P. de Pablo

Performance of the 2010 ACR/EULAR criteria for rheumatoid arthritis: comparison with 1987 ACR criteria in a very early synovitis cohort

Objective Early identification of patients with rheumatoid arthritis (RA) is essential to allow the prompt institution of therapy. The 2010 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) classification criteria, which replace the 1987 classification criteria, have been developed to facilitate such identification in patients with newly presenting inflammatory arthritis. This study therefore assesses the performance of these new criteria in patients with early synovitis. Methods Data were analysed from patients with synovitis seen within 3 months of the onset of inflammatory arthritis. Patients were followed for 18 months to determine outcomes, and data on the cumulative fulfilment of 2010 and 1987 criteria and therapy were recorded. Results 265 patients were included in the study. 60 had alternative diagnoses at baseline. Of the remaining 205 patients, 20% fulfilled both 1987 and 2010 criteria, 3% fulfilled only 1987 criteria and 22% fulfilled only 2010 criteria at baseline. The 2010 criteria, when applied at baseline, detected more patients who eventually required disease-modifying antirheumatic drugs (DMARD) (65 (62%) vs 40 (38%); p<0.001), especially methotrexate (50 (68%) vs 31 (42%); p<0.01), within the first 18 months. However, more patients whose disease eventually resolved without ever requiring DMARD were classified at baseline as RA according to the 2010 criteria than with the 1987 criteria (16 (8%) vs 5 (2%); p=0.01). Conclusion The 2010 ACR/EULAR criteria allow more rapid identification of patients requiring methotrexate compared with the 1987 ACR criteria when applied at baseline. However, overdiagnosis is an important issue to consider if these criteria are to be used in very early disease.

Cardiovascular risk factors in women with primary Sjögren's syndrome: United Kingdom primary Sjögren's syndrome registry results

To determine the prevalence of traditional cardiovascular risk factors using established definitions in a large cohort of clinically well‐characterized primary Sjögrens syndrome (SS) patients and to compare them to healthy controls.

OP0052 Use of ultrasound to predict persistence in patients with very early synovitis

Background Early identification of patients at risk of persistent as opposed to spontaneously resolving arthritis is essential to allow the prompt institution of therapy and to provide vital information from the patient’s perspective. Currently available prediction strategies for persistent disease include that developed by Visser et al1. The identification of biomarkers that can improve such prediction strategies is an important goal. We have previously shown that data from ultrasound joint assessment adds to the accuracy of the Leiden Rule for prediction of RA. Here we present data on the utility of ultrasound to predict persistence in a very early synovitis cohort. Objectives To evaluate musculoskeletal ultrasound (MSUS) detection of synovitis and erosions as a predictor of persistent disease in patients with very early synovitis. Methods 91 patients with clinically apparent synovitis of at least one joint and duration ≤3 months of any symptom attributable to inflammatory arthritis were followed prospectively for 18 months and underwent clinical, laboratory, radiographic and 38 joint ultrasound (MSUS) assessments at baseline. MSUS variables included power Doppler (PD) and greyscale (GS) defined on 0-3 categorical scales. Sensitivity and specificity for persistent disease (at 18 months of follow-up) were determined for MSUS variables. Logistic regression models were used to evaluate the predictive ability of MSUS over and above the Visser score. Results 35 (38%) patients had resolving disease, whilst 56 (62%) developed persistent disease (including both RA and non-RA phenotypes). Ultrasound demonstrated subclinical joint involvement in both patient groups for all joint regions assessed. However power Doppler (PD) and Greyscale (GS) median joint counts were all significantly higher in the patients with persistent disease compared with those with resolving disease (PD: 10 vs 3 joints, p<0.001 and GS: 14 vs 4 joints, p<0.001, respectively). 18 patients (32.1%) with persistent disease had erosions of hands or feet detectable at baseline by ultrasound, not present in any patients with resolving disease (p<0.001). Global ultrasound joint counts and several individual MSUS variables, particularly at the MCP and PIP joints, were associated with persistence independently of the Visser score. Logistic regression analysis showed that compared to the Visser score alone, the Visser score with added MSUS variables GS≥2 at the MCP joints and PD≥2 at the PIP joints improves area under the curve values significantly (0.816 and 0.912 respectively, p<0.01). Conclusions Subclinical disease detected by ultrasound is more common in persistent than resolving disease. We have identified a number of ultrasound variables that provide important prognostic information on the development of persistent disease and have shown that useful data can be gathered from the assessment of a limited number of joints. Larger studies are required to fully evaluate the optimal weightings of these variables for use in a persistence algorithm. References [1] Visser H, le Cessie S, Vos K, Breedveld FC, Hazes JM. How to diagnose rheumatoid arthritis early: a prediction model for persistent (erosive) arthritis. Arthritis Rheum 46(2):357-65. Disclosure of Interest A. Filer Grant/Research support from: Cellzome and Pfizer, M. Cader: None Declared, A. Abhishek: None Declared, G. Allen: None Declared, C. Buckley Grant/Research support from: Wyeth, Cellzome, UCB and Pfizer, P. de Pablo: None Declared, K. Raza Grant/Research support from: Wyeth, Cellzome, UCB and Pfizer

