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Background Rising healthcare demand for people with rheumatic and musculoskeletal diseases in the UK is set to continue. Delivering sustainable outpatient rheumatology services, with a shift towards remote patient monitoring, virtual consultations, shared decision-making and supported self-management, is now a key NHS priority. Involving patients in outpatient rheumatology services transformation is considered a core prerequisite for success; a first step being to understand the perspectives of and preferences for care of patients with rheumatic and musculoskeletal diseases. Current evidence of perceived health service needs in people with inflammatory arthritis centres on rheumatoid arthritis; understanding about perceptions of people with axial spondyloarthritis (axSpA), in particular younger adults, is limited. The aim of this qualitative study was to explore in depth the experiences of, and preferences for, the delivery of NHS outpatient rheumatology services in adults diagnosed with AxSpA. Methods Five semi-structured focus groups were conducted between 2018 and 2019 with younger (age Results Thirty-three adults with AxSpA (18 men and 15 women) from diverse ethnic backgrounds and with a range of disease-related characteristics participated in the study. Thirteen participants were aged Conclusion Focus group members described a picture of inconsistent delivery of NHS rheumatology outpatient services in the UK. Preferences for care in adults with AxSpA largely align with proposals to transform NHS outpatient services and revolve around flexible delivery of patient-centred consultations, underpinned by shared decision-making and supported self-management. However, integrating these preferences into new models of care delivery to ensure optimal patient outcomes will require transformative action. These data can inform local and national developments to reconfigure outpatient services for people with AxSpA. Disclosures N. Wilson None. N. Kaiser None. J. Roose None. R. Martinez None. S. Steer None. H. Lempp None.

Background We live in an age where digital interactions are the norm. These may take the form of communication with friends and family, social media, contacting your bank or reading the daily news. Most of our rheumatology patients have smartphones or other digital platforms to access these. Healthcare, however, lags in adopting technology. Digital health solutions such as 'GP at hand' (Babylon) are still seen as disruptive market innovations. NHS improvement would like to reduce face-to-face activity by 10% through forms of digital enablement. We set out to develop our own platform, using a smartphone-enabled app. The aim is to remotely support a patient’s self-management, collect patient reported outcomes (PROMs) and facilitate patient-department communication. We describe the development of the app and early experience of use. Methods We conducted stakeholder meetings with expert patients, clinicians and app developers. In 2015 we launched a pilot app. Following user feedback, a full version of the app was launched in September 2018. In compliance with EU General Data Protection Regulation (GDPR) laws, it currently works as a standalone tool separate to hospital Electronic Health Record (EHR) systems at King's College Hospital. App awareness took place through clinic appointments and a patient educational event. Patients download and register through Android or iOS operated devices. Basic information and explicit consent for data use are gathered. Data are stored on a cloud-based platform accessible to the clinical team and extracts anonymised for analysis. Results 301 patients registered with the app in the first year since launch. Mean age was 44 years (Median 42.5 (IQR 35-53), Range 16-76) slightly younger than that of our local cohort. Clinical enquiries recorded via email have steadily increased since the app’s inception, rising from 2 throughout September 2018 to 209 in September 2019. Almost 25% of patients entered PROMs. These were performed on 115 occasions by 70 different patients (Median 1, Range 1-12). 52 (17.3%) patients used the app to store medication reminders. User feedback has identified positive aspects: links to patient education resources, medication reminders and rapid direct clinical communication. Negative aspects include: no link to the EHR system, inability to change or view appointments, inability to request blood tests. Conclusion We have demonstrated in this project that an app is feasible to use in a rheumatology clinical practice setting, providing a mechanism for collecting patient information and enabling self-management. Use of healthcare apps is clearly not for everyone, with only a minority of our patients using our platform. For apps to be sustainable they need to be of targeted benefit with proportionate investment. A key future strategy is to strengthen our self-management interface and integrate with our EHR systems. Disclosures B.D. Clarke None. L. James None. H. Lapham None. C. Congreve None. S. Steer None. N. Alaghband None. J.B. Galloway Grants/research support; J.G. receives a grant from Pfizer to support the development of this app.

Background The National Health Service caters to a variety of rheumatology patients from increasingly diverse multi-ethnic backgrounds. Despite this, societal, organisational and personal barriers remain across the UK. These are known to directly and indirectly influence access to care although no inference can be generalised at a local level. Our south London trust has one of the highest non-white patient bases in the UK, hence our interest in wanting to explore the cultural differences around delivery of care. We set out to use the national inflammatory arthritis audit (NEIAA) data from our department to ensure equitable service provision and delivery using quality improvement methodology. Methods The NEIAA data for our trust observes performance across the seven NICE quality indicators for rheumatoid arthritis. Of interest was evaluation of standards 1 to 6, as too few data existed for standard 7. Ethnicity was coded according to the NEIAA categories as white or non-white. Differences by disease severity indicators were analysed. A descriptive analysis was performed with an understanding that no assumptions or statistical interpretations could be made to these observed differences. Results A total of 471 patients had data available. Of these, 124 (26%) had a diagnosis of early inflammatory arthritis, of whom 34 (27%) were non-white and 80 (73%) were white. Non-white patients were younger, more were seropositive, had a higher baseline DAS28, worse MSK-HQ scores, worse mental health scores and worse HAQ scores. Non-white patients were less likely to have a patient reported outcome recorded. Attainment of quality standards 1, 2, 3 and 6 had equiproportionate representation of non-white and white patients. Standards 4 (provision of education) and 5 (agreement of treatment target) demonstrated fewer non-white patients meeting the target. Standard 5 demonstrated the most disparity. 83% of white patients had an agreed target compared to 47% of non-white (Odds ratio 5.6 (CI 2.2-14.1)). To describe this, our non-white patients were more than 5 times less likely to have an agreed treatment target. Conclusion Cultural differences exist in health-seeking behaviour, verbal language, written comprehension and in unconscious bias. The NEIAA results within our trust suggest differences exist by ethnic groupings in early arthritis care. Although challenges and taboos remain in discussing these variations, more work needs to be undertaken to explore healthcare disparities and why these occur. Research within this field is limited to date. We plan to adopt a quality improvement approach using stakeholder engagement meetings, process-mapping and driver diagrams to evaluate how best to achieve change. Disclosures L. James None. B.D. Clarke None. R. Salerno None. A. Audu None. S. Steer None. J.B. Galloway None.

