E.-M. Koh

SAT0346 Anti-Drug Antibodies as A Predictor for the Discontinuation of Anti-TNF Agents in Patients with Spondyloarthrtis

Background Tumor necrosis factor (TNF) blocking agent has shown to be effective in patients with axial spondyloarthritis (SpA) including ankylosing spondylitis (AS) as up to 60-70%. However, the other 30-40% of patients fails to respond. This non-responsiveness to TNF blocking agent has been suggested as the result of the development of antibodies against it, anti-drug antibodies (ADA), which have been described well in patients with rheumatoid arthritis and Crohns disease. Objectives The aim is to assess whether ADA is related to the clinical efficacy in SpA patients on anti-TNF agents. Methods According to the Assessment of SpondyloArthritis international Society (ASAS) classification criteria for axial SpA, consecutive patients were recruited at a single tertiary hospital who received treatment with adalimumab (Ada) or infliximab (Ifx): 86 AS, 11 inflammatory bowel disease associated SpA, 3 psoriatic SpA and 2 undifferentiated SpA. Serum samples were collected at the enrolment for the drug and ADA levels, which were measured by ELISA. Disease activity was assessed by the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) at baseline (at the beginning of the current anti-TNF agents), at 3 month and then every 6 months. The reactivation of tuberculosis infections, side-effects or infusion reactions, and the cause for discontinuation of therapy were assessed prospectively. Results A total of 102 patients were studied (89.2% male; mean age at sampling 35.2±18.0 years; mean disease duration 11.3±7.9 years). HLA-B27 was positive in 65 of 76 patients (85.5%). Among 102 patients, 74 were treated with Ada and 28 with Ifx. Eighteen patients (17.6%) had switched from other kinds of anti-TNF agents including Ada, Ifx and etanercept. Latent tuberculosis (TB) infection was detected in 22 patients (21.6%) before starting anti-TNF agents and the treatment regimen with isoniazid and rifampin was commenced by a TB expert. ADA was demonstrated in 8 patients (7.8%) (5 of Ada and 3 of Ifx) and all of them were anti-TNF naïve patients. Patients who developed ADA had lower levels of the corresponding drugs (Ada level: 0.45±0.68 vs 4.42±2.12, p<0.0001; Ifx level 0.91±1.36 vs 3.38±2.24, p=0.076). At baseline, no differences in BASDAI were found in patients with or without ADA, and neither ESR nor CRP was different. The median period under prospective observation was 15 months (range 0 – 17, mean 12.7±7.8). ADA-positive patients had a significantly higher cumulative drug discontinuation rate due to inefficacy and adverse events (37.5% vs 6.4%, p=0.022). There was no reactivation of tuberculosis during anti-TNF treatment. Conclusions Our result suggests that in SpA patients the presence of ADA to current Ada or Ifx can predict the drug discontinuation in future due to inefficacy or adverse events. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.3465

AB0901 Clinical significance of urate deposition in tendon: a dual-energy ct study

Background Dual-energy computed tomography (DECT) is advanced imaging modality that shows the deposition of monosodium urate (MSU) crystal in tissue as a color signal. The MSU crystal deposit around the symptomatic joint is considered as positive finding, but the clinical significance of urate deposition around the tendon is still unclear. Objectives The aim of this study was to compare the clinical characteristics and DECT findings in people with MSU crystal deposition in the joints and people with urate deposition in the tendons. Methods DECT was performed in 71 patients who complained of recurrent painful swelling of the joints, and 35 of them showed MSU crystal deposition in the joints on DECT. Clinical manifestation and serum uric acid level data were collected. Results Most of the included patients were middle-aged (mean age 50 years, SD 15) and 67 patients (94%) were male. All patients who had MSU crystal deposition in joints on DECT had a history of typical gout attacks, and 29 patients (81%) had a history of gout attacks among patients with urate deposition only in tendons (p=0.011). The mean uric acid level of patients included in the study was as high as 7.5±2.2 mg/dL. In the highest uric acid level, the absolute value was higher in patients with urate deposition in joints, but there was no statistical significance. The correlation between the gout attack site and the urate deposit sites was 91% in patients with joint involvement, but only 6% in patients without joint involvement (p<0.001). There were 4 patients (11%) who showed gouty erosion without MSU crystal deposition in joints on DECT. Conclusions The MSU crystal deposition in the tendon was not correlated well with clinical features, suggesting that it is more likely to be associated with artifact or asymptomatic hyperuricemia. However, in some patients, MSU crystal deposition may be observed only in the tendon, even with gouty erosion. Therefore, careful interpretation of the DECT results is necessary. Disclosure of Interest None declared