AB0603 Periodontal Disease is Common in Patients with Systemic Lupus Erythemathosus

Background Periodontal disease is a common chronic inflammatory disease that has been associated with rheumatoid arthritis and a potential causal role has been suggested. However, data on the prevalence of periodontal disease in patients with systemic lupus erythematosus (SLE) are scarce. Objectives To investigate the prevalence of periodontal disease in patients with systemic lupus erythematosus and compare it to that of the general population. Methods We examined the periodontal status in dentate patients with SLE who met the ACR criteria for SLE. Mild periodontitis was defined as having at least one periodontal probing depth of 4+mm. Severe periodontitis was defined as having at least one periodontal probing depth of 6+mm. We compared the prevalence of periodontal disease in SLE patients with that of a geographically matched dentate sub-sample of the Adult Dental Health Survey (ADHS), West Midlands, a representative population survey in the UK (reference group). Age-standardized prevalence estimates were calculated and logistic regression was used to evaluate the association between SLE and periodontal disease adjusting for age and sex. Results We examined a total of 105 individuals with SLE, with a mean age of 45.6 years (IQR 36-56), of whom 98 (92%) were women. The reference group included 484 participants, with a mean age of 48.9 years (IQR 36-63), of whom 271 (56%) were women. The age-standardised prevalence of periodontitis was 85% (95% CI: 79% to 92%) in SLE patients, compared with 55% (95% CI: 51% to 60%) in the general West Midlands population. After adjustments for age and sex, patients with SLE were significantly more likely to have periodontitis than ADHS participants (OR 7.25, 95% CI 3.84 to 13.68). Results were similar when analyses were restricted to women only (OR 7.51, 95% CI: 3.85 to 14.64). The age-standardised prevalence of severe periodontitis was 11% (95% CI: 5% to 18%) in patients with SLE and 11% (95% CI: 8% to 14%) in the West Midlands population. No significant association of SLE with severe periodontitis was observed (OR 1.15, 95% CI: 0.56 to 2.36). Conclusions Our data suggests that periodontal disease is more common among individuals with SLE compared to a representative geographically matched sample. However, the prevalence of severe periodontal disease is similar between SLE and the general population. Further studies are necessary to confirm the possible association between periodontitis and SLE. Disclosure of Interest None declared

A1.5 Smoking is a risk factor for ACPA prior to onset of symptoms of rheumatoid arthritis in a cohort from southern europe.

Background and Objectives Rheumatoid arthritis (RA) is characterised by antibodies to citrullinated proteins (ACPA) which may be present several years before development of clinical symptoms. Smoking is a known risk factor for the development of RA, but data is scarce on the relationship of smoking with specific subsets of ACPA in the years before disease onset. In this study we examined the immune response to citrullinated antigens and a detailed smoking history, in a nested case-control study of subjects enrolled in the European Prospective Investigation into Cancer (EPIC) project who later developed RA. Materials and Methods The study sample included 412 participants from EPIC centres in Italy and Spain. Serum from 103 individuals who would eventually develop RA (pre-RA cases) were compared with three age-, sex- and centre-matched controls (n = 309). Antibodies to CCP, citrullinated-α-enolase peptide-1 (CEP-1; CKIHACitEIFDSCitGNPTVEC), citrullinated-fibrinogen (cFIB; CNEEGFFSACitGHRPLDKKC) and citrullinated-vimentin (cVIM; CVYATCitSSAVCitLCitSSVPC) were analysed by ELISA with positivity defined by 98th percentile of the controls. Results The median time to diagnosis in the pre-RA cases was 7 years (1.7–15.8 years). The frequency of positive antibodies (cases vs. controls) were: anti-CCP2 (20%; p < 0.001), anti-cFIB (18%; p < 0.001), anti-CEP-1 (15%; p < 0.001), and anti-cVIM (6%; p < 0.006). All of the antibodies increased in frequency closer to diagnosis and with no specificity being particularly prominent in very early presymptomatic autoimmunity. The frequency of ever smoking was higher amongst pre-RA cases compared with controls (59% vs. 47%, p = 0.02). Pre-RA cases who smoked had higher levels of ACPA by all measures, which reached statistical significance when comparing former smokers to other groups. Pre-RA former smokers were 2.5 times more likely to develop RA (OR 2.50, 95% CI: 1.28, 4.89; p = 0.007) and were four times more likely to have positive anti-CEP-1 (OR 4.06, 95% CI 1.02, 16.2) than pre-RA never smokers. Conclusions This is the first study of Pre-RA from a Southern European population in which we show that smoking is a risk factor not only for RA but for the development of presymptomatic autoimmunity, with citrullinated enolase being prominent. This strengthens the hypothesis that smoking is of aetiological importance in the very early stages of generating the autoantibodies that ultimately drive the disease.