Background\ud Previous studies of radiological damage in rheumatoid arthritis (RA) have used candidate-gene approaches, or evaluated single genome-wide association studies (GWAS). We undertook the first meta-analysis of GWAS of RA radiological damage to: (1) identify novel genetic loci for this trait; and (2) test previously validated variants.\ud \ud Methods\ud Seven GWAS (2,775 RA cases, of a range of ancestries) were combined in a meta-analysis. Radiological damage was assessed using modified Larsen scores, Sharp van Der Heijde scores, and erosive status. Single nucleotide polymophsim (SNP) associations with radiological damage were tested at a single time-point using regression models. Primary analyses included age and disease duration as covariates. Secondary analyses also included rheumatoid factor (RF). Meta-analyses were undertaken in trans-ethnic and European-only cases.\ud \ud Results\ud In the trans-ethnic primary meta-analysis, one SNP (rs112112734) in close proximity to HLA-DRB1, and strong linkage disequilibrium with the shared-epitope, attained genome-wide significance (P = 4.2x10-8). In the secondary analysis (adjusting for RF) the association was less significant (P = 1.7x10-6). In both trans-ethnic primary and secondary meta-analyses 14 regions contained SNPs with associations reaching P

Rheumatoid Arthritis (RA) pharmacotherapy may impact mental health (MH) outcomes by improving pain and stiffness; and potentially via targeting inflammatory processes common to RA and depression. The objectives of this review were to i) ascertain the frequency of MH assessment in RA pharmacotherapy trials; ii) quantify the efficacy of RA pharmacotherapy efficacy on MH outcomes; iii) explore the clinical and demographic factors related to MH outcomes.\ud \ud CENTRAL, PsychINFO, Web of Science, Medline, Embase and CINAHL were systematically searched from inception to March 2017 for randomised trials of disease‐modifying anti‐rheumatic drugs (DMARDs) in adult RA patients. The primary outcome was MH; self‐reported physical health was extracted as a secondary outcome. Pairwise meta‐analysis (PMA) created pooled effect sizes and 95%CIs for comparisons of all treatments versus comparators (active or placebo). Network meta‐analysis (NMA) provided effect size estimates of targeted biologic DMARDs (bDMARDs) versus conventional synthetic DMARDs (csDMARDs) using indirect comparisons of different treatment modalities.\ud \ud 71 eligible studies were identified. 57 studies were included in the PMA, representing 23,535 patients. bDMARDs showed small effects on MH (standardised mean difference (SMD) versus csDMARDs = 0.19 to 0.30), and moderate effects on self‐reported physical health (SMD versus csDMARDs = 0.46 to 0.50), with NMA determining no significant differences in effectiveness between bDMARD mode of action on either outcome.\ud \ud Effective pharmacotherapy alone is unlikely to substantially improve MH outcomes for most RA patients. Integrated MH care provided within routine clinical practice is essential to optimise mental and physical health outcomes.

Background Adolescents and young adults (AYA) form one sixth of the world’s population and account for 6% of the world’s global burden of disease. Those with chronic illness are particularly vulnerable. Globally, significant improvements in healthcare related morbidity and mortality have been seen, but not within the 10–24 year old group. Adolescence is a rapidly changing, formative phase of human development; opportunities exist to impact this through restructing care pathways and patient empowerment. Objectives Establish awareness of current national guidance and identify unmet needs in existing rheumatology AYA systems. Methods Interested parties from South East England (South London, Kent, Surrey and Sussex) formed a multi-disciplinary, patient based, co-design initiative (RAYA collaborative) which included representatives from primary/secondary/tertiary care, allied health professionals and a youth worker/patient from the charity sector. Our discussions and an anonymous survey to hospitals in the region, formed the basis of a qualitative and quantitative analysis, which helped gain a holistic insight into the challenges and opportunities in delivering AYA care in our region. Results 15/20 centres, covering an 8 million population, responded; 4 tertiary care hospitals, 11 district general hospitals with 32 responses (19 consultants, 13 senior registrars). 31 (97%) of responders felt that AYA cohort (16–25 years old) required an approach different to that of older adults. 25 (78%) felt there was a need for dedicated AYA services. 23 (72%) and 17 (53%) were aware of UK national guidelinesCQC 2014/NICE NG43 2016 respectively) for transitional/integrated and coordinated care. Barriers to developing dedicated AYA services (% of responders): Not a priority for NHS managers,31 other clinical priorities,31 insufficient patient numbers,22 not cost effective,19 unlikely to be commissioned,19 more research required,13 cohort by diagnosis,13 other ways to deliver care,13 only focus on transitioning patients from paediatrics13 Responders would like assistance in future care delivery through: Clinical toolkit: 63% n=20, Service commissioning toolkit: 43% n=14, Training: 43% n=14, Workshops: 47% n=15. Potential low cost/cost neutral approaches to systems change, cultural change, education and sharing of resource were discussed (see image). Conclusions Improving outcomes for AYA patients through delivering age appropriate care and self advocacy has driven global strategy and guidelines. Our survey identifies that the majority of rheumatologists agree with this, however there is room for improvement regarding awareness and implementation of current guidance. Financial constraints and whole population healthcare delivery has limited change. A systematic, unified approach within regions may help to effect change. There is a demand for the development of clinical and commissioning toolkits and training/workshops to help facilitate this. Reference [1] Global Accelerated Act on for the Health of Adolescents WHO2017. Disclosure of Interest None declared

Objective. The aim of this analysis is to examine the longitudinal impact of symptoms of depression/anxiety on treatment response, long-term disease activity and physical disability in RA.Methods. Secondary analysis of clinical trial data was performed. Data were collected at baseline and at 6-monthly intervals for 2 years. The EuroQoL (EQ-5DTM) indicated depression/anxiety symptom severity. Our primary outcomes of interest were (i) DAS-28 and (ii) physical disability measured via the HAQ. Secondary outcomes were: tender and swollen joint counts, patient global assessment, ESR and odds of reaching clinical remission. Multilevel models were used to assess the impact of baseline and persistent depression/anxiety on outcomes over 2 years.Results. Data from 379 patients were included. After adjusting for covariates, baseline depression/anxiety symptoms were associated with increased DAS-28 outcomes and increased tender joint counts. Persistent depression/anxiety symptoms were associated with increased DAS-28 scores, HAQ scores, tender joint counts and patient global assessment of disease activity, and reduced odds of reaching clinical remission. Patients with symptoms of depression/anxiety at baseline also showed a 50% reduction in prednisolone treatment effect, in comparison with patients with no symptoms of depression/anxiety at baseline.Conclusion. Baseline and persistent symptoms of depression/anxiety are associated with poorer health outcomes over time, as well as reduced treatment response. Mental health should be routinely measured both in clinical practice and in research, and managed alongside rheumatological disease to optimize health outcomes. Further research is required to examine whether treatment of mental disorders can improve rheumatological outcomes.

ObjectiveThe assessment of health-related quality-of-life (HRQoL) in rheumatoid arthritis (RA) is becoming increasingly common in both research and clinical practice. One of the most widely used tools for measuring HRQoL is the Medical Outcomes Study 36-item Short-Form Health Survey (SF-36). We conducted a systematic review examining the impact of RA on HRQoL, measured through the SF-36.MethodsMEDLINE and Embase were searched for observational studies reporting mean and standard deviation scores for each domain of the SF-36 in adult RA patients. Studies were reviewed in accordance with PRISMA guidelines, and a random-effects meta-analysis was performed.ResultsIn total, 31 studies were eligible for inclusion in the meta-analysis, including 22,335 patients. Meta-analyses found that pooled mean HRQoL score for the SF-36 physical component summary was 34.1 (95% CI: 22.0–46.1) and mental component summary was 45.6 (95% CI: 30.3–60.8). Increased age was associated with reduced physical function and physical component summary (PCS) scores but improved mental health and mental component summary (MCS) scores. Female gender was associated with improved scores on role physical, bodily pain and PCS but reduced mental health and MCS scores. Longer disease duration was associated with improved MCS. Patients with RA have a substantially reduced HRQoL in comparison to both other physical illnesses and in comparison to normative datasets from UK and USA populations.ConclusionsRA has a substantial impact on HRQoL. This supports recent NICE guidelines stipulating that RA patients should be regularly assessed for the impact their disease has on HRQoL and appropriate management provided.