FRI0685 The presence of rheumatoid factor is associated with lower bone mass in korean health screening male subjects without clinically apparent arthritis

Background Close relationship between the immune and skeletal systems has been recognized through the bone loss in rheumatoid arthritis (RA). Rheumatoid factor (RF) is present in approximately 70–80% of RA patients, which is an autoantibody directed against the Fc component of IgG and associated with osteoporosis and reduced bone mineral density (BMD) in RA. RF is also found nonspecifically in chronic inflammatory condition such as sarcoidosis, hepatitis B or C, and tuberculosis. However, the influence of RF to bone loss is scarcely known in subjects without any specific medical problem. Objectives This cross-sectional study aimed to investigate the association between the presence of RF and BMD in Korean healthy male subjects without any history of joint disease. Methods Of the 84,344 males who had undergone a comprehensive health checkup program in 2012, 1,390 healthy subjects were recruited, whose BMD and RF results were available. Subjects with history of diabetes, kidney disease, thyroid disease, and malignancy, and taking medicine regarding these diseases, osteoporosis, and arthritis were excluded based on self-reported questionnaire. The RF titer ≥20 IU/ml was considered positive. BMD was categorized into 3 groups based on T-score; normal (T-score ≥ -1.0), osteopenia (-1.0 > T-score > -2.5) and osteoporosis (T-score ≤ -2.5). The association between the presence of RF and BMD was assessed by multiple linear regression analysis. Results Of 1,390 males, the mean age was 52.8±10.9 years (range, 22 – 83) and RF was positive in 64 subjects (4.6%). Demographics including smoking history, alcohol consumption, the frequency of vigorous exercise and body mass index (BMI), and laboratory data were not different between RF-positive and –negative subjects except hepatitis B surface antigen, which was more frequently seen in RF-positive subjects (15.6% vs. 4.3%, p =0.001). Low bone mass (osteopenia and osteoporosis) of lumbar spine was more prevalent in subjects aged 50 or more compared with those younger than 50 years (28.0% vs. 10.7%, p <0.001) while no differences of femur neck and total hip. RF-positive subjects had significantly lower BMD compared to RF-negative subjects in lumbar spine (1.10±0.18 g/cm2vs. 1.17±0.16 g/cm2, p =0.002) but neither in femur neck nor total hip. In subjects with higher titer RF (≥40 IU/ml), the mean BMD of lumbar spine was significantly decreased than those with lower titer RF (one-way ANOVA, F(3, 1190) =3.527, p =0.015). After adjusting for multiple confounders such as age, BMI, glomerular filtration rate, serum concentration of calcium, phosphorus, and uric acid, and lifestyle factors (drinking, smoking, and physical exercise), RF positivity was negatively associated with BMD at lumbar spine (B = -0.055 and SE =0.027, p =0.039). Conclusions Our results provide epidemiological evidence that the presence of RF could have an unfavorable impact on bone density in apparently healthy male subjects. Additional studies to elucidate the osteoimmunological mechanism of RF are warranted. Disclosure of Interest None declared

FRI0422 Estrogen attenuates the disease activity of spondyloarthritis in skg mice

