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Background:Gout shows a seasonal variation that widely differs among geographic areas, and we previously reported a seasonal effect on gout in Korea. However, we had no information regarding changes in diet and had only limited laboratory data because this was a retrospective study in patients receiving a urate-lowering therapy. Therefore, we designed this prospective study to elucidate the seasonality and associated factors of gout attacks in Korea.Objectives:To evaluate the seasonality and associated factors of the incidence of gout attacks in Korea.Methods:We prospectively enrolled patients with gout attacks who were treated at nine rheumatology clinics between January 2015 and July 2018 and followed them for 1-year. Demographic data, clinical and laboratory features, and meteorological data including seasonality were collected.Results:Two hundred-five patients (males, 94.1%) were enrolled. The proportion of patients with initial gout attacks was 46.8% (n = 96). The mean age, body mass index, attack duration, and serum uric acid level at enrollment were 50.5 years, 26.1, 10.2 days, and 7.3 mg/dL, respectively. Gout attacks were most common during spring (43.4%,P< 0.001) and in March (23.4 %,P< 0.001). A similar pattern of seasonality was observed in the group with initial gout attacks. Alcohol was the most common provoking factor (39.0%), particularly during summer (50.0%). The mean diurnal temperature change on the day of the attack was highest in the spring (10.3°C), followed by winter (9.1°C), summer (8.1°C), and fall (8.0°C) (P= 0.027). The mean change in humidity between the 2 consecutive days (the day before and the day of the attack) was significantly different among the seasons (3.4%, spring; 0.2%, summer; 0.4%, fall; -3.9%, winter;P= 0.015). One hundred twenty-five (61%) patients completed 1-year follow-up (51% in the initial attack group). During the follow-up period, 51 gout flares developed (18 in the initial attack group). No significant seasonal variation in the follow-up flares was found.Conclusion:In this prospective study, the most common season and month of gout attacks in Korea were spring and March, respectively. Alcohol was the most common provoking factor, particularly during summer. Diurnal temperature changes on the day of the attack and humidity changes from the day before the attack to the day of the attack were associated with gout attack in our cohort.References:[1]Choi HJ, Lee CH, Lee JH et al. Seasonality of gout in Korea: a multicenter study. J Korean Med Sci 2015;30:240-4.Disclosure of Interests: :None declared

Background Ankylosing spondylitis (AS) is a chronic inflammatory disease, which destructs spine. After ivnolvement of sacroiliac joint, inflammation usually spreads from lower L spine to C spine. But it is hard to evaluate radiographic changes in T spine due to air in lung by X-ray. Objectives We performed this study to find out how many patients have radiographic changes in T spine at first visit and if bone spurs of vertebral bodies are associated with radiographic changes in facet joints in spine. Methods We enrolled the patients who were diagnosed as AS by modified NY criteria in Kyung Hee university hospital at Gangdong in Seoul, South Korea from Mar 2008 to Dec 2015. After diagnosis, we performed a whole spine CT in each patient according to the routine protocol of our clinic to evaluate the radiographic involvement of spine. Total 1,170 patients were enrolled and analyzed. We examined the presence of bone spurs in vertebral bodies (VB) and radiographic changes of facet joints in L and T spine and costovertebral joints (CVJ). Results Of the 1,170 enrolled patients. 920 were men (79%) and 85% were HLA B27 positive. Incidences of past history of peripheral arthritis and uveitis were 29.0% and 30.6%, respectively. Mean age was 33.0 ± 10.0 years and mean disease duration was 10.5 ± 9.5 years. 34.1% of patients had at least one bone spur and 26.3% had at least one lesion in facet joints in L spine. In T spine, 47. 2% of patients had already at least one bone spur, 28.2% had at least one lesion in facet joints. 32.8% had already at least one lesion in CVJs. Each radiographic change is associated with one another (p=0.00). These all radiographic changes were significantly more frequently observed in the patients with old age and long disease duration at the point of diagnosis (p=0.00). The lesion of CVJs and facet joints in T spine were observed more frequently in male than female significantly (respectively p=0.02, 0.00). 19.2% of the patients had radiographic changes in T spine without in L spine. Conclusions At the point of diagnosis, many patients already had radiographic changes in T spine. We suggest if radiographic change of T spine is included in radiographic progression score system such as mSASSS, we can more sensitively detect radiographic progression even in a short interval. Disclosure of Interest None declared