Objective: To assess the feasibility and acceptability of routine web-based screening in general hospital settings, and describe the level of common mental disorder. Method: A service development platform to integrate mental and physical healthcare was implemented in six specialties (rheumatology, limb reconstruction, hepatitis C, psoriasis, adult congenital heart disease (ACHD), chronic pain) across three general hospitals in London, UK. Under service conditions, patients completed a web-based questionnaire comprising mental and physical patient-reported outcome measures, whilst waiting for their appointment. Feasibility was quantified as the proportion of patients who completed the questionnaire. Acceptability was quantified as the proportion of patients declining screening, and the proportion requiring assistance completing the questionnaire. The prevalence of probable depression and anxiety was expressed as the percentage of cases determined by the Patient Health Questionnaire-9 and Generalised Anxiety Disorder Questionnaire-7. Results: The proportion of patients screened varied widely across specialties (40.1-98.2%). The decline rate was low (0.6-9.7%) and the minority required assistance (11.7-40.4%). The prevalence of probable depression ranged from 60.9% in chronic pain to 6.6% in ACHD. The prevalence of probable anxiety ranged from 25.1% in rheumatology to 11.4% in ACHD. Conclusion: Web-based screening is acceptable to patients and can be effectively embedded in routine practice. General hospital patients are at increased risk of common mental disorder, and routine screening may help identify need, inform care and monitor outcomes.

Objective. There is substantial uncertainty regarding the prevalence of depression in RA. We conducted a systematic review aiming to describe the prevalence of depression in RA.Methods. Web of Science, PsycINFO, CINAHL, Embase, Medline and PubMed were searched for cross-sectional studies reporting a prevalence estimate for depression in adult RA patients. Studies were reviewed in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines and a meta-analysis was performed.Results. A total of 72 studies, including 13 189 patients, were eligible for inclusion in the review. Forty-three methods of defining depression were reported. Meta-analyses revealed the prevalence of major depressive disorder to be 16.8% (95% CI 10%, 24%). According to the PHQ-9, the prevalence of depression was 38.8% (95% CI 34%, 43%), and prevalence levels according to the HADS with thresholds of 8 and 11 were 34.2% (95% CI 25%, 44%) and 14.8% (95% CI 12%, 18%), respectively. The main influence on depression prevalence was the mean age of the sample.Conclusion. Depression is highly prevalent in RA and associated with poorer RA outcomes. This suggests that optimal care of RA patients may include the detection and management of depression.

Rheumatoid arthritis (RA) is a heterogeneous disease that varies markedly in its severity. There is, therefore, a key research need to develop methods that can predict an individual’s likely RA severity at disease onset, which would enable treatment to be tailored accordingly. A number of different prognostic factors for RA severity have been identified. These include environmental (such as smoking and alcohol consumption), genetic (such as the HLA-DRB1 alleles and polymorphisms in the IL1 locus), serological (rheumatoid factor and antibodies to citrullinated protein antigens) and biochemical (such as matrix metalloproteinases) factors. In this review, the authors discuss these prognostic factors in detail, outlining the evidence supporting them and focusing on how they have been combined in prognostic modeling to predict the likely severity of an individual’s RA phenotype.

Introduction: The K-BILD is a validated HRQOL questionnaire. We previously reported the MID is 8 units. Item responses are now transformed to logits rather than using raw responses, as this is potentially a more linear scale (Patel A, JCE 2015;68;1019). The aim of this study was to re-evaluate the K-BILD MID using the logit scale. Methods: 57 patients with ILD (17-IPF) completed the K-BILD on 2 occasions. At the second visit patients also completed a Global rating of change of health status questionnaire (GRCQ). The MID was calculated as the mean of 4 different methods (anchors): GRCQ, 7-12% change in FVC, 1 SEM and effect size (ES) of 0.3. Results: The mean(SD) K-BILD Total score for all patients was 55.3(15.6). 36 patients reported a change in their condition on the GRCQ. There was a significant change in K-BILD score in patients reporting a change in GRCQ; mean(SD) 57.0(13.6) vs. 50.0(9.7); mean diff 7.0; 95% CI 3.0 to 11.0; p

Background Polymorphisms of the peptidylarginine deiminase type 4 ( PADI4 ) gene confer susceptibility to rheumatoid arthritis (RA) in East Asian people. However, studies in European populations have produced conflicting results. This study explored the association of the PADI4 genotype with RA in a large UK Caucasian population. Methods The PADI4_94 (rs2240340) single nucleotide polymorphism (SNP) was directly genotyped in a cohort of unrelated UK Caucasian patients with RA (n=3732) and population controls (n=3039). Imputed data from the Wellcome Trust Case Control Consortium (WTCCC) was used to investigate the association of PADI4_94 with RA in an independent group of RA cases (n=1859) and controls (n=10 599). A further 56 SNPs spanning the PADI4 gene were investigated for association with RA using data from the WTCCC study. Results The PADI4_94 genotype was not associated with RA in either the present cohort or the WTCCC cohort. Combined analysis of all the cases of RA (n=5591) and controls (n=13 638) gave an overall OR of 1.01 (95% CI 0.96 to 1.05, p=0.72). No association with anti-CCP antibodies and no interaction with either shared epitope or PTPN22 was detected. No evidence for association with RA was identified for any of the PADI4 SNPs investigated. Meta-analysis of previously published studies and our data confirmed no significant association between the PADI4_94 genotype and RA in people of European descent (OR 1.06, 95% CI 0.99 to 1.13, p=0.12). Conclusion In the largest study performed to date, the PADI4 genotype was not a significant risk factor for RA in people of European ancestry, in contrast to Asian populations.

