalazine use (0·6, 0·3–0·9). Interpretation In one of the largest registers of patients receiving biological drugs, the absolute risk of vasculitis-like events was low, irrespective of whether patients received TNF inhibitors or nbDMARDs. There were no significant differences in risk between TNF inhibitors after adjustment. Higher baseline disease activity and seropositive status were associated with higher rates of vasculitis events, whereas baseline sulfasalazine use was associated with lower rates. To our knowledge, this is the first study to date to assess the risk of this outcome in a prospective, observational cohort. Funding Medical Research Council.

The outlook of chronic inflammatory conditions such as rheumatoid arthritis (RA), spondyloarthritis, psoriasis and inflammatory bowel disease has been revolutionised by the use of tumour necrosis factor inhibitors (TNFi). In the management of moderate to severe psoriatic arthritis (PsA), infliximab

Background The use of social media (SM) platforms and networks is fast expanding yet their impact especially within the professional world is often under-appreciated and has not been systematically evaluated. Objectives To perform an online survey on the use, perceptions and impact of SM within the rheumatology professional world and beyond. Methods A questionnaire prepared by rheumatologists from different countries within the EMEUNET group was designed to assess perceptions and the impact of SM among users and non-users. EMEUNET is a Europe-wide network of more than 1000 young rheumatologists addressing educational needs and promoting research interests. The survey covered a range of questions from basic demographic information to perceptions on the use and impact of SM in a professional or other. The survey was advertised via three main routes: Twitter, Facebook and by direct email to EMEUNET members. Results 233 anonymized responses were collected from 47 countries. The majority completed the survey via email (90%), the rest via Tw (6%) and FB (4%). 72% of responders were within the age group of 30-39 years. 66% were female; 51% were in a combined clinical/academic job setting. 83% were active users of at least one SM platform with a mean weekly use of 7 hrs, and 71% of those used SM in a work-related manner. The majority used SM for communicating with friends/colleagues (79%), news updates (76%), entertainment (69%), rheumatology clinical (50%) and research (48%) updates. Table 1 shows SM sites and the frequency of use. FB was the dominant SM platform with 91% using it although only 68% professionally, whereas LinkedIn was the dominant platform for professional-related communication. The latter included using SM as a source of information (81%); expanding professional networks (76%); new resources (59%); learning new skills (47%) and establishing a professional online presence (46%). Work-related SM users had a significantly increased use of SM (8 hrs weekly) of which 5 hours were work-related. The main obstacles for not using SM in a work-related manner were “lack of knowledge on how to do so” (44%) followed by “not suitable for individual needs” (30%). 9% were concerned regarding negative impact on their reputation. 68% felt that SM is a safe way of communicating with other people although of those not using SM 37% expressed concerns regarding its safety, exposure of private life and being a time-consuming process. 30% of non-SM users justified not using SM due to lack of knowledge; 26% considered SM unsuitable for their needs and 41% expressed no interest in SM. Conclusions The results highlight that use of SM within rheumatology professionals and basic scientists is considerable, for social but mostly professional reasons. SM provides a good source of information for educational purposes and potential for networking. he lack of knowledge on how to use SM in a work related manner highlights the need for providing resources necessary to enable more widespread use of SM. Despite concerns regarding the safety of SM and exposure of private life, the majority of respondents had a positive view towards SM. Acknowledgements We thank Dr David O9Reilly for his contribution. Disclosure of Interest None declared