Background Ankylosing spondylitis (AS) is a chronic inflammatory arthropathy, which primarily affects the sacroiliac joints and axial skeleton. In AS, involvement of the facet joints results in both back pain, and limitation of spinal mobility. Involvement of facet joint in AS have been reported in several articles. Improvements in spinal mobility in AS after treatment with tumor necrosis factor (TNF) inhibitors have been reported. However, TNF inhibitors were reported to increase or to not inhibit structural damage progression in AS, as assessed using plain radiography. It seems logical that improvement in spinal mobility by TNF inhibitors would result from their effects on facet joint. Objectives To study the effect of TNF inhibitors on progressive facet joint damage in AS patients. Methods AS patients who were treated with TNF inhibitors and had 2 sets of spinal computed tomography (CT) scans, a median of 50.96±5.47 months apart, were included (n=25). Radiographic severity of facet joints was assessed by a new scoring system using CT. Total facet joints from C2-C3 to L5-S1 were scored: erosions 1, subchondral sclerosis 2, partial ankyloses 3, and total ankyloses 4. We compared the longitudinal effects of TNF inhibitors with non-TNF inhibitor treatment by scoring of facet joint of 25 AS patients who were not treated by TNF inhibitors. Results The mean age were 30.9±6.7 years and no significant differences in gender distribution (male, 84% vs. 88%). The only significant difference between two groups was that TNF inhibitor treated group had longer disease duration (years, 4.15±4.02 vs. 2.13±1.73, p=0.001). Significant increases in CT score in the total spine and T-spine were observed in both groups at follow-up time points (Table 1). The rates of increase in CT score of the total spine were similar in both groups, whereas, the rates of increase in CT score of the T-spine was lower in the TNF inhibitor treated group than in the non-TNF group. However, the difference was not statistically significant (p=0.387; Fig. 1). Conclusions Treatment with TNF inhibitors did not prevent the radiographic progression of facet joints damage in AS patients References Wilkinson M, Bywaters EG. Clinical features and course of ankylosing spondylitis; as seen in a follow-up of 222 hospital referred cases. Ann Rheum Dis. 1958;17:209-28. 2Machado MA, Barbosa MM, Almeida AM et al. Treatment of ankylosing spondylitis with TNF blockers: a meta-analysis. Rheumatol Int. 2013;33:2199-213. Disclosure of Interest None declared

Background Long-term treatment of anti-TNF agents in patients with immune mediated disease can increase the risk of active tuberculosis infection (ATBI) by reactivation of latent tuberculosis infection (LTBI) or de novo infection. CT-P13 is a biosimilar of innovator infliximab (INX), approved by the EMA in 2013 based on the studies PLANETAS and PLANETRA. Objectives To identify the risk of positive conversion in the QuantiFERON®-TB Gold in-tube (QTF) test over 2 years in ankylosing spondylitis (AS) and rheumatoid arthritis (RA) patients receiving CT-P13 or INX in the extension studies of PLANETAS and PLANETRA, in 17 countries with various TB incidences. Methods Of 476 enrolled subjects in extension studies of PLANETAS or PLANETRA, all patients had QTF test at baseline and at least one follow-up QTF result after study drug exposure for a 110-week period. Patients with positive QTF result at baseline received prophylaxis before study drug exposure. Patients received either CT-P13 or INX (5mg/kg in AS; 3mg/kg in RA) by usual schedule up to week 102. Countries were divided into four risk groups according to TB incidence, as listed in the 2013 WHO TB report: very low (0–19/100000 population), low (20–49), intermediate (50–124) and high (≥125). In prevalent countries, QTF was performed at weeks 14, 30, 54, 62 and 110. In countries with low risk, QTF