Background This study aimed to assess the accuracy of the Short-Form Health Survey (SF-36) mental health subscale (MH) and mental component summary (MCS) scores in identifying the presence of probable major depressive or anxiety disorder in patients with rheumatoid arthritis. Methods SF-36 data were collected in 100 hospital outpatients with rheumatoid arthritis. MH and MCS scores were compared against depression and anxiety data collected using validated measures as part of routine clinical practice. Sensitivity and specificity of the SF-36 were established using receiver operating characteristic (ROC) curve analysis, and area under the curve (AUC) compared the performance of the SF-36 components with the 9-item Patient Health Questionnaire (PHQ9) for depression and the 7-item Generalised Anxiety Disorder (GAD7) questionnaire for anxiety. Results The MH with a threshold of ≤52 had sensitivity and specificity of 81.0 and 71.4 % respectively to detect anxiety, correctly classifying 73.5 % of patients with probable anxiety disorder. A threshold of ≤56 had sensitivity and specificity of 92.6 and 73.2 % respectively to detect depression, correctly classifying 78.6 % of patients, and the same threshold could also be used to detect either depression or anxiety with a sensitivity of 87.9 %, specificity of 76.9 % and accuracy of 80.6 %. The MCS with a threshold of ≤35 had sensitivity and specificity of 85.7 and 81.9 % respectively to detect anxiety, correctly classifying 82.8 % of patients with probable anxiety disorder. A threshold of ≤40 had sensitivity and specificity of 92.3 and 70.2 % respectively to detect depression, correctly classifying 76.3 % of patients. A threshold of ≤38 could be used to detect either depression or anxiety with a sensitivity of 87.5 %, specificity of 80.3 % and accuracy of 82.8 %. Conclusion This analysis may increase the utility of a widely-used questionnaire. Overall, optimal use of the SF-36 for screening for mental disorder may be through using the MCS with a threshold of ≤38 to identify the presence of either depression or anxiety. Electronic supplementary material The online version of this article (doi:10.1186/s12891-016-1083-y) contains supplementary material, which is available to authorized users.

Connective tissue disease (CTD) and sickle cell disease (SCD) are diverse group of disorders; however, both of these diseases are characterized by underlying chronic inflammation. CTD is perceived to have a higher incidence and to affect the disease severity in SCD. Objectives: We seek to describe prevalence of autoimmunity and CTD and itsimpact on SCD disease severity as this is not well described in the literature. Methods: We retrospectively reviewed the medical records of 722 patients with SCD, seen over an 11 year period followed at a tertiary care hospital in London, UK. During the last 2 years of the study, number of hospitalizations and length of hospital stay were compared in patients with SCD with and without CTD. Results: In the study cohort, hemoglobin SS was the most common genotype (n = 451; 62%) and 411 (57%) were female. Twenty-three patients (3.1% had documented evidence of CTD, with rheumatoid arthritis (n = 14; 2%) and systemic lupus erythematosus (n = 2; 0.3%) being the most common. Antinuclear antibody was present in 108 (15%) of the patients and anti-smooth muscle antibody was present in 60 (8%). The mean number of hospitalizations (1.9 ± 2.7 vs. 1.5 ± 2.7) and mean length of hospital stay (6 days ± 4.1 vs. 7 days ± 11.4) were not different between those with or without autoimmunity and/or CTD. Avascular necrosis was the most common non-CTD musculoskeletal complication, affecting 72 (10%) patients. Conclusion: Our study suggests that positive autoimmune serology and CTD were more common in SCD compared to non-SCD population of similar ethnic background; however, presence of CTD does not appear to affect the SCD severity. The high frequency of CTD and overlapping of clinical symptoms suggest a need for diagnostic vigilance in diagnosing CTD in patients with SCD.

BACKGROUND: Rheumatoid arthritis (RA) treatment paradigms have shifted over the last two decades. There has been increasing emphasis on combination disease modifying anti-rheumatic drug (DMARD) therapy, newer biologic therapies have become available and there is a greater focus on achieving remission. We have evaluated the impact of treatment changes on disease activity scores for 28 joints (DAS28) and disability measured by the health assessment questionnaire scores (HAQ).METHODS: Four cross-sectional surveys between 1996 and 2014 in two adjacent secondary care rheumatology departments in London evaluated changes in drug therapy, DAS28 and its component parts and HAQ scores (in three surveys). Descriptive statistics used means and standard deviations (SD) or medians and interquartile ranges (IQR) to summarise changes. Spearman's correlations assessed relationships between assessments.RESULTS: 1324 patients were studied. Gender ratios, age and mean disease duration were similar across all cohorts. There were temporal increases in the use of any DMARDs (rising from 61% to 87% of patients from 1996-2014), combination DMARDs (1% to 41%) and biologic (0 to 32%). Mean DAS28 fell (5.2 to 3.7), active disease (DAS28 > 5.1) declined (50% to 18%) and DAS28 remission (DAS28 CONCLUSIONS: Treatment intensity has increased over time, disease activity has fallen and there are more remissions. However, these improvements in controlling synovitis have not resulted in comparable reductions in disability measured by HAQ. As a consequence the relationship between DAS28 and HAQ has become weaker over time. Although the reasons for this divergence between disease activity and disability are uncertain, focussing treatment entirely in suppressing synovitis may be insufficient.

Rheumatoid arthritis (RA) varies over time in individual patients and there are marked differences between patients in its impact and progression. The course of RA is therefore unique to each individual patient and is affected by the overall pattern of disease; many patients have classical polyarticular disease but there is also a range of subtypes, such as fibromyalgic and polymyalgic disease. Some patients with RA enter a period of sustained remission; this varies between 10% and 36% of cases; its frequency is mainly influenced by the different approaches to studying RA patients over time, and does not represent a true difference in disease outcome. Most patients have persisting synovial inflammation and disease activity scores average between 3 and 4; there is some evidence that inflammation is less marked in late RA. Persisting synovitis results in increasing disability - this worsens by an average of 0.6% each year - and in joint damage, which increases by an average of 2% each year. Comorbidities and extra-articular features are commonplace: about one-third of patients, respectively, have associated cardiovascular disease, lung disease or extra-articular features, although severe extra-articular problems like vasculitis affect only about 10% of patients. Some aspects of the course of RA are influenced by genetic risks; currently these are only weak predictors but it is anticipated their value will increase with time.

Rheumatoid arthritis (RA) is associated with reduced lifespan and shortened telomere length in lymphocytes, but the mechanism underlying this is unclear. Telomere loss in white blood cells (WBC) is accelerated by oxidative stress and inflammation in vitro. It was postulated that the accelerated WBC telomere shortening in RA occurs as a result of exposure to chronic inflammation.To measure telomere terminal restriction fragment (TRF) length in a large cohort of RA cases and healthy controls, to explore associations of TRF length with features of disease and with RA-associated HLA-DRB1 alleles.WBC and TRF length were measured by Southern blot in DNA from 176 hospital-based RA cases satisfying the 1987 American College of Rheumatology criteria and from 1151 controls. TRF length was compared between cases and controls, and the effects of disease duration, severity and HLA-DRB1 alleles encoding the shared epitope (SE) were assessed.Age- and sex-adjusted TRF length was significantly shorter in RA cases compared with controls (p0.001). There was no association between age- and sex-adjusted TRF length and disease duration, C reactive protein or Larsen score. The presence of one or more SE-encoding alleles was associated with reduced adjusted TRF length in RA cases (SE positive vs SE negative cases, p=0.038), but not in controls.The reduced TRF length in a large group of patients with RA compared with controls has been shown. The reduction is apparently independent of disease duration and markers of disease severity, but is influenced by HLA-DRB1 genotype.