Background Ankylosing spondylitis is a male-predominant disease, and the male gender is also associated with more severe radiographic damage. Estrogen modulates immune-related processes such as T cell differentiation and cytokine production. Objectives This study aimed to evaluate the role of estrogen in the disease activity of spondyloarthritis (SpA). The effect of estrogen on the inflammatory cytokines was evaluated. Methods The effects of estrogen on the development of arthritis were evaluated by performing an ovariectomy and E2 pellet implantation in the zymosan-treated SKG mouse. Clinical arthritis scores were measured and PET-CT was performed to quantify joint inflammation. Total RNA was extracted from the hindpaws and forepaws and the expression of TNFα, IL-6, IFNγ, IL-4, IL-17A, IL-23, Dkk1, and SOST was measured by QuantiGene 2.0 plex assay. Results Zymosan exposure triggered SpA-like diseases in SKG mice, including peripheral arthritis, spondylitis, dactylitis, enteritis, and psoriatic skin lesions. E2-treated mice showed remarkable suppression of arthritis clinically and little infiltration of inflammatory cells in the Achilles tendon and intervertebral disc. 18F-FDG uptake was significantly lower in the E2-treated mice. The expression of TNFα, IFNγ, IL-17A, Dkk1, and SOST was significantly reduced in E2-treated mice compared with sham and ovariectomized mice. Conclusions Estrogen suppressed arthritis development in SpA model of SKG mouse. Results of the study suggest that estrogen may have an anti-inflammatory effect on the disease activity of SpA. Disclosure of Interest None declared

FRI0331 Identification and validation of potential metabolomic biomarkers for reliable diagnosis of behcet's disease using gas chromatography with time-of-flight mass spectrometry

Background Although many diagnostic criteria have been developed and revised by experts in the field, diagnosing Behcets disease (BD) is still complicated and challenging. Metabolomic studies can lead to a better understanding of pathophysiological processes and may uncover new diagnostic markers for classification of disease subgroups and assessment of disease activity in rheumatic diseases. No metabolomic studies on serum have been attempted to improve the diagnosis and to identify potential biomarkers of BD. Objectives The purposes of this study were to investigate distinctive metabolic changes in serum samples of BD patients and to identify metabolic candidate biomarkers for reliable diagnosis of BD using the metabolomics platform. Methods Metabolomic profiling of 90 serum samples from 45 BD patients and 45 healthy controls (HC) was performed via gas chromatography with time-of-flight mass spectrometry (GC/TOF-MS) with multivariate statistical analyses. Thirty-five patients with BD and age- and sex-matched 35 HCs were randomly selected to form the discovery set, and the validation set is composed of 10 patients with BD and 10 HCs. Results We identified a total of 104 metabolites in the serum samples of the discovery set. To maximise the discrimination between groups BD and HCs, we applied supervised partial least squared-discrimination analysis (PLS-DA). A PLS-DA score plot of the discovery set indicated that the cluster of BD patients is well separated from HC clusters in component 1. The variation values of the PLS-DA model are R2X of 0.246, R2Y of 0.913, and Q2 of 0.852, respectively, indicating strong explanation and prediction capabilities of the PLS-DA model. The PLS-DA models did not show clear and consistent discrimination between groups according to drug administration, indicating that drugs used in patients with BD had a negligible effect on the distinct metabolic profiles discriminating BD patients from HCs. A panel of five metabolic biomarkers, namely, decanoic acid, fructose, tagatose, linoleic acid, and oleic acid were selected based on their variable importance on projection values and adequately validated as putative biomarkers of BD (sensitivity 100%, specificity 97.1%, area under the curve 0.993) in the discovery set and validation set. Principal component analysis showed clear discrimination of BD and HC groups by the five metabolic biomarkers in the validation set. Conclusions This is the first report on detection of a characteristic metabolic profile of BD and identifying and validating potential metabolite biomarkers in serum from BD patients using GC/TOF-MS. Further studies including a larger number of patients with BD would be warranted to validate the metabolite profiles for clinical use and to ascertain the feasibility of metabolomic analysis in BD. Disclosure of Interest None declared

THU0516 Serum Uric Acid Is Positively Associated with Pulmonary Function in Korean Health Screening Examinees: A Cross-Sectional Study