Background Idiopathic inflammatory myopathies (IIM) may present as a primary disorder, or may overlap with connective tissue diseases such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) or systemic sclerosis. The aetiology of IIM is largely unknown, but is thought to include a combination of genetic and environmental factors. To generate ethnically homogeneous IIM cohorts of sufficient size given its rarity, one of the largest European IIM initiatives has enabled Europe wide ascertainment of cases with EUMYONET. Numerous genome-wide association studies (GWAS) have identified many genetic variants associated with autoimmune disorders, several common to multiple disorders. This is supported by our recent dermatomyositis (DM) GWAS, suggesting genetic overlap with other autoimmune disorders1. Objectives We sought to identify additional novel genetic risk factors in adult and juvenile polymyositis (PM) and DM (not previously identified by DM GWAS), shared with other autoimmune disorders. Methods SNPs significantly associated with SLE, RA, juvenile idiopathic arthritis, coeliac disease, Crohn's disease, ulcerative colitis, psoriasis, type 1 diabetes, multiple sclerosis or systemic sclerosis were identified from published Caucasian GWAS and from the national human genome research institute catalogue of published GWAS. 233 unique SNPs were identified ( p 5% missing genotype data were excluded, resulting in 1149 cases and 3572 controls. Outside the MHC region, a non-synonymous SNP rs2304256 in the TYK2 gene was identified reaching Bonferroni-corrected significance in IIM and DM (β= -0.21, p value=0.00027; β= -0.25, p value=0.00020 respectively). Two further SNPs within the BLK gene and 2335bp 5' of BLK were associated with DM (rs2618476, β=0.24, p value=0.00062; rs13277113, β=0.25 p value=0.00045 respectively) but not with PM, supporting the results of our DM GWAS. Conclusions We have identified TYK2 as a novel association for DM, suggesting genetic overlap of DM with other autoimmune disorders, and indicating genetic heterogeneity between PM and DM. TYK2 has been associated previously with SLE, type 1 diabetes and multiple sclerosis. Further associations of the BLK gene with DM, suggests a role of B cells in its development. References 1. Miller FW et al. Arthritis Rheum. 2013 Dec; 65(12):3239-3247 Acknowledgements Funding: Arthritis Research UK (grants 18474; 14518), Intramural Research Program of the NIH, Wellcome Trust (076113; 085860). We thank all other members of the EUMYONET and Myositis Genetics Consortium (MYOGEN). Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.2877

Background The introduction of tumour necrosis factor inhibitors represents a major advance in the treatment of rheumatoid arthritis (RA). Despite this, up to 40% of patients fail to respond- either due to primary inefficacy or loss of response. One explanation is immunogenicity leading to the development of anti-drug antibodies (ADAb) and low drug levels. Radioimmunoassay (RIA) is a sensitive method to detect ADAb and is less prone to drug interference vs . ELISA. The clinical utility of pharmacological monitoring in routine rheumatology practice is still debated with conflicting opinions. Objectives To evaluate whether ADAb formation and serum drug levels may predict future treatment response of anti-TNF initiated RA patients. Methods 331 patients were selected from the Biologics in RA Genetics and Genomics Study Syndicate prospective cohort [n=160 adalimumab (AD); n=171 etanercept (ETA)]. Serum samples were collected at 3, 6 and 12 months following initiation of therapy. ADAb were measured using RIA and drug levels using ELISA at 3, 6 and 12 months; the timing of blood samples was not consistently pre-dose. Disease activity (DAS28) scores were measured at each visit. Descriptive statistics, multiple linear regression and generalised estimating equation were used as appropriate. Results 835 serial samples were suitable for pharmacological testing (n=414 AD; n=421 ETA). Mean age: 56±13 years; 75% female; baseline DAS28 score 5.9±0.8; median BMI 27.5 (IQR 23.6-32.3). 85% were on a DMARD (56% MTX). ADAbs to AD were detected in 24.8% (31/125 patients at ≥1 time points by 12 months) and in none of the ETA patients. The presence of ADAbs were significantly associated with lower AD drug levels ( p 100AU p =0.0041; rs-0.66). At 3 months, ADAb formation and low drug levels were a significant predictor of poor ΔDAS28 at 6 and 12 months ( p 15μg/mL) were more likely to achieve a good EULAR response than patients with sub-therapeutic levels (

Background Adalimumab is a monoclonal antibody that targets the inflammatory cytokine tumour necrosis factor α and is effective in the treatment of rheumatoid arthritis. However efficacy of treatment with monoclonal antibodies can decrease over time after initial response. One explanation is the development of immunogenicity leading to the development of antibodies against the drug. Radioimmunoassay (RIA) is a sensitive method to detect anti-drug antibodies and has been previously reported to predict long-term efficacy. Our aim was to evaluate the occurrence of antibodies against adalimumab in a cohort of patients with rheumatoid arthritis followed longitudinally from therapy initiation and to test the association with treatment response. Methods In a prospective, multicentre study, serum samples from patients with rheumatoid arthritis treated with adalimumab were collected at 3, 6, and 12 months after treatment initiation. Antibodies to adalimumab were measured with RIA at each timepoint, with the disease activity score in 28 joints (DAS28) measured at baseline and each visit (high disease activity >5·1, moderate 3·2–5·1, low Findings 125 adalimumab-treated patients were available with clinical and biological samples at 3, 6, and 12 months for evaluation of immunogenicity. Mean age was 56 years (SD 12, 70% women). At treatment onset with adalimumab, most patients had never previously received a biological drug (112/125 [90%]), with 109 patients (87%) receiving concomitant disease modifying treatment. Mean DAS28 score at baseline was 5·8 (SD 0·3). Anti-adalimumab antibodies were detected in 31 patients (24%) at one or more timepoints after 12 months of treatment. By 12 months, patients who had developed anti-drug antibodies showed less improvement in disease activity than did patients without antibodies (mean change in DAS28=2·35, 95% CI 1·67–3·03 vs 3·15, 2·86–3·35; p=0·022). Interpretation Serum antibodies against adalimumab are associated with poorer response to treatment in rheumatoid arthritis. Anti-drug antibodies were detected using RIA, even though trough serum samples were not always obtained, reflecting a pragmatic clinical approach. Pharmacological monitoring to detect anti-drug antibodies in patients with rheumatoid arthritis on monoclonal antibody biological therapy might be useful in the prediction of long-term treatment response. Funding UK Medical Research Council [grant number G1000417/94909], ICON, GlaxoSmithKline, AstraZeneca, the Medical Evaluation Unit, Arthritis Research UK (grant number 20385).