Our aim was to establish whether alcohol protects against RA development and to determine whether this effect is influenced by alcohol dose, duration and serological status through systematically reviewing the literature and undertaking a meta-analysis.We searched Medline/EMBASE (1946 to July 2012) using the terms rheumatoid arthritis.mp or arthritis, rheumatoid/ and alcohol.mp or ethanol/. Manuscript bibliographies were reviewed. Observational studies were included that were case-control/cohort, examined the relationship between alcohol and RA risk and reported or allowed the calculation of effect size data [odds ratios (ORs)/relative risks (RRs) with 95% CIs] in drinkers vs non-drinkers. A random-effects model was used to estimate pooled ORs/RRs. Dose-risk relationships were evaluated by trend tests. RESULTS. Nine studies (from 893 articles) met our inclusion criteria, comprising six case-control (3564 cases; 8477 controls) and three cohort studies (444 RA cases; 84 421 individuals). A significant protective effect of alcohol on RA risk was observed-summary OR for RA in drinkers vs non-drinkers 0.78 (95% CI 0.63, 0.96). This effect was confined to ACPA-positive RA-summary OR 0.52 (95% CI 0.36, 0.76), with no significant risk reduction seen for ACPA-negative RA-summary OR 0.74 (95% CI 0.53, 1.05). Subgroup analysis by study design identified a significant relationship in case-control but not cohort studies.Alcohol intake is inversely associated with ACPA-positive RA, suggesting a protective effect. As this finding is confined to case-control studies further research is required with prospective cohort studies incorporating ACPA status to confirm this relationship.

Rationale Health status is impaired in patients with interstitial lung disease (ILD). There is a paucity of tools that assess health status in ILD. The objective of this study was to develop and validate the King9s Brief Interstitial Lung Disease questionnaire (K-BILD), a new health status measure for patients with ILD. Methods Patients with ILD were recruited from outpatient clinics. The development of the questionnaire consisted of three phases: item generation; item reduction, allocation to domains by factor analysis, Rasch analysis to create unidimensional scales and validation; and repeatability testing. Results 173 patients with ILD (49 with idiopathic pulmonary fibrosis) completed a preliminary 71-item questionnaire. 56 items were removed due to redundancy, low factor loadings or poor fit to the Rasch model. The final version of the K-BILD questionnaire consisted of 15 items and three domains (breathlessness and activities, chest symptoms and psychological). Internal consistency assessed with Cronbach9s α coefficient was 0.94 for the K-BILD total score. Concurrent validity of the K-BILD questionnaire was high compared with St George9s Respiratory Questionnaire (r=0.90) and moderate with lung function (vital capacity, r=0.50). The K-BILD questionnaire was repeatable over 2 weeks (n=44), with intraclass correlation coefficients for domains and total score 0.86–0.94. The K-BILD construct validity for patients with idiopathic pulmonary fibrosis was similar to that of other ILDs. Conclusion The K-BILD questionnaire is a brief, valid, self-completed health status measure for ILD. It could be used in the clinic to assess ILD from the patients9 perspective.

Contains fulltext : 98409.pdf (Publisher’s version ) (Closed access) OBJECTIVE: Recently, a functional PTPN22 variant (R263Q; rs33996649) was found to be associated with systemic lupus erythematosus (SLE). This study was undertaken to analyze the influence of this polymorphism on the risk of rheumatoid arthritis (RA). METHODS: RA patients (n = 5,579) were recruited from outpatient clinics from 6 different countries (Spain, New Zealand, the UK, Norway, The Netherlands, and Germany). Healthy controls (n = 5,392) were recruited from the same areas. There was 100% power to detect an effect equivalent to that observed in SLE. Samples were genotyped for the PTPN22 R263Q (rs33996649) and PTPN22 R620W (rs2476601) polymorphisms using a TaqMan 5'-allele discrimination assay. The effect of the R263Q variant was analyzed in isolation and in combination with the effect of R620W, using Unphased and Stata 10 software. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were determined. RESULTS: The minor allele A of PTPN22 R263Q was significantly associated with a lower risk of RA in the pooled analysis of the 6 populations (P = 0.016, Mantel-Haenszel pooled OR 0.80 [95% CI 0.67-0.96]), independent of the effect of the R620W polymorphism. Both polymorphisms had an additive effect. The more RA risk alleles carried (R263Q G allele, R620W T allele), the higher the RA risk (for 2 versus 1 risk allele P = 0.014, OR 1.28 [95% CI 1.05-1.55], for 3 versus 1 risk allele P = 6.67 x 10(-11) , OR 2.01 [1.63-2.48], and for 4 versus 1 risk allele P = 6.50 x 10(-11) , OR 3.55 [2.42-5.20]). CONCLUSION: Our findings indicate that the minor allele of the PTPN22 R263Q polymorphism is associated with a lower risk of RA. This association is independent of the well-established association between PTPN22 R620W and RA. Both polymorphisms have an additive effect on the risk of RA.

Background: The acute-phase increase in serum C-reactive protein (CRP) is used to diagnose and monitor infectious and inflammatory diseases. Little is known about the influence of genetics on acute-phase CRP, particularly in patients with chronic inflammation. Methods and Findings: We studied two independent sets of patients with chronic inflammation due to rheumatoid arthritis (total 695 patients). A tagSNP approach captured common variation at the CRP locus and the relationship between genotype and serum CRP was explored by linear modelling. Erythrocyte sedimentation rate (ESR) was incorporated as an independent marker of inflammation to adjust for the varying levels of inflammatory disease activity between patients. Common genetic variants at the CRP locus were associated with acute-phase serum CRP (for the most associated haplotype: p=0.002, p,0.0005, p,0.0005 in patient sets 1, 2, and the combined sets, respectively), translating into an approximately 3.5-fold change in expected serum CRP concentrations between carriers of two common CRP haplotypes. For example, when ESR=50 mm/h the expected geometric mean CRP (95% confidence interval) concentration was 43.1 mg/l (32.1–50.0) for haplotype 1 and 14.2 mg/l (9.5–23.2) for haplotype 4. Conclusions: Our findings raise questions about the interpretation of acute-phase serum CRP. In particular, failure to take into account the potential for genetic effects may result in the inappropriate reassurance or suboptimal treatment of patients simply because they carry low-CRP–associated genetic variants. CRP is increasingly being incorporated into clinical algorithms to compare disease activity between patients and to predict future clinical events: our findings impact on the use of these algorithms. For example, where access to effective, but expensive, biological therapies in rheumatoid arthritis is rationed on the basis of a DAS28-CRP clinical activity score, then two patients with identical underlying disease severity could be given, or denied, treatment on the basis of CRP genotype alone. The accuracy and utility of these algorithms might be improved by using a genetically adjusted CRP measurement. Please see later in the article for the Editors’ Summary.