was performed at weeks 62 and 110 (or the end of the study visit). To identify the positive conversion in QTF test, patients with negative result at baseline were included in this analysis. Results Among 458 patients with negative QTF at baseline, median dose is 15 (range 9 to 15) and all patients had at least one QTF result after 9th dose exposure. Positive conversion of QTF was observed in 16.6% (76/458) of patients (AS 18.5% [31/168]; RA 15.5% [45/290]). The results showed a tendency of higher positive conversion rate in the region where the TB incidence is high (very low 9.3%, low 11.4%, intermediate 21.7%, high 52.0%). Relative risk (RR) of positive conversion in intermediate and high vs. very low and low TB incidence countries was 2.37 (95% CI 1.57 to 3.59). Non-white ethnicity had higher RR of positive conversion in very low and low TB incidence countries (RR 3.83, 95% CI 2.04 to 7.21), and intermediate and high TB incidence countries (RR 3.11, 95% CI 1.89 to 5.10) as well. In very low, low, intermediate and high incidence countries, positive conversion was observed in 9.3%, 8.5%, 19.6% and 48.0% of patients at week 62, and 0%, 3.0%, 2.1% and 4.0% of patients after week 62 over 2 years, respectively. Amongst patients who had positive conversion, 76.3% (58/76) of patients received prophylactic TB medication. Conclusions To reduce TB incidence in patients receiving anti-TNF agents, appropriate screening and serial QTF tests at least during the first two years of treatment are necessary to reduce and minimize the risk of TB in patients residing in intermediate and high TB endemic regions. Disclosure of Interest W. Park Grant/research support: CELLTRION, Inc., Consultant for: CELLTRION, Inc., Speakers bureau: CELLTRION, Inc., D. Yoo Grant/research support: CELLTRION, Inc., Consultant for: CELLTRION, Inc., Speakers bureau: CELLTRION, Inc., P. Hrycaj Grant/research support: CELLTRION, Inc., N. Prodanovic Grant/research support: CELLTRION, Inc., P. Miranda Grant/research support: CELLTRION, Inc., E. Ramiterre Grant/research support: CELLTRION, Inc., A. Baranauskaite Grant/research support: CELLTRION, Inc., P. Wiland Grant/research support: CELLTRION, Inc., Y.-A. Lee Grant/research support: CELLTRION, Inc., S. Lee Employee of: CELLTRION, Inc. DOI 10.1136/annrheumdis-2014-eular.3492

Background Endocan, previously called endothelial cell-specific molecule (ESM-1), has been studied as a pro-angiogenic factor in tumor tissues. Endocan binds CD11a/CD18 integrin (also called LFA-1 for Leukocyte Function-associated Antigen-1) on human leukocytes, consequently inhibiting its binding to ICAM-1 and preventing transendothelial migration. These physiological functions of endocan may also be involved in the angiogenesis of pannus in rheumatoid arthritic joints, which shows tumor-like growth. Here, we describe for the first time that endocan expression is increased in arthritic synovial tissues and that adiponectin is one of the important factors that increases endocan expression in synovial cells. Objectives This study was performed to evaluate whether endocan expression, which is known to be involved in tumor angiogenesis, is increased in rheumatoid arthritic tissues. In addition, we examined the contribution of adiponectin in the regulation of endocan expression in arthritic joints. Methods Arthritic synovial tissues from patients with rheumatoid arthritis (RA) and osteoarthritis (OA) were immunostained with antibodies to endocan and VEGF. Synovial cells and human umbilical vein endothelial cells (HUVEC) were cultured and stimulated with IL-1β and/or adiponectin. The mRNA and protein levels of endocan were measured by PCR and ELISA, respectively. Results Endocan expression was greatly increased in inflammatory sites of RA synovial tissues. In OA tissues, its expression was higher in tissues with moderate to severe inflammation than in those with mild inflammation. In vitro expression levels of endocan and VEGF in endothelial and synovial cells were differentially increased in response to IL-1β stimulation. Adiponectin was a more potent stimulator of endocan than was IL-1β at their respective physiological concentrations in synovial cells. Endocan silencing by siRNA transfection in synovial cells decreased in vitro cell migration and invasion. Conclusions Adiponectin is an important factor in the stimulation of endocan expression in synovial cells. Adiponectin-induced endocan expression in synovial cells may stimulate cell migration and invasion as well as angiogenesis in the pannus of arthritic joints. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.3705