Giant left atrium (GLA) is a well-described entity in association with rheumatic heart disease. However, mitral valve prolapse is an extremely unusual cause of GLA, especially without the compressive symptoms it can often accompany. We discuss a case of a 78-year-old lady with no prior history of rheumatic heart disease with these findings with the unusual presentation of accompanied unilateral breast oedema as a manifestation of heart failure. This case illustrates the investigations and treatment options for GLA and the need for prompt assessment as it increases the risk of sudden death; therefore, its presence warrants careful evaluation and surgical intervention when appropriate.

Background The idiopathic inflammatory myopathies (IIM) are autoimmune disorders characterised by acquired proximal muscle weakness, inflammatory cell infiltrates in muscle biopsies and myositis-specific or associated autoantibodies. Myositis may present as a primary disorder, or may overlap with other connective tissue diseases such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) or systemic sclerosis. The aetiology of IIM is largely unknown, but is thought to include a combination of both genetic and environmental factors. To generate ethnically homogeneous IIM cohorts of sufficient size, given the rarity of IIM, and to allow statistically meaningful research, one of the largest European IIM initiatives has enabled UK-wide ascertainment of cases with UK MYONET. Numerous recent genome-wide association studies (GWAS) have identified many genetic variants associated with autoimmune disorders, several of which are common to multiple disorders. Objectives To test the hypothesis that genetic risk factors associated with other autoimmune disorders also predispose to IIM. Methods SNPs significantly associated with SLE, RA, juvenile idiopathic arthritis, coeliac disease, Crohn’s disease, ulcerative colitis, psoriasis, type 1 diabetes, multiple sclerosis or systemic sclerosis were identified from published Caucasian GWAS and from the national human genome research institute (NHGRI) catalogue of published GWAS. 233 unique SNPs were identified (p -8 ), of which 99 had not been directly genotyped or captured through our MYOGEN GWAS. These SNPs were genotyped on the Sequenom platform in a sample of 391 UK Caucasian individuals with definite or probable adult or juvenile dermatomyositis or polymyositis. Genotype data was obtained from controls of European ancestry and imputation carried out for non-genotyped SNPs using HapMap Phase 3 and One Thousand Genomes data. Preliminary analysis was carried out using logistic regression in PLINK incorporating multi-dimensional scaling factors derived from the GWAS data as covariates to correct for population substructure. Results 391 individuals and 83 SNPs were successfully genotyped and passed quality control filtering criteria. Two SNPs within the HLA region were significantly associated with IIM (rs2040406 near HLA-DQA1 , p =6.21×10 -25 ; rs615672 near HLA-DRB1 , p =1.65×10 -9 ). Although no SNPs outside the HLA region achieved Bonferroni corrected significance levels for the number of SNPs tested, four SNPs previously associated with RA and SLE reached nominal significance (RA: rs13315591 in FAM107A , p =0.001; SLE: rs13385731 in RASGRP3 , p =0.001, rs5029939 in TNFAIP3 , p =0.004; rs2230926 in TNFAIP3 ; p =0.005). Conclusions The association of HLA SNPs confirms the autoimmune nature of IIM. The nominal association of four SNPs previously associated with SLE and RA suggests that IIM may share genetic risk factors with other autoimmune disorders. These results require confirmation in an independent replication sample. Disclosure of Interest None Declared