SAT0107 Ultrasound defined tenosynovitis improves the prediction of rheumatoid arthritis and persistent disease in patients with very early synovitis

Background Tenosynovitis (TS) is a common manifestation of rheumatoid arthritis and postulated to be an early marker of disease but requires imaging to reliably detect its presence. The prevalence of tenosynovitis in patients with very early arthritis is unknown and there have been no studies on tenosynovitis as a predictor of the development of either rheumatoid arthritis (RA) or persistent disease. Objectives 1) to establish the prevalence of tenosynovitis assessed by ultrasound in patients with unselected very early arthritis, 2) to explore whether the presence of tenosynovitis defined by ultrasound improves the prediction of RA or persistence compared with corresponding predictive algorithms, i.e. the Leiden and Visser score. Methods We included 91 patients with clinically apparent synovitis of at least one joint and duration ≤3 months of any symptom attributable to inflammatory arthritis. Patients were followed prospectively for 18 months and underwent clinical, laboratory, radiographic and ultrasound assessments at baseline. We used ultrasound of hand, wrist, shoulder and ankle tendons to establish the prevalence of tenosynovitis detected by greyscale and power Doppler modalities. Ultrasound tenosynovitis variables were then analysed for their ability to improve sensitivity and specificity by calculating area under the curve (AUC) values, and comparing with predictive algorithms: the Leiden score for RA and the Visser score for persistent disease. Results Out of the 91 patients, 39 patients developed very early rheumatoid arthritis (VERA), 17 developed very early non-rheumatoid arthritis (VENRA) and 35 had resolving disease at follow-up. All patient groups had evidence of tenosynovitis at baseline (92%, 71%, and 71% respectively). Symmetrical PD involvement of wrist extensor tendons was more prevalent in VERA patients compared with patients with VENRA (36% vs. 6%, p<0.05) and resolving disease (11%) but there were no other significant differences in tenosynovitis distribution between VERA and VENRA groups. Tenosynovitis variables did not improve Leiden score AUC values for the prediction of RA. In contrast, tenosynovitis variables including wrist flexor and hand extensor tenosynovitis had good specificity (both 94%) for persistent disease. Tenosynovitis of the hands was more common among patients with persistent disease (VERA and VENRA) compared with patients with resolving disease (63% vs. 17%, p<0.001). Compared to the Visser score alone, presence of hand tendon or wrist flexor tendon PD involvement improved area under the curve values for the prediction of persistent arthritis, independent of the Visser score (0.816 and 0.878, p<0.05). However ultrasound assessment of tenosynovitis conferred no additional benefit and was less useful than the additional predictive value gained from ultrasound greyscale or PD scanning for joint involvement. Conclusions Tenosynovitis is common in very early arthritis and symmetrical wrist extensor tendinitis is significantly more common in very early RA. We have identified tenosynovitis ultrasound variables that are predictive for persistent disease. However these have inferior predictive value compared to ultrasound assessment of joints alone in very early disease. Disclosure of Interest A. Filer Grant/Research support from: Cellzome and Pfizer, M. Cader: None Declared, A. Abhishek: None Declared, G. Allen: None Declared, C. Buckley Grant/Research support from: Wyeth, Cellzome, UCB and Pfizer, P. de Pablo: None Declared, K. Raza Grant/Research support from: Wyeth, Cellzome, UCB and Pfizer