Background It has been shown that patients with rheumatoid arthritis (RA) experience cardiovascular (CV) events more often than expected. Increased risk of CV disease in RA patients cannot be fully explained by conventional CV risk factors. This raises the possibility that the systemic inflammatory burden in RA may bring about its high CV event rate by causing accelerated atherosclerosis Objectives This study was designed to evaluate the extent of subclinical atherosclerosis by measuring intima-media thickness of the carotid arteries (C-IMT) and the presence of plaque among RA patients and controls and to determine whether subclinical atherosclerosis such as increased C-IMT or plaque presence, RA associated features, and other conventional CV risk factors are associated with later development of CV disease in RA patients Methods C-IMT was measured in 126 RA patients and 85 OA patients as controls who had no experience of CV events. The C-IMT was evaluated at common carotid arteries (CCAs), carotid bifurcation (BF) and internal carotid arteries (ICAs), bilaterally. Mean and maximal (max) IMTs were calculated from three measurements at each site. The following data were obtained for every patient: age, sex, body mass index (BMI), presence of bone erosions, rheumatoid factor, anti-CCP, medications, hypertension, hypercholesterolemia, diabetes mellitus, smoking status, family history of CV diseases, ESR and CRP levels. Thereafter, these patients have been followed-up and examined the CV event rate during seven years. The CVD was defined as myocardial infarction, unstable angina, cardiac arrest, or death due to ischemic heart disease. Results Unlike expectations, mean and max C-IMT did not show the difference between RA and OA patients. But, we found the higher presence of carotid plaque in RA patients than in OA patients. During follow-up, 21patients experienced CV events. The incidence of CV events was higher in RA than OA (15.0% vs. 3.5%,p=0.004). But, the conventional CV risk factors such as DM, hypertension and high BMI were fewer in RA than in OA (10.3%,27.7%,34.1% vs. 28.2%,55.2%,57.6%,p=0.000). More CV events occurred in RA patients who initially showed the presence of subclinical plaque and the duration of CV event-free survival was shorter in RA patients with carotid plaque than those without (10 vs. 31months,p=0.051). The RA patients who developed CVD later had more bony erosion, higher positivity for rheumatoid factor or anti-CCP, high dose of steroid and higher levels of ESR and CRP, than those who did not. Conclusions Despite a favorable conventional CV risk profile, our RA patients had significantly increased incidence rate of CVD than OA patients. RA itself was an independent risk factor for CVD. Especially, RA patients with carotid plaque, seropositivity, bony erosion, higher ESR and CRP, and high dose of used glucocorticoids are at higher risk of CVD. Disclosure of Interest None Declared

Background The role of adiponectin in the pathogenesis of rheumatoid arthritis was previously studied in relation to the production of IL-6, IL-8, vascular endothelial growth factor (VEGF), and matrix metalloproteinases (MMPs) in fibroblast-like synoviocytes (FLS). Objectives This study was performed to evaluate the contribution of adiponectin to the production of IL-6, IL-8, VEGF, MMP-1, and MMP-13 in human endothelial cells and osteoblasts in arthritic joints. Methods Cultured human umbilical vascular endothelial cells (HUVEC) and osteoblasts were stimulated with adiponectin (1 or 10 μg/ml) or IL-1β (0.1 ng/ml) in the presence or absence of hypoxia for 24 hrs. The gene expression patterns of culture supernatants and cells were analyzed by ELISA and PCR, respectively. Results Adiponectin significantly stimulated the expression of VEGF, MMP-1, and MMP-13 in osteoblasts but not in HUVEC, while it significantly stimulated the expression of IL-6 and IL-8 in both HUVEC and osteoblasts. The increase of VEGF expression by adiponectin was significantly higher than that by IL-1β stimulation. The expression of IL-6 and IL-8 in adiponectin-stimulated HUVEC was about 10-fold higher than that of IL-1β, but about 2-fold higher in osteoblasts. In addition, IL-8 expression levels in HUVEC were about 7-fold higher than that