Background Serum uric acid (SUA) is an end product from the action of xanthine oxidase on purine or purine-containing compounds. Recently, much attention has been paid to the role of uric acid in disease modification. A recent study supports the view that hyperuricemia may be an independent risk factor for impaired pulmonary function in the general population. On the other hand, in view of its antioxidant properties, uric acid potentially has important beneficial effects within the respiratory system. The double-edged characteristics of SUA and mixed results from previous studies have complicated determination of whether SUA plays a pulmonary-protective or pulmonary-destructive role. Objectives The aim of this study was to determine whether level of SUA, a potent antioxidant, is linked to pulmonary function in health screening examinees without overt clinical disease. Methods We performed a cross-sectional study on 69,928 Koreans without overt medical conditions who underwent a health examination in 2010. Results A total of 30,572 male (43.7%) and 39,356 female eligible subjects were enrolled in our study. The overall prevalence of hyperuricemia among Korean health screening examinees was 25.5% in males and 8.5% in females. The median age of subjects was 40 (range 35–46) years. Increasing age was positively associated with SUA level. In sex-stratified analyses of SUA level, mean SUA level was positively associated with a quartile increase in FVC% and FEV1% in both genders (P <0.001). There were also a significant positive correlation between SUA level and spirometric measures (FEV1% or FVC%) in both genders (FVC%, r =0.361; FEV1% r =0.314 in men and FVC%, r =0.413; FEV1%, r =0.382 in women). Multiple regression analysis was performed to assess whether FEV1% and FVC% were independently associated with the prevalence of hyperuricemia. The adjusted ORs for hyperuricemia comparing quartiles 2, 3, and 4 to quartile 1 (the reference group, highest quartile) of FVC% in men were 0.876 (95% CI, 0.809–0.949), 0.631 (0.574–0.695), and 0.311 (0.278–0.349), respectively. The adjusted ORs for hyperuricemia comparing quartiles 2, 3, and 4 to quartile 1 of FEV1% in men were 0.791 (95% CI, 0.729–0.859), 0.565 (0.513–0.623), and 0.302 (0.270–0.337), respectively (p for trend <0.001). Similarly, the adjusted ORs of hyperuricemia in women decreased significantly across quartiles 2 to 4 of FEV1% and FVC % compared with the highest quartile as the reference group (P for trend <0.001). Conclusions SUA was positively associated with FVC% and FEV1% in a healthy Korean population. This finding has important implications for the hypothesis that hyperuricemia might have a favorable effect on lung function. Longitudinal follow-up studies and prospective interventional studies are required to confirm this positive association between SUA and lung function. Disclosure of Interest None declared

AB0273 Disease Characteristics and Change of Arthritis Activity According To Treatment in Hepatitis B Surface Antigen Positive Rheumatoid Arthritis Patients

Background Rheumatoid arthritis (RA) treatment may differ according to hepatitis B state and consequently bring about different outcome of arthritis. Only a small number of studies have addressed the differences in disease characteristics and treatment patterns of RA in relation to hepatitis B state. However, it has not yet been elucidated whether hepatitis B affects treatment outcome such as disease activity. Objectives We investigated possible differences in change of arthritis activity between RA patients according to concomitant hepatitis B virus (HBV) infection. Methods A retrospective analysis of 40 hepatitis B surface antigen (HBsAg)-positive RA patients and 112 HBsAg-negative RA patients was conducted. The longitudinal relationship between HBsAg-positivity and RA activity/medication use was analyzed using generalized estimating equations in regression models. Results There were no significant differences in group for baseline characteristics. In regression analysis, RA activity-related outcomes showed follow-up time-dependent improvement during study period. We observed significant interaction between time and HBsAg-positivity for disease activity score in 28 joints with 3 variables (DAS28–3; P =0.026), that means decreases in DAS28–3 with time influenced by HBsAg-positivity. But this interaction did not remain significant after adjustment. For tender joints, erythrocyte sedimentation rate, and C-reactive protein levels, there were no interaction between time and HBsAg-positivity, while swollen joints showed significant interaction (P =0.017). The time-association and group differences were not observed in alanine aminotransferase (ALT) level. Over all visits, HBsAg-positive patients were less likely to receive methotrexate (OR 0.09 [95% CI 0.04–0.19], P <0.0001) and more likely to receive sulfasalazine (OR 3.67 [95% CI 1.94–6.95], P <0.0001). In HBsAg-positive RA patients, initial hepatitis B state was related to use of DMARDs, especially methotrexate (P =0.040). Hepatitis reactivation occurred in 4 patients (10%) in HBsAg-positive RA patients. Among the patients who experienced HBV reactivation, only one patient had received previous antiviral treatment at baseline, but the patient exhibited lower adherence to drug. All patients who experienced HBV reactivation showed positive HBV DNA at baseline. There were no cases of hepatic failure or death. Conclusions There were no significant differences over time in DAS28–3, tender joints, inflammatory markers, according to HBsAg-positivity, while swollen joints showed significant difference over time. ALT level did not showed time-association and group differences. HBsAg-positive RA patients were less likely to receive methotrexate and more likely to receive sulfasalazine. Disclosure of Interest None declared