Background Hydroxy-methyl-glutaryl Coenzyme-A reductase (HMGCR) inhibitors or statins are a well-acknowledged cause of a spectrum of myopathic consequences including an asymptomatic increase of creatine kinase (CK), myalgias, myositis and rhabdomyolysis. A unique autoantibody with specificity against 200-kd and 100-kd proteins has been recently associated with statin induced myositis (1) based on identification of cases with features of necrotizing myopathy. The 100kd autoantigen has been identified as HMGCR (2). We sought to further characterize cases of clinically suspected statin-induced myositis using clinical, serological and pathological data. Objectives The aim was to characterize statin induced myositis patients in a clinical setting and test the utility of the newly identified anti-200/100 autoantibody. Methods Patients with a statin induced myositis were identified from a large tertiary myositis referral centre in Salford, UK. Case records of all patients were reviewed with selected patients’ blood samples tested for anti-200/100 autoantibody. Clinical features, concomitant medications, co-morbidities, immunology, electromyography (EMG), magnetic resonance imaging (MRI) and muscle biopsies for each patient were reviewed. Results 10 patients were identified with a clinical diagnosis of statin induced myositis. Mean age of diagnosis was 59 years (70% male). Median CK level detected at onset was 1,750 IU/litre (range 28-11,984). 9/10 patients were on a lipophilic statin (simvastatin/atorvastatin) with 1 patient on a hydrophilic statin (rosuvastatin); mean daily dose of 39mg/day prior to symptom onset. 5/10 patients were on a concomitant medication known to interact with a statin (amiodarone, proton pump inhibitors, high dose vitamin D). 3/10 patients were anti-nuclear-antibody positive (2 had low titres, 1/100; 1 positive 1/1000), whilst 2 patients were anti-Ro antibody positive. 6 patients demonstrated some evidence of myositis on MRI, of which 3 patients exhibited myopathic changes on EMG. 8 patients had evidence of myopathic muscle on biopsy, 2 patients with type II fibre atrophy. Of the 7 patients tested for anti-HMGCR by Western blotting using a recombinant source, 6 tested positive. 2 patients who tested strongly 200/100 positive required immunosuppression and had biopsy features of necrosis, phagocytosis and regeneration. 2 further 200/100 positive patients (1 strong and 1 weak positive) had occasional necrotic fibres with little regenerative activity on biopsy and did not require further treatment. The remaining 2 200/100 positive patients had no features of necrosis on biopsy, one of whom required immunosuppression without corticosteroids. Conclusions EMG and MRI were non-specific in identifying patients with a statin induced myositis, whilst CK levels varied significantly in this group. A strongly positive anti-200/100 antibody in combination with a necrotizing myopathy on muscle biopsy could be useful clinically to identify which patients have an autoimmune element to their disease, hence may potentially benefit from immunosuppression. References Christopher-Stine L et al. Arthritis Rheum 2010;62(9):2757–66. Mammen AL et al. Arthritis Rheum. 2011 Mar;63(3):713-21. Acknowledgements MJ is a MRC Clinical Training Fellow funded by the North West England Medical Research Council Fellowship Scheme in Clinical Pharmacology and Therapeutics. Disclosure of Interest None Declared