of osteoblasts. However, IL-6 levels were similar between the two cell types, suggesting that adiponectin may be involved in the production of IL-8 in endothelial cells, which may play an important role in neutrophil recruitment to arthritic joints. Furthermore, the increases observed in gene expression by adiponectin were differentially regulated by hypoxia. Conclusions Adiponectin plays a more important role in the production of mediators driving synovitis and joint destruction in endothelial cells and osteoblasts than that of IL-1β at physiological concentrations. References Arthritis Res Ther 2009, 11 (6):R161 Acknowledgements Basic Science Research Program through the National Research Foundation of Korea (NRF) (grant numbers 2010-0024089 and 2011-0009061) Disclosure of Interest None Declared

Background Even though it is well known that adipokines play important roles in the pathogenesis of RA, the in vivo role of adipokines and their association with disease activity is poorly understood. In particular, the modulation of serum adipokines (adiponectin, leptin, resistin, and visfatin) by RA disease activity or type of therapy including disease-modifying antirheumatic drugs (DMARDs) and tumor necrosis factor (TNF)-α blockers should be more elucidated. Objectives This study aimed to determine if disease activity and type of therapy in patients with rheumatoid arthritis (RA) differentially modulates serum adipokine levels and if pre-therapy adipokine levels contribute to treatment resistance. Methods Fasting blood samples from 40 patients with RA were collected at baseline and six months after therapeutic treatment with disease-modifying antirheumatic drugs (DMARDs) and/or tumor necrosis factor (TNF)-α blockers. Serum levels of adiponectin, leptin, visfatin, and resistin were measured by ELISA. Results Baseline adipokine levels were not significantly different between patients with moderate and high disease activity based on Disease Activity Score (DAS) 28. Among adipokines, only adiponectin was significantly increased in patients who responded to DMARD and/or TNF-α blocker therapy based on ACR20 at six months (from 2,964±1,237 to 3,683±1,511, P Conclusions Adipokine levels (adiponectin, leptin, visfatin, and resistin) are differentially modulated by disease activity and type of therapeutic treatment in patients with RA. Adipokine level may not contribute to therapeutic resistance to DMARD and/or TNF-α blocking agents. References Trayhurn P, Wood IS: Adipokines: inflammation and the pleiotropic role of white adipose tissue. Br J Nutr 2004, 92(3):347-355. Cansu B, Cansu DU, Kasifoglu T, Gulbas Z, Korkmaz C: Disease-modifying antirheumatic drugs increase serum adiponectin levels in patients with rheumatoid arthritis. J Clin Rheumatol 2011, 17(1):14-17. Disclosure of Interest None Declared

Background CT-P13 was developed as a biosimilar product to infliximab (Remicade®), a chimeric monoclonal antibody approved in the European Union in 1999 for the treatment of rheumatoid arthritis (RA), ankylosing spondylitis (AS), Crohn’s disease, ulcerative colitis, psoriasis, and psoriatic arthritis. Objectives To compare the pharmacokinetic (PK) profile of CT-P13 with that of infliximab at steady state in terms of area under the concentration-time curve over a dosing interval (AUC τ ) and observed maximum serum concentration (C max,ss ), and evaluate the efficacy and overall safety of both treatments in patients with AS. Methods Two hundred fifty patients with active AS were randomized 1:1 to receive either CT-P13 or infliximab (5 mg/kg, 2-hour IV infusion per dose) at weeks 0, 2, and 6 (dose-loading phase) and at weeks 14, 22, and 30 (maintenance phase). Ratios of geometric means of primary PK parameters (AUC τ and C max,ss ) from the 2 treatment arms between weeks 22 and 30 were subjected to ANCOVA analysis at 90% confidence intervals (CIs). Efficacy measures (including ASAS20 and ASAS40), and safety parameters (including the incidence of adverse events [AEs]) were also evaluated. This report presents PK, efficacy, and safety results up to week 30 (as approved by the European Medicines Agency). Results The mean (% CV) AUC τ was 34855.45 (34.3%) μg-h/mL and 34688.71 (45.4%) μg-h/mL in the CT-P13 and infliximab arms, respectively. The mean (% CV) C max,ss was 153.52 (27.6%) μg/mL and 150.39 (26.9%) μg/mL in the CT-P13 and infliximab arms, respectively. The ratio (%) between the geometric