Objective A recent meta-analysis of published genome-wide association studies (GWAS) in populations of European descent reported novel associations of markers mapping to the CD40, CCL21 and CDK6 genes with rheumatoid arthritis (RA) susceptibility while a large-scale, case-control association study in a Japanese population identified association with multiple single nucleotide polymorphisms (SNPs) in the CD244 gene. The aim of the current study was to validate these potential RA susceptibility markers in a UK population. Methods A total of 4 SNPs (rs4810485 in CD40, rs2812378 in CCL21, rs42041 in CDK6 and rs6682654 in CD244) were genotyped in a UK cohort comprising 3962 UK patients with RA and 3531 healthy controls using the Sequenom iPlex platform. Genotype counts in patients and controls were analysed with the chi(2) test using Stata. Results Association to the CD40 gene was robustly replicated (p=2 x 10(-4), OR 0.86, 95% CI 0.79 to 0.93) and modest evidence was found for association with the CCL21 locus (p=0.04, OR 1.08, 95% CI 1.01 to 1.16). However, there was no evidence for association of rs42041 (CDK6) and rs6682654 (CD244) with RA susceptibility in this UK population. Following a meta-analysis including the original data, association to CD40 was confirmed (p=7.8 x 10(-8), OR 0.87 (95% CI 0.83 to 0.92). Conclusion In this large UK cohort, strong association of the CD40 gene with susceptibility to RA was found, and weaker evidence for association with RA in the CCL21 locus.

INTRODUCTION: Genome wide association studies, replicated by numerous well powered validation studies, have revealed a large number of loci likely to play a role in susceptibility to many multifactorial diseases. It is now well established that some of these loci are shared between diseases with similar aetiology. For example, a number of autoimmune diseases have been associated with variants in the PTPN22, TNFAIP3 and CTLA4 genes. Here we have attempted to define overlapping genetic variants between rheumatoid arthritis (RA), type 1 diabetes (T1D) and coeliac disease (CeD). METHODS: We selected eight SNPs previously identified as being associated with CeD and six T1D-associated SNPs for validation in a sample of 3,962 RA patients and 3,531 controls. Genotyping was performed using the Sequenom MassArray platform and comparison of genotype and allele frequencies between cases and controls was undertaken. A trend test P-value < 0.004 was regarded as significant. RESULTS: We found statistically significant evidence for association of the TAGAP locus with RA (P = 5.0 × 10-4). A marker at one other locus, C1QTNF6, previously associated with T1D, showed nominal association with RA in the current study but did not remain statistically significant at the corrected threshold. CONCLUSIONS: In exploring the overlap between T1D, CeD and RA, there is strong evidence that variation within the TAGAP gene is associated with all three autoimmune diseases. Interestingly a number of loci appear to be specific to one of the three diseases currently studied suggesting that they may play a role in determining the particular autoimmune phenotype at presentation.

Updated guidance from the UK National Institute for Health and Clinical Excellence on the use of tumor necrosis factor (TNF) antagonists for rheumatoid arthritis recommends that patients who do not respond to initial anti-TNF therapy should not switch to another TNF inhibitor. In this Viewpoint, the authors discuss the rationale and controversies surrounding this recommendation.

Method: A systematic literature review (using PRISMA guidelines) identified factors associated with the development and severity of AWS used to develop a 10-item scale to predict alcohol dependent patients at risk for developing complicated AWS (i.e., seizures and DT). We prospectively recruited all consecutively hospitalized subjects to the general medicine units over a 3-mo period to test PAWSS' validity and reliability. Subjects were independently and blindly assessed daily with PAWSS, CIWA-Ar, and clinical monitoring throughout their admission to determine the presence and severity of AWS. Results: 409 patients were tested and grouped by PAWSS score: Group A included those with a PAWSS b 4 and were considered to be at low risk for AWS; while subjects in Group B obtained a PAWSS N 4 andwereconsideredat highriskforcomplicatedAWS.Twopatientsin Group A experienced elevated CIWA scores or were treated for AWS. As predicted, all but two subjects in Group B required pharmacological treatment for AWS. The results of this study suggest that, using a PAWSS cut-off of 4, the tool's sensitivity is 93.5%, specificity is 99.5%, positive predictive value is 93.5%, and negative predictive value is 99.5%. Conclusion: PAWSS appears to have excellent psychometric characteristics and predictive value among medically-ill inpatients, helping clinicians identify those at risk for complicated AWS and allowing for timely prophylactic treatment. The use of PAWSS will minimize the excessive use of medications in those at low risk for complicated AWS, thus minimizing undesirable side effects.

Genetic factors are increasingly recognized to have an important contribution to the occurrence of both inflammatory and noninflammatory rheumatic disease. Although identifying the specific genetic mechanisms involved in the rheumatic diseases continues to present considerable challenges, the prospect of identifying individual gene action has been brought closer by a number of recent developments. These include newer approaches to phenotype definition, refinements in statistical tools for analysis, and the advent of newer technologies, including the use of microarrays. In this article, we review some of these developments together with the recent literature on the contribution of both broad and specific genetic factors to the spectrum of rheumatic disease. We also consider contemporary opinions on the potential impact of genetic discoveries to human health.

Background Depression is highly prevalent in RA and is associated with increased mortality, disability and healthcare costs [1, 2]. There is limited evidence assessing the longitudinal impact of depression on RA outcomes, particularly objectively-reported clinical outcomes. Objectives To assess the impact of persistent depression on physical health outcomes over a 2-year follow-up period. Methods A secondary data analysis of a clinical trial (CARDERA) was performed [3]. Depression and physical health outcomes were measured at baseline and 6-montly intervals for 2-years. Depression was measured using the EQ-5D, and patients were categorised into 4 groups: 1) never depressed; 2) depressed at 50% of time-points; and 4) depressed at every time-point. Physical health outcomes were: Larsen score; tender joint count (TJC); swollen joint count (SJC); ESR; assessor and patient global assessments (AGA/PGA); HAQ; pain; and DAS-28. Results Data was available for 379 patients. Patients9 mean age was 54.1 (12.3), and 68.3% of the sample were female. In total, 25.9% were never depressed, 36.9% were depressed 50% of the time, and 15.8% were depressed at every time-point. Conclusions Increasing persistence of depression over time tends to be associated with poor physical health outcomes, with discordance between subjectively and objectively measured outcomes. These findings have significant implications: mental health should be measured and monitored throughout the course of treatment [4]; DAS-28 scores may be inflated in depressed patients, which needs to be considered when making treatment decisions. References Matcham F et al. The prevalence of depression in Rheumatoid Arthritis: A systematic review and meta-analysis. Rheumatology 2013; 52: 2136-48. Bruce T. Comorbid depression in rheumatoid arthritis: Pathophysiology and clinical implications. Current Psychiatry Reports 2008; 10: 258-64. Choy EHS et al. Factorial randomised controlled trial of glucocorticoids and combination disease modifying drugs in early rheumatoid arthritis. Ann Rheum Dis 2008; 67: 656-63. Rayner L et al. Embedding integrated mental health assessment and management in general hospital settings: feasibility, acceptability and the prevalence of common mental disorder. Gen Hosp Psychiatr (in press), doi: 10.1016/j.genhosppsych.2013.12.004. Disclosure of Interest : None declared DOI 10.1136/annrheumdis-2014-eular.2878