AB0279 Incidence of diabetes and effect of etanercept and adalimumab on hba1c over 1 year: data from a randomised trial in patients with rheumatoid arthritis

Background Inflammation such as that which occurs in rheumatoid arthritis (RA) is associated with insulin resistance and risk of diabetes mellitus (DM). Some DMARDs including TNF inhibitors (TNFi) may improve insulin resistance and DM risk. However, it is unknown whether TNFi improve HbA1c in patients with RA with or without DM. Data on HbA1c was collected in a randomised trial comparing drug continuation rates for etanercept and adalimumab (1). Objectives To estimate the incidence of DM from this data and study the impact of therapy on HbA1c. Methods Participants with active RA, who had previously failed to respond to 2 non-biologic DMARDs including methotrexate, were randomised to etanercept or adalimumab and followed 3-monthly over 1 year. Data collected included co-morbidities, clinical and laboratory parameters, and medications at each visit. The primary endpoint was newly recorded diabetes defined as HbA1c ≥48mmol/mol at any time point. Predictors of HbA1c and HbA1c change were determined with univariate and multivariate analyses. Results Of the 125 patients with active RA randomised to etanercept or adalimumab, 6 (4.8%) were known diabetics and 88% were RF/ACPA positive. Of the 119 without DM, 7 (5.9%) were diagnosed with DM (HbA1c ≥48mmol/mol) at baseline. 73 participants (73% female) completed 1 year of TNFi therapy: mean age 54 yrs (SD±12), mean BMI 27.8, mean HbA1c 38 mmol/mol. Of these, 4 (5%) patients had DM at baseline. A majority of patients were on methotrexate (67%) and 33% on prednisolone. Baseline characteristics were similar for patients’ allocated to adalimumab (52%) or etanercept (48%), except more patients on etanercept were on prednisolone (49% vs. 18%; p=0.006); and more patients on adalimumab were on hydroxycloroquine (24% vs. 3%; p=0.01). After excluding those with known DM at baseline, among those completing one year of TNFi (n=69), 3 (4.4%) patients had an HbA1c ≥48 mmol/mol at baseline,1 (1.5%) at 3 months,1 (1.5%) at 6 months, and 2 (2.9%) at 12 months of follow-up. 2 (3%)cases had aHbA1c ≥48 mmol/mol at 2 follow-up visits. The incidence of DM was 29 new cases per 1000-person years (95% CI 3.51-105). Those on adalimumab tended to have higher levels of HbA1c than those on etanercept but the differences between groups at each time point were non-significant. However, there was a significant rise in HbA1c levels after 1 year of adalimumab therapy (37.27 mmol/mol and 38.80 mmol/mol; p=0.01). Etanercept therapy did not influence HbA1c levels over time. Conclusions Incidence of diabetes in patients entering a randomised trial of etanercept and adalimumab was considerably higher than other recent data. Treatment with a TNFi did not improve HbA1c levels with either agent in diabetics and non-diabetics. After excluding those with diabetes, those on adalimumab had higher mean HbA1c levels after 1 year of therapy. References BMJ Open 2012;2:e001395. Disclosure of Interest None Declared

The role of ultrasound-defined tenosynovitis and synovitis in the prediction of rheumatoid arthritis development.

Abstract Objectives Tenosynovitis (TS) is common in early arthritis. However, the value of US-defined TS in predicting RA development is unclear. We assessed the predictive utility of US-defined TS alongside US-defined synovitis and clinical and serological variables in a prospective cohort of early arthritis patients. Methods One hundred and seven patients with clinically apparent synovitis of one or more joint and symptom duration ⩽3 months underwent baseline clinical, laboratory and US assessment of 19 bilateral joint sites and 16 bilateral tendon compartments. Diagnostic outcome was determined after 18 months, applying the 2010 ACR/EULAR classification criteria for RA. The predictive values of US-defined TS for persistent RA were compared with those of US-defined synovitis, clinical and serological variables. Results A total of 4066 US joint sites and 3424 US tendon compartments were included in the analysis. Forty-six patients developed persistent RA, 17 patients developed non-RA persistent disease and 44 patients had resolving disease at follow-up. US-defined TS in at least one tendon compartment at baseline was common in all groups (RA 85%, non-RA persistent disease 71% and resolving 70%). On multi-variate analysis, US-defined digit flexor TS provided independent predictive data over and above the presence of ACPA and US-defined joint synovitis. Conclusion US-defined digit flexor TS provided independent predictive data for persistent RA development in patients with early arthritis. The predictive utility of this tendon site should be further assessed in a larger cohort; investigators designing imaging-based predictive algorithms for RA development should include this tendon component as a candidate variable.

