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BackgroundTo comparatively investigate the differential effect of second-line tumour necrosis factor inhibitors (TNFis) versus other biological agents on cardiovascular disease (CVD) risk-associated biomarkers in patients with rheumatoid arthritis (RA).MethodsWe evaluated the serum levels of lipoprotein-associated apoproteins ApoA1 and ApoB100 and lipoprotein(a) (Lp(a)) and the leptin/adiponectin ratio (LAR) as an insulin resistance proxy in patients with RA from the Rotation Or Change (ROC) trial treated with either a second-line TNFi or another biologic (tocilizumab (TCZ), rituximab or abatacept) at baseline and week 24. We compared the changes in biomarker levels in each group and according to the EULAR response.ResultsOf the 300 patients enrolled in the ROC trial, 203 were included in the study, including 96 in the second-line TNFi group and 107 in the other biological group. The measured biomarkers did not deteriorate between baseline and week 24 regardless of the group. A greater improvement in the LAR was noted in the other biological group (median (IQR) −0.12 ng/µg (−0.58 to 0.31) vs 0.04 (−0.19 to 0.43), p=0.033), and a greater improvement in the Lp(a) level was observed following treatment with TCZ than with a TNFi (−0.05 g/L (−0.11 to −0.01) vs −0.01 g/L (−0.02 to 0.01), pConclusionsTNFis and non-TNFis were neutral on improved CVD risk-associated biomarkers in patients with RA insufficiently controlled by TNFis. TCZ could be associated with a better improvement concerning Lp(a) and LAR than TNFis. This improvement could be related to a good therapeutic response, thereby supporting the need of good control of RA.Trial registration numberClinicalTrials.gov Identifier NCT01000441, registered on 22 October 2009.

Background Several reports have found an association between gout and osteoarthritis (OA). Urate levels in OA synovial fluid has been shown to associate with both knee OA severity and production of proinflammatory cytokines. However, the impact of serum urate (SUA) levels on pain and disability or radiographic damages in patients with established knee or hip OA remains unknown Objectives To search for an association between SUA levels and OA severity and OA symptoms in a cross-sectional analysis of a large cohort of patients Methods Data are from 863 subjects with knee or hip OA from the KHOALA (Knee and Hip Osteo-Arthritis Long-Term Assessment) cohort. For each patient, SUA, CRPus, serum adipokines and lipids levels were assessed at inclusion. Baseline clinical data included the WOMAC (total, pain, stiffness and function) and the Harris, the IKS and Osteoarthritis Knee and Hip Quality of Life (OAKHQOL) scores. Associations between SUA levels and OA symptoms and disability was searched using uni and multivariate linear regression and associations between SUA levels and the presence of one or more radiographic OA with multivariate logistic regression. Results 863 patients (69.1% women) were included. Mean age was 61.9 (±8.5) years and mean BMI 29.4 (±6) kg/m2 . 87 (10.1%) patients had diabetes. OA involved uni- or bilateral knees in 653 patients and uni- or bilateral hip in 286 patients. Mean SUA levels was 340 μmol/l (range 110.0-910.0). Hyperuricemia (SUA >360 μmol/l) was observed in 305 (35.3%) patients. The level of uricemia was weakly correlated with BMI (r=0.23), insulinemia (r=0.273) and the triglycerides level (r=0.296). SUA levels did not significantly correlate with the WOMAC, the Harris, the IKS or the OAKHQOL scores in patients with either symptomatic knee or hip OA. In addition, SUA was not associated with the number of symptomatic knee or hip OA joints or radiographic knee or hip OA joints Conclusions In this large cohort of patients with knee or hip OA, SUA levels were not associated with OA symptoms, severity or radiographic damages. Such results do not exclude a prognostic value of SUA on OA progression. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.3864

Background Metabolic syndrome-related osteoarthritis (OA) is now considered as a peculiar subgroup of OA involving systemic factors as insulin resistance and adipokines. However, few studies searched for a relationship between serum adipokines and/or insulinemia and OA in a large group. Objectives To investigate whether insulinemia, the serum leptin/adiponectin (L/A) ratio (known to increase in insulin resistant states) 1 and individual serum adipokines may be independently associated with hip OA clinical symptoms in a OA population-based cohort study. Methods Subjects aged 40-75 years, with uni or bilateral symptomatic hip and/or knee OA (ACR criteria), Kellgren and Lawrence ≥2, were recruited in the multicenter KHOALA (Knee and Hip Osteo-Arthritis Long-Term Assessment) cohort 2 . Exclusively patients included for symptomatic hip OA were investigated here. Beyond demographic data, clinical evaluation of OA at inclusion was based on WOMAC score for pain, stiffness and function (higher values in more symptomatic patients) and on Osteoarthritis Knee and Hip Quality of Life (OAKHQOL) questionnaire (higher values in less symptomatic patients). A blood sample at inclusion was collected to assess adipokines (i.e. total and high molecular weight [HMW] adiponectin, leptin, visfatin), insulinemia as well as potential confounders (i.e., ultrasensitive CRP level, creatininemia, total cholesterol, triglycerides, apoA1 and ApoB100 levels). Multivariate linear regression models were used to determine whether insulinemia, serum adipokines or L/A ratio were associated with hip OA symptoms. Results 284 patients were included for uni- or bilateral symptomatic hip OA (66% female, mean age ± SD: 61.8±8.8 years, mean body mass index 27.6±4.9 kg/m 2 ). Serum visfatin, total adiponectin, HMW adiponectin, leptin, L/A ratio and insulinemia were 4.2±2.1 ng/mL, 6.6±3.7 μg/mL, 3.7±2.5 μg/mL, 22.8±25.4 ng/mL, 1.42±1.1 and 91.1±87.7 pmol/L, respectively, without significant difference between uni- and bilateral involvement. Multivariate analyses showed that the L/A ratio, but not each adipokine considered separately or insulinemia, was positively correlated with total WOMAC (β=3.1; p=0.002). This correlation was mainly due to the correlation with the function WOMAC subscore (β=3.3; p=0.002). Again, only the L/A ratio was independently correlated with OAKHQOL pain (β=-3.4; p=0.01) but not OAKHQOL physical activity. In addition, serum leptin level was independently correlated with OAKHQOL physical activity (β=-2.9; p=0.05). Conclusions In hip OA, a higher L/A ratio seems to be associated with a poorer clinical hip OA outcome, highlighting the association of insulin resistance with more severe hip OA symptoms. This association was independent of all confounders including BMI, age and other metabolic parameters, suggesting a potential direct impact of adipose tissue and related insulin resistance on OA. References FM Finucane et al Diabetologia 2009;52:2345–2349. F Guillemin et al Joint Bone Spine 2012;21:597-603. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.4731