Background Several studies have tested the hypothesis that RA susceptibility variants associate with radiological progression. Their findings are often not replicated; additionally they have examined only a proportion of risk loci and evaluated each locus separately, despite limited power. Two recent meta-analyses of genome-wide association studies have expanded the number of genetic loci and HLA amino acid polymorphisms associated with RA susceptibility [1, 2]. Our aim was to establish if these variants correlated with radiological progression in early active RA patients enrolled to a clinical trial. We evaluated their association both individually and cumulatively, using a weighted genetic risk score (wGRS) combining risk loci. Objectives To establish if genetic predictors of RA susceptibility also associate with radiological progression in early active RA. Methods We evaluated 421 RA patients previously enrolled to the Combination Anti-Rheumatic Drugs in Early RA (CARDERA) trial. Hand/feet radiographs were read for modified Larsen scores every 6 months for 2 years. We evaluated the association of validated genetic risk variants (69 SNPs, 17 four-digit HLA-DRB1 alleles and polymorphisms in 6 HLA amino acid positions) with log-transformed Larsen scores over time using a linear mixed-effects model. Log e (Larsen score + 1) was the response variable. Time, treatment, age, disease duration, ACPA status, genotype and a genotype*time interaction, were the fixed-effects predictor variables. Genotype was coded additively. All β-estimates were back-transformed to the original Larsen scale. The genotype*time β provided information on the annual increase in Larsen score per risk allele copy relative to the reference genotype; P -values for this term provided information on the variant9s role in radiological progression. We assessed the association between a wGRS incorporating susceptibility SNPs and radiological progression by replacing the linear model9s genotype term with a wGRS. Ethical approval was obtained; all patients provided consent. Results Two SNPs, one HLA-DRB1 allele and two HLA-DRβ1 protein amino acid polymorphisms had P -values P =0.0680). Conclusions RA susceptibility loci did not have a clinically relevant association with radiological progression in European ancestry, early, active RA patients recruited to this trial. This suggests the genetic architectures of RA susceptibility and severity differ. References Okada Y et al. Genetics of rheumatoid arthritis contributes to biology and drug discovery. Nature 2013; [Epub ahead of print]. Raychaudhuri S et al. Five amino acids in three HLA proteins explain most of the association between MHC and seropositive rheumatoid arthritis. Nat Genet 2012;44:291-6. Acknowledgements Arthritis Research UK (Grant Reference Number 19739 to ICS); National Institute for Health Research (NIHR) Biomedical Research Centre at Guy9s and St Thomas9 NHS Foundation Trust in partnership with King9s College London. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.5018

Background Prescribing patterns in Rheumatoid Arthritis have evolved over recent decades. There is now clear evidence that combination DMARDs and biologics can acheive better disease control. This is guided by the treat to target initiative aiming for remission in all patients. Objectives We have used observational data to determine changes in prescribing patterns since 1996. We set out to describe the % of patients with RA being treated with individual DMARDs, combination therapy, systemic steroids and biologics. Methods Our study included 1492 RA patients attending two rheumatology centres. They comprised four groups of clinic attenders attending between 1996 and 2013. We collected data on the use of DMARDs, systemic steroids and biologics. Data were also collected on the proportion of patients not receiving any immunosuppressive therapy. Results More patients received immunosuppressive treatment with 14% of all RA patients and 16% of intermediate disease activity group not on any treatment in 2012-13 compared with 32% and 23% in the 1996-97 cohort. Methotrexate remains the most frequently prescribed DMARD across all cohorts, however the more contemporaneous cohorts have higher exposure to hydroxychloroquine, sulfasalazine and leflunomide. Conversely, few patients ( The % of patients treated with combination therapy has increased, however almost half of patients remain on a single DMARD (46%). The proportion of patients treated with biologics has steadily increased from 0 to 1996-97, 4% in 2001-03 to 17% and 21% in the two later cohorts. Systemic steroid use has fluctuated over time, prescribed in 14% in 2012-13. Conclusions Increasing numbers of patients are being treated with immunosuppression. The choice of DMARD has changed from fewer patients being prescribed gold, penicillamine and azathioprine, to more patients being treated with methotrexate, hydroxychloroquine, sulfasalazine and leflunomide. Whilst the uptake of combination DMARD therapy and biologics has increased, approximately half of patients remain on a single DMARD only. This may be due to a number of reasons including physician choice, patient choice and drug intolerance. Further research is needed to explore this issue. There are still patients not on immunosuppression, suggesting that we are not treating to target, and not achieving tighter targeted control in all patients. Further research into why patients who have not achieved remission are not being treated with combination therapy is needed. The role of biologics in moderate disease activity patients to further try and achieve remission needs to be explored. Disclosure of Interest : None declared DOI 10.1136/annrheumdis-2014-eular.5399

Ian C. Scott, Jemma Walker, Jelmar Quist, Sarah Spain, Rachael Tan, Yuki Okada, Soumya Raychaudhuri, Sophia Steer, Andrew P. Cope and Cathryn M. Lewis Department of Rheumatology, King’s College London, London, Department of Medical and Molecular Genetics, King’s College London, London, UK, Division of Genetics, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA, Department of Rheumatology, King’s College Hospital, London, UK

Background Socio-economic deprivation is known to be associated with an adverse prognosis in rheumatoid arthritis (RA); some of this may be due to differential interaction of individuals with their healthcare providers after symptom onset. Rheumatoid factor (RF) and anti-citrullinated peptide antibody (ACPA) status can precede clinical onset of RA by up to ten years and thus may provide a unique insight into factors affecting immunological events in the pre-clinical stage. In support of this, ACPA-positive and ACPA-negative RA have distinct genetic and environmental risk factors. Objectives To assess the association between area level socio-economic deprivation and the phenotype of RA, defined by RF and ACPA status, and to determine whether any observed association can be explained by smoking. Methods Logistic regression analysis of 6298 patients with RA, defined by American College of Rheumatology classification criteria modified for genetic studies. Analysis was stratified by cohort/recruitment centre. Socio-economic deprivation was measured using the Townsend index. Results Deprivation predicted RF but not ACPA positivity, independent of smoking. The odds ratios (OR) for trend across tertiles of deprivation, adjusted for smoking, gender, period of birth and cohort/recruitment centre, were: 1.14 (95% confidence interval (CI) 1.01 to 1.29) for RF, and 1.01 (95% CI 0.87 to 1.16) for ACPA. Even after adjusting for deprivation, smoking was strongly associated with ACPA positivity (OR 1.38, 95% CI 1.22 to 1.55). There was no evidence of any effect modification by the RA risk alleles ( HLA-DRB1 shared epitope and PTPN22 rs2476601) that are known to modify the effect of smoking on ACPA and RF positivity. Conclusions Amongst patients with RA, deprivation predicted RF positivity, but not ACPA positivity. The effect of deprivation did not appear to be explained by smoking. We avoided case-control response bias by performing a case-only analysis. Deprivation may be a marker for previously-unrecognised, potentially modifiable environmental influences on the immunological phenotype of RA. Furthermore, given the known associations of RF positivity with prognosis and response to treatment in RA, these findings have potential implications for resource allocation and healthcare delivery. Disclosure of Interest None Declared