means of the AUC τ and C max,ss values in the CT-P13 and infliximab arms were 104.1% (90% CI 93.9% to 115.4%) and 101.5% (90% CI 94.6% to 108.9%), respectively, between weeks 22 and 30, indicating PK equivalence in terms of AUC τ and C max,ss . Secondary parameters at week 30 were also comparable, including ASAS20 and ASAS40 response rates (70.5% for CT-P13 vs 72.4% for infliximab and 51.8% vs 47.4%, respectively). AEs considered by the investigators to be related to study treatment were reported in 57 (44.5%) patients and 58 (47.5%) patients in the CT-P13 and infliximab arms, respectively. Related AEs due to infection were reported for 24/128 (18.8%) patients and 22/122 (18.0%) patients in the CT-P13 and infliximab treatment groups, respectively. AEs due to infusion reactions considered related to study drug were reported in 5 patients in the CT-P13 arm, and 6 patients in the infliximab arm. Tuberculosis was reported in 2 patients in the CT-P13 arm and in 1 patient in the infliximab arm. Conclusions CT-P13 and infliximab are equivalent in terms of AUC τ and C max,ss in patients with AS. In addition, CT-P13 was well tolerated, with an efficacy and safety profile comparable to that of infliximab up to week 30. Disclosure of Interest W. Park: None Declared, P. Hrycaj: None Declared, V. Kovalenko: None Declared, P. Miranda: None Declared, S. Gutierrez-Urena: None Declared, Y. Lee: None Declared, M. Lim: None Declared, C. Ahn: None Declared, H. Kim Employee of: Celltrion, D. Yoo: None Declared, J. Braun: None Declared

Background Chronic inflammation is known to be associated with increased cardiovascular (CV) event rate in rheumatoid arthritis (RA). Platelet activation may be a link in the pathophysiology of diseases leading to thrombosis and inflammation. Mean platelet volume (MPV), a platelet index, is an indicator of platelet activation. Several studies have shown increased MPV in RA patients compared to controls. But, the others reported that a RA patient may present a decreased MPV during active stages and later on will increase by different treatment regimens. Thus far, it is still not clear whether MPV increases or decreases with RA disease activities and over the duration of treatment. Objectives The current study was conducted to evaluate platelet function by measuring MPV in a selected population of newly diagnosed and untreated RA subjects. We also aimed to assess associations between MPV and seropositivity or other inflammatory markers. Finally we investigate the changes of MPV in response to disease-modifying anti-rheumatic drugs (DMARDs). Methods Newly diagnosed and DMARDs naive RA patients were recruited. We excluded those with established CV diseases or any conventional CV risk factors such as diabetes, hypertension, hyperlipidemia and smoking. Finally 92 RA patients (74 females, age: 49.8 ± 13.8 years) and 160 age- & sex- matched healthy subjects (120 females, age: 49.1 ± 11.6 years) as controls were enrolled for analysis. All patients started to receive DMARDs therapy including biologic agents (MTX: 70;76.1%, anti-TNF-alpha: 12;13.0%). They underwent thorough clinical and laboratory evaluation including MPV, platelet count, rheumatoid factor, anti-CCP, ESR, and CRP at baseline, 3 months, 6 months and 12 months. Seroposivity was defined to be positive for RF or anti-CCP. Results At baseline, MPV was lower in RA patients as compared to healthy controls (7.985 ± 0.916 vs. 7.988 ± 0.538 fL, p=0.002) and was negatively correlated with platelet counts and ESR levels (r:-0.244; p=0.022, r:-0.205; p=0.058, respectively). But, MPV was not correlated with the other inflammatory markers in patients with RA. Additionally, among RA patients, seropositive RA patients showed the significantly lower level of MPV than seronegative RA (7.973 ± 0.592 vs. 8.024 ± 1.580 fL, p=0.013). DMARDs therapy resulted in a significant increase in MPV only at 12 months after initiating treatment (7.985 ± 0.916, 8.015 ± 0.882, 7.926 ± 0.785, and 8.390 ± 0.766 fL at baseline, 3 months, 6 months and 12 months*, respectively; *p Conclusions The result of this study provides additional evidence supporting the previous reports that MPV is lower in active RA. We also found the correlation of MPV with seroposivity and long-term treatment response to DMARDs in RA patients. A decrease of platelet size as a result of increased turnover seems to be a mirror activity of RA. Disclosure of Interest None Declared