SAT0338 Clinical Characteristics and Treatment Outcomes of Patients with Chronic Periaortitis

Background Chronic periaortitis (CP) is rare disease that involves the aorta which is characterized by a fibro-inflammatory periaortic cuff in imaging studies and adventitia-predominant inflammation and fibrosis in histopathology. Associations between aortitis and idiopathic retroperitoneal fibrosis, inflammatory abdominal aortic aneurysm had been reported, and this spectrum of disorders is now categorized as CP. CP has aroused controversy on the question of incorporating it into the spectrum of primary large vessel vasculitis. Recent investigations have documented significant overlap between CP and the newly recognized systemic inflammatory disorder known as IgG4-related disease (IgG4-RD), suggesting that at least a fraction of cases of CP might be IgG4-RD. Objectives The aim of this study is to investigate clinical characteristics and treatment outcomes of patients with CP. Methods A retrospective review was performed on 2,496 patients who visited Samsung Medical Center between January 2004 and December 2014. Patients compatible with CP based on characteristic imaging findings of fibrosclerosing encasing lesions around the aorta were enrolled. The clinical, radiological, histopathological features, treatments and outcomes of patients were analyzed. Additionally, patients were further classified into two subgroups: IgG4-related and non IgG4-related CP according to the comprehensive diagnostic criteria for IgG4-RD proposed by a Japanese study, and comparison of the subgroups was performed. Patients without an initial serum IgG4 level or with a history of prior treatment were excluded from this analysis. Results A total of 61 patients with CP were identified. Patients showed a male predominance with the median age of 61 at diagnosis. The abdominal aorta was the most commonly involved site (84%), and half of the patients had aortic lesion confined to the abdominal aorta without involvement of the thoracic aorta. The thoracic aorta was involved in 46% of patients. Only 2 (3%) patients had stenotic lesions of the aorta, while 19 (31%) patients had aneurysmal changes of the aorta. Ureteral obstruction was found in 30% of patients. 49 (80%) patients received glucocorticoids with a median initial dose of 50 mg per day as prednisolone. 19 (31%) patients received additional immunosuppressant including azathioprine, methotrexate and mycophenolate. Nine patients underwent vascular surgery including seven cases of surgical abdominal aorta aneurysm repair, two cases of aortic valve replacements and four patients underwent endovascular abdominal aneurysm repair during their disease course. Overall 60% of patients achieved remission without relapse during the course. When the Japanese criteria for IgG4-RD were applied to patients, ten were classified as IgG4-related and twenty-five as non IgG4-related. The overall male predominance did not differ and there were no significant differences in clinical features, treatments and outcomes between two groups, with the exception of older age (median 69 vs. 59 years, p=0.021), higher serum globulin, IgG and IgG4 levels and greater pancreas involvement in IgG4-related patients (30% vs. 0%, p=0.018). Conclusions We identified 61 patients with CP. Further integrated investigations into pathogenesis, practical diagnostic criteria and markers for disease activity and prognosis are warranted. Disclosure of Interest None declared

AB0793 Clinical Characteristics of Hip Arthritis in Patients with Ankylosing Spondylitis in Korea