AB0290 Lower educational levels are associated with a higher risk of rheumatoid arthritis in a southern european nested case-control study

Objectives To investigate the association between socioeconomic status (SES) on an individual level and incident RA Methods EPIC is a multicentre, pan-European prospective cohort study of apparently healthy populations. We undertook a nested case-control study to investigate risk factors for RA, by identifying incident RA cases (pre-RA) and matched controls amongst subjects enrolled in four EPIC cohorts in Italy and Spain. The lifestyle, environmental exposure, anthropometric information and blood samples were collected at baseline. Confirmed pre-RA cases were matched with controls by age, sex, centre, and date, time and fasting status at blood collection. The exposure was SES as measured by level of educational attainment categorised as university (referent), secondary school/technical/professional school, primary school completed, and none. The primary outcome was incident RA. Conditional logistic regression (CLR) analysis was adjusted for ACPA seropositivity, smoking status, and presence of shared epitope (SE). A further model also adjusted for other potential confounders, including body mass index (BMI), waist circumference, physical activity, and alcohol intake. Results The study sample included 398 individuals of which 99 individuals went on to subsequently develop RA. In this analysis, time to diagnosis (defined as time between date of blood sample and date of diagnosis), was 6.71 years (SD 3.43). A significant positive association was observed with level of educational attainment and RA incidence (secondary/technical vs university: OR 5.60, 95% CI 1.59–19.7, primary school vs university: OR 5.06, 95% CI 1.45–17.6, no education vs university: 7.11, 95% CI 1.37–36.8; p for trend 0.02) independent of ACPA seropositivity, SE and smoking). A significant positive association between level of educational attainment and RA incidence was confirmed in the fully adjusted model (secondary/technical vs university: OR 5.52, 95% CI 1.53–19.9, primary school vs university: OR 4.87, 95% CI 1.38–17.1, no education vs university: OR 6.48, 95% CI 1.21–34.6; p for trend 0.02). Conclusions Lower educational levels were independently associated with higher risk of incident RA in this European Mediterranean population. Disclosure of Interest None declared

ULTRASOUND-DEFINED TENOSYNOVITIS PREDICTS RA IN PATIENTS WITH RECENT-ONSET INFLAMMATORY ARTHRITIS

Background and objective Tenosynovitis is common in early arthritis and the OMERACT Ultrasound Task Force recommended that US is a reproducible tool for evaluating tenosynovitis (TS) in RA. However, the value of US-defined tenosynovitis (TS) in the prediction of RA development is unclear. We assessed the ability of US-defined TS to predict the development of persistent RA in a prospective cohort of patients with early arthritis. Methods 107 patients with clinically apparent synovitis of at least one joint and symptom duration ≤3 months underwent baseline clinical, laboratory and tendon US assessments and the presence of grey scale and Power Doppler TS at 16 bilateral tendon compartments was determined [bilateral fingers (flexor compartments), wrists (extensor and flexor compartments), shoulders (biceps tendon), ankles (anterior extensors, peroneals, posterior tibialis)]. Outcome was determined after 18 months, applying the 2010 ACR/EULAR classification criteria for RA. The predictive values of US-defined TS for persistent RA were compared with clinical and serological variables. Results A total of 3424 tendon compartments were included in the analysis. 43 patients developed persistent RA (RA), 20 patients developed non-RA persistent disease (NRAP) and 44 patients had resolving disease at follow-up. All groups had evidence of TS in at least one tendon compartment at baseline (RA 85%, NRAP 71%, and Resolving 71%). In multivariate logistic regression, extensor carpi ulnaris (ECU) and digit flexor tendon involvement were predictive of persistent RA and provided additional predictive data over and above the presence of high levels of autoantibodies and clinical involvement of more than 10 joints [ECU or digit flexor TS (OR = 5.25, p = 0.001), >10 clinically tender or swollen joints (OR = 7.96, p < 0.001), RF or ACPA high-positivity (OR = 7.31, p = 0.001); AUC = 0.86, Nagelkerke’s R2 = 0.499]. Conclusion This is the first study to illustrate that US-detected TS is predictive of persistent RA in patients with early arthritis. ECU and digit flexor tendon scanning provides optimal predictive data over and above clinical and serological variables.