Background Methotrexate (MTX) is the most commonly used disease modifying anti-rheumatic drug (DMARD) for the treatment of rheumatoid arthritis (RA). Methotrexate pneumonitis (MP) is a potentially fatal hypersensitivity reaction with a mortality rate of ∼20%, the risk being maximal in the first year of treatment. The incidence of MP is higher in patients with pre-existing lung disease, particularly interstitial lung disease (ILD). Early identification of these patients provides the opportunity to offer an alternative agent. Prior to commencing MTX the current British Society for Rheumatology guidelines advise a screening chest radiograph (CXR). CXR has a low sensitivity for detecting ILD and it has been suggested that carbon monoxide transfer factor (TLCO) is a more sensitive marker. The guideline of the Rheumatology department at King’s College Hospital is to request a pulmonary function test (PFT) as well as a CXR prior to commencing MTX in all RA patients. If the TLCO is abnormal a high-resolution computerised tomography scan (HRCT) is considered. Objectives To investigate whether screening with PFT and CXR identifies more patients with ILD than screening with CXR alone. Methods 107 MTX-naive RA patients aged 21–86 who had previously had CXR and PFT were identified from the hospital database. Those patients with an abnormal TLCO (defined as ≤79% in non-smokers and ≤69% in smokers) who had undergone HRCT were included. Where ILD was identified on HRCT, the CXR was reviewed for abnormalities. Results Of the 107 patients, 44 with normal TLCO were excluded and a further 23 patients were excluded as they had not had HRCT. Of the 40 remaining patients, ILD was identified in 12 (see Table) of whom 6 (50%) had a normal CXR. 9 (75%) patients had early RA, defined as within 3 years of symptom onset. Of the 6 patients with abnormal CXR, 5 had TLCO Conclusions Our results show that the combination of CXR and PFT detects more patients with RA ILD compared to CXR alone, particularly in less advanced respiratory disease. In this cohort of RA patients undergoing pre-MTX screening we identified 12 patients with ILD, a prevalence of 11%. 50% of these patients would not have been identified by screening with CXR alone. MP is a rare but potentially fatal side-effect of MTX treatment. It is well recognized that prognosis is significantly worse in RA patients with ILD. Therefore we suggest early screening with PFT to identify these patients, allowing appropriately tailored management. References Disclosure of Interest : None Declared

Background Improved characterisation of the risk factors for rheumatoid arthritis raises the possibility that they could be combined to identify individuals at high risk of disease in whom preventive strategies can be evaluated. Our aim was to develop a prediction model capable of identifying such individuals with sufficient accuracy to enable the assessment of preventive treatments. Methods Our prediction model combines odds ratios for 15 HLA-DRB1 alleles, 31 non-HLA single nucleotide polymorphisms (SNPs), and smoking status to classify an individual's risk of seropositive rheumatoid arthritis. Our novel modelling technique employs confidence intervals to classify disease risks using a computer-simulated population. We developed several models (HLA, HLA-10/20/31 SNP, HLA-smoking models) to evaluate the impact of different factors on prediction. The ability of each model to discriminate between rheumatoid arthritis and controls was evaluated in two European cohorts: the Wellcome Trust Case Control Consortium (WTCCC: 1542 cases, 1226 controls) and the UK Rheumatoid Arthritis Genetics Consortium (UKRAG: 2623 cases, 1503 controls). Findings HLA-DRB1 alleles conferred most prediction: the WTCCC HLA-only model classified 50% antibodies to citrullinated protein antigens (ACPA)-positive rheumatoid arthritis versus 17% controls as high risk and 60% controls versus 25% ACPA-positive rheumatoid arthritis as reduced risk. Adding smoking information improved prediction (p=0·00033); SNPs provided no significant benefits. The highest area under the curve was 0·81 (95% CI 0·78–0·85). Only a minority had substantially elevated risks of rheumatoid arthritis: 6·9% ACPA-positive cases and 0·31% controls in WTCCC had an odds ratio for rheumatoid arthritis of more than 20 when evaluated with the HLA-31 SNP model. Interpretation Combined information on HLA-DRB1 alleles and smoking provides informative risk prediction for rheumatoid arthritis. Since only a minority of individuals are at substantially elevated risks, modelling may be best focused in a-priori high-risk groups such as those with family histories of rheumatoid arthritis. Further work is needed to define risk factors with large effect sizes for incorporation within our modelling framework. Funding Arthritis Research UK.

Backgroundand objectives The female preponderance of rheumatoid arthritis (RA) implies that reproductive factors may play an important role in its pathogenesis. Although several studies have shown an inverse association between previous pregnancy and RA development this finding has not been consistently reproduced and the precise relationship remains uncertain. The authors therefore undertook a systematic review and meta-analysis of observational studies examining pregnancy as a risk factor for RA. Our primary aim was to establish if pregnancy is associated with the risk of RA. Our secondary aim was to evaluate if this risk varies by rheumatoid factor (RF)/anticyclic citrullinated peptide antibody (ACPA) status. Materials and methods Search strategy: the authors searched Medline/EMBASE (1947 November 2011) using the search terms ‘rheumatoid arthritis.mp’ or ‘arthritis, rheumatoid/’ and ‘pregnancy.mp’ or ‘pregnancy/’ (limited to ‘humans’). The Scottish Intercollegiate Guidelines Network observational study filter was applied. Included manuscript bibliographies were reviewed. Inclusion Criteria: 1) case-control/cohort studies; 2) examining relationships between pregnancy and RA risk; 3) reporting effect size data as OR/RR with 95% CIs in parous versus nulliparous females (or providing crude data allowing their calculation). Statistics: Due to the low prevalence of RA, ORs/RRs were used interchangeably. Due to heterogeneity a random effects model was used to estimate summary ORs/RRs. Crude and adjusted ORs/RRs were evaluated separately. Results 248 citations were identified. 14 studies were included – 10 case-control (evaluating 1967 cases and 6113 controls) and four cohort studies (evaluating 8118 incident RA cases from 2 308 533 individuals). Crude and adjusted ORs/RRs were available for eight studies; three cohort studies reported adjusted and three case-control reported crude ORs/RRs only. Previous pregnancy was inversely associated with RA. The unadjusted summary OR for RA in parous versus nulliparous women was 0.76 (0.63–0.91). The adjusted summary OR for RA was also significant at 0.81 (0.68–0.96). Only a single study stratified risk by RF status- no significant relationship was identified with either subset. No studies evaluated risk by ACPA status. Conclusions Our systematic review shows an inverse relationship between previous pregnancy and RA. Although this indicates a likely protective effect of parity on the risk of RA development caution is required because the largest risks were observed in case-control studies, which are open to recall bias and cannot prove causality. The authors consider that further prospective cohort studies are required, evaluating cases by ACPA status, to better discern what risk factors are important in RA subset pathogenesis.