Objectives This study aimed to evaluate the clinical characteristics and associated factors of hip arthritis in patients with ankylosing spondylitis (AS). Methods A retrospective analysis evaluated 488 patients of AS with hip arthritis at a single tertiary hospital in South Korea. Hip arthritis was assessed by Bath Ankylosing Spondylitis Radiology Hip Index (BASRI-h) and the average joint space width of the hip joint at three distinct sites that are in between the acetabulum and femoral head at baseline and last visit of outpatient clinic. Clinical and laboratory characteristics were collected. Results Among 488 patients with AS, 60 (12.3%) patients had hip arthritis. Body mass index (BMI) and erythrocyte sedimentation rate (ESR) were associated with hip involvement in AS (OR 1.11, 95% CI 1.03 to 1.19, p=0.008 and OR 1.01, 95% CI 1.00 to 1.02, p=0.005, respectively). The mean X-ray follow-up duration was 81.4±35.7 months. During the follow-up period, ESR and C-reactive protein (CRP) decreased significantly and there was no significant radiographic change in the hip joints. Among 60 patients, 7 (11.7%) patients had radiographic progression of the hip joints and 5 (8.3%) patients had hip replacement surgery. The BMI tended to be higher in patients with radiographic progression of the hip joints than in those without (23.4±4.2 vs. 26.6±3.9, p=0.068). Conclusions Most of the patients with hip arthritis in AS had no significant radiographic progression during the follow-up period. BMI was associated with hip involvement in patients with AS. Disclosure of Interest None declared

FRI0352 Decline of Lung Function is Associated with the Presence of Rheumatoid Factor in Korean Subjects Without Clinically Apparent Lung Diseases

Background Rheumatoid factor (RF) is an autoantibody directed against the Fc component of IgG. It is present in approximately 70-80% of rheumatoid arthritis (RA) patients but also found nonspecifically in chronic inflammatory condition such as sarcoidosis, hepatitis B or C, and tuberculosis. Meanwhile, in relation to RA-related autoantibodies, airways abnormalities were reported in patients without inflammatory arthritis and the lung has been suggested as a potential site of generation of RA-related autoimmunity. In subjects without any specific medical problem, however, the influence of RF to lung function is infrequently known. Objectives This study aimed to determine the effect of the presence of RF on pulmonary function in a large number of Korean healthy subjects without any history of joint disease and clinically apparent lung diseases. Methods Of the 114,944 people who participated in a health checkup program in 2010, 94,438 subjects with normal chest radiography were recruited, whose results of RF and pulmonary function test (PFT) using spirometry were available. Subjects with arthralgia or the past medical history of arthritis including RA, and lung diseases were excluded based on self-reported questionnaire. Association between RF and PFT was assessed by correlation analysis. Results Among 94,438 people, RF was positive in 3,326 subjects (3.52%). Their mean age was 41.3±8.3 (range, 21 – 83) and 43.8% were female; these characteristics were not significantly different from those of RF-negative subjects, whose mean age was 41.3±8.3 (range, 18 – 88) and 43.7% female. Ever-smokers (ex- and current smokers) were 39% in RF-positive subjects while 41.2% in RF-negative subjects (p=0.009). Hepatitis B surface antigen (HBsAg) and anti-hepatitis C antibodies (anti-HCV) were more frequently seen in RF-positive subjects (12.1% vs. 3.5%, p<0.001 for HBsAg and 0.5% vs. 0.1%, p<0.001 for anti-HCV). Regarding PFT, RF-positive subjects had lower forced vital capacity (FVC) and forced expiratory volume in one second (FEV1) compared to RF-negative subjects (3.79±0.83 L vs. 3.87±0.83 L, p<0.001 and 3.17±0.66 vs. 3.25±0.67 L, p<0.001). The proportion of subjects with FVC below 82% and FEV1 below 84% of the predicted value was significantly higher in RF-positive subjects (50.7% vs. 46.6%, p<0.001 and 54.5% vs.49.4%, p<0.001) but the frequency of airflow limitation (FEV1/FVC ≤70%) did not differ between two groups (1.4% vs. 1.5%, p=0.47). FVC and FEV1 had negative correlations with the RF titers and the strength was very weak (r = -0.053, p<0.001 in FVC and r = -0.055, p<0.001 in FEV1). Conclusions The results suggest that RF could impact on lung function in healthy subjects without clinically apparent lung diseases. A follow up study for the serial changes of PFT may reflect the actual influence of the raised RF titers. Disclosure of Interest None declared