Background Adipokines have recently emerged as pro-inflammatory mediators involved in the pathophysiology of rheumatoid arthritis (RA). Objectives To determine whether serum adipokine levels independently predicted early rapid radiographic disease progression (RRP) in early RA. Methods ELISA was used to assess baseline serum levels of total adiponectin, leptin and visfatin/NAMPT in the 632 patients from the French ESPOIR cohort who met the American College of Rheumatology-European League Against Rheumatism criteria for RA. We tested the association of serum adipokine levels and RRP defined as a change ≥ 5 in total Sharp-van der Heijde Score between inclusion and 1 year (ΔSHS≥5) corresponding to the destruction of one small joint (1) in univariate analysis and also after adjusting for all pertinent confounders (age, sex, body-mass-index, insulin resistance log(HOMA-IR), C-reactive protein level (logCRP), DAS28, log(HAQ score), rheumatoid factor and anti-CCP antibodies status, steroid use and radiographic evidence of RA damage at inclusion. Sensitivity versus the false positive frequency (1-specificity) for predicting radiographic disease progression with adiponectin levels was analysed by a receiver-operated characteristic (ROC) curve. The optimal cut-off point of adipokines level to identify patients with RRP was calculated using Youden index. Results In univariate analyse, there was a trend for association between serum level of adiponectin and RRP (odds ratio OR [95%confidence interval]=1.47 [0.98-2.20]; p=0.06). In multivariate model, serum adiponectin level was independently associated with ΔSHS≥5 (adjusted OR=2.0 [1.14-3.52], p=0.0165) (Table). Conversely, leptin level was associated with RRP only in univariate analyse (OR=0.73 [0.54-0.97]; p=0.03) and visfatin/NAMPT level displayed no association. Considering the ROC curve, the best serum adiponectin cut-off value level to predict ΔSHS ≥ 5 was 1.60 μg/mL (sensitivity=0.74 and specificity=0.73 and area under the ROC curve=0.76). Conclusions Serum adiponectin level is a simple and useful biomarker predicting early RRP in early RA independently of RA-confounding factors and metabolic status. Using the threshold of 1.6 μg/mL, patients with early RA at increased risk of early RRP can be identified. References Vastesaeger N et al. Rheumatology(Oxford) 2009,48:1114-21 Disclosure of Interest None Declared

Background Hepcidin is an interleukin 6-induced peptide hormone produced by the liver and involved in iron homeostasis and inflammation. Previous published studies have suggested that hepcidin could be a key biomarker of severity in rheumatoid arthritis (RA). Objectives We investigated whether serum hepcidin level may represent a novel surrogate biomarker of RA features, disease activity, or of structural progression. Methods Serum hepcidin level was assessed by enzyme immunoassay kit (Bachem, UK) in 791 patients from the French ESPOIR early arthritis cohort (at least 2 swollen joints for more than 6 weeks and less than 6 months) who met the 2010 EULAR-ACR criteria for RA (n=632) or had undifferentiated arthritis (UA) (n=159) at inclusion. We compared baseline hepcidin levels between RA and UA, searched for a cross-sectional association with the baseline clinical, immunological and radiological RA features, and determined, using univariate and multivariate analyses, whether log-transformed hepcidin level may predict the progression of X-ray alterations defined by an increase of the total Sharp/van der Heijde score ≥1. Results Mean (±SD) level of hepcidin was higher in RA than in UA patients (53.02±48.45 vs 39.63±39.87 ng/mL, p Conclusions Serum hepcidin level is elevated in RF/anti-CCP-positive RA patients and in erosive RA. Serum hepcidin increase reflects a higher disease activity and correlates with HAQ, suggesting a clinical relevance of its assessment beyond its link with the ESR. However, its measurement does not give additional information compared to the usual biomarkers of inflammation nor it predicts radiographic progression. Disclosure of Interest None Declared