Background Treatment of psoriatic arthritis (PsA) has been revolutionized by the use of tumour necrosis factor inhibitors (TNF). The National Institute for Health and Clinical Excellence (NICE) is the health authority that provides clinical guidance for England and Wales. In the treatment of moderate-severe PsA, infliximab, adalimumab and etanercept were approved by 2007, followed by golimumab in 2011. NICE permits the use of sequential biologics in rheumatoid arthritis, however switching between anti-TNFs in PsA is not endorsed at present in the UK. Thus, PsA patients who fail on 1st line anti-TNF therapy due to inefficacy/adverse effects are left with no further therapeutic options. Limited data from open label studies and registries have confirmed the potential benefits of switching between anti-TNFs. Objectives Our aim was to assess compliance with current national guidance on a regional level in the UK, the outcome of patients who fail their 1st anti-TNF drug and obtain data in a clinical setting on the effectiveness of switching biologics in PsA. Methods A retrospective audit was conducted up to June 2012, to include all PsA patients on a current anti-TNFs in the North-West region of England. Each rheumatology department in the region was invited to participate. Data was collected locally by a designated site coordinator, then analysed centrally using Microsoft Excel 2011. Results Data on 548 patients was collected across 18 sites (mean age 48 years [range 20-80 years], 51% female). The mean time from diagnosis to commencing anti-TNF was 7.5 years, 28% were on biologic monotherapy and 72% were on a concomitant DMARD (84% of which methotrexate). The majority of patients were started on adalimumab 1st line (64%), followed by etanercept (34%), infliximab (2%) and golimumab (1%). At 12 weeks, 74% of patients had an adequate response. However, 24% of patients were not on their initial anti-TNF at the time of the audit (reasons included: 41% secondary inefficacy, 19% primary inefficacy, 26% intolerance, 4% pregnancy). 17% of all patients switched between anti-TNFs against national NICE guidance, with 3% switching between 3-4 biologics. Subsequent lines of biologics included anti-TNFs (including certolizumab pegol, n=1) but also rituximab (n=2), ustekinumab (n=1) and tocilizumab (n=1). 74% switched due to inefficacy, the remainder due to intolerance. In only 24% of switchers, local health authority permission was attained for funding; 4 patients had an individual funding request rejected. Of the switchers, 52% responded to 2nd line biologic therapy and 8% to 3rd line therapy; 19% were non-responders, 2% intolerant and 19% awaiting follow up to assess response to switching at the time of the audit. Conclusions Every centre in the region participated, most sites collecting information on all eligible patients representing an accurate reflection of current practice. There is regional variation regarding policy on switching anti-TNFs in PsA. The results signify a need for updating current national guidance and support the effectiveness of switching in PsA to allow more therapeutic alternatives for the most severely affected patients. Acknowledgements We would very much like to thank all the site co-ordinators in the North West region of England for collecting data: Dr B. Harrison, Dr S. Naz, Dr A. Madan, Dr D. Roy, Dr S. Wig, Sister J. Hawthorne, Dr P. Ho, Dr R. Muhamad, Sister J. Firth, Dr C. Sharp, Dr J. Little, Dr F. Wood, Dr M. Castelino, Dr E. Bruce, Dr L. Das, Dr F. Joseph, Dr L. Teh, Dr N. Thomas and Dr S Skeoch for co-ordinating the pilot regional audit in 2011. Disclosure of Interest None Declared

Background Idiopathic inflammatory myopathies (IIM) are a group of autoimmune disorders characterised by inflammation of muscles. They may present as a primary disorder or may overlap with other diseases such as rheumatoid arthritis, systemic lupus erythematosus, or systemic sclerosis. The cause of IIM is largely unknown, but is thought to include a combination of both genetic and environmental factors. Recent genome-wide association studies (GWAS) have identified many genetic variants associated with autoimmune disorders, several of which are common to multiple disorders. We tested the hypothesis that genetic risk factors associated with other autoimmune disorders also predispose to IIM. Methods Single-nucleotide polymorphisms (SNPs) significantly associated with systemic lupus erythematosus, rheumatoid arthritis, juvenile idiopathic arthritis, coeliac disease, inflammatory bowel disease, psoriasis, type 1 diabetes, multiple sclerosis, and systemic sclerosis were identified from published GWAS in white populations. 233 unique SNPs were identified (p −8 ), of which 99 had not been captured through our international myositis genetic collaboration GWAS. These SNPs were genotyped in a sample of 1043 European white individuals with adult or juvenile dermatomyositis or polymyositis who were compared with race-matched controls. Analysis was carried out with PLINK, followed by fixed-effects meta-analysis. Findings 1001 individuals and 83 SNPs passed quality control filtering criteria and were genotyped. Two SNPs within the HLA region were significantly associated with IIM (rs2040406 near HLA-DQA1 , p=2·23 × 10 −38 and rs615672 near HLA-DRB1 , p=6·07 × 10 −13 ). Two SNPs outside the HLA region achieved Bonferroni corrected significance levels (type 1 diabetes rs11171739, p=3·01 × 10 −7 and multiple sclerosis rs3135388, p=9·71 × 10 −7 ). SNPs associated with the genes FAM107A , TNFAIP3 , and BLK , previously linked with rheumatoid arthritis and systemic lupus erythematosus, were also associated with IIM. Interpretation The association of HLA SNPs confirms the autoimmune nature of IIM. The association of SNPs previously associated with type 1 diabetes, multiple sclerosis, systemic lupus erythematosus, and rheumatoid arthritis suggests that IIM may share genetic risk factors with other autoimmune disorders. Funding UK Medical Research Council and UK Myositis Support Group.