Background Biologic disease modifying anti-rheumatic drugs (DMARDs) have also become an important arsenal in treating inflammatory arthritides in Korea; nearly ten agents are currently used nationwide in daily clinical practice. Despite numerous studies describing adverse events or treatment strategies of biologics have been published in the literature, long-term data or guidelines tailored for Korean patients are absent at this point. Objectives To establish a multi-arm nationwide Korean biologics registry for patients with systemic rheumatic disease Methods The committee for Korean Biologics Registry for patients with systemic rheumatic disease (KOBIO) was launched supported by the Korean College of Rheumatology (KCR) in 2012. Rheumatoid arthritis (RA), ankylosing spondylitis (AS), psoriatic arthritis (PsA) were the target systemic rheumatic diseases. The primary endpoint of the registry was to assess the adverse events (terminology defined by Meddra) associated with biologic use in Korea nationwide. Clinical data was first obtained via paper forms in each clinic, followed by data upload to the web-based electronic form (, NCT01965132). Patients to start or switch to any biologic were eligible for registration. KOBIO-RA patients was paired with age- and gender- matched patients prescribed with non-biologic DMARDs. Considering the primary goal of KOBIO, follow up data was obtained upon switching or discontinuation of the registered primary biologic agent. Results The ten arms of KOBIO (RA, AS, PsA) consisted of 1. Patient demographic data, 2. Comorbidities, 3. Disease activity, 4. Biologic agent, 5. Risk factor for adverse events, 6. Medications, 7. Imaging, 8. Extraarticular function, 9. Patient function, and 10. Laboratory findings (Figure). Thirty eight institutes nationwide enlisted to the KOBIO network. In the first year, total 1064 patients were registered (2013.1.1- 2013.12.31). The baseline demographic data of the patients are depicted below (Table). A unique feature of this registry is that the submenu of each arm is accustomed to respective disease entities; thus the data of KOBIO-RA, AS, and PsA can be filed and even compared between one another efficiently. On every patient follow up, biologics-related, or non-related adverse events was recorded in arm 5, under a new title 5. Outcome. Conclusions KOBIO is a recently established web-based nationwide biologics registry focusing on the prevalence and characteristics of adverse events in Korean RA, AS, and PsA patients using biologics. Ongoing data acquisition will be analyzed to elucidate any dissimilarities in adverse events between Korean patients and other ethnic groups. Acknowledgements The KOBIO registry is supported by the Korean College of Rheumatology. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.3505

Background Although subclinical liver disease is common in SLE, strikingly high levels of liver enzymes are rare. Liver enzyme abnormalities in lupus are multifactorial and can be drug induced or caused by disease activity. Objectives Our aim was to determine the cause of high levels of liver enzymes in lupus patients, particularly in patients diagnosed with toxic hepatitis. Methods We performed a retrospective chart review of SLE patients treated at the Inje University Hospital between 2001 and 2013. We defined liver enzyme abnormality as a ≥2 fold increase in 2 or more of the 4 components: bilirubin, AST, ALT and LDH or ALP. Toxic hepatitis was diagnosed by a score 5 in the Roussel Uclaf Causality Assessment Method (RUCAM) and classified according to their pattern of liver enzyme: cholestatic, hepatocellular and mixed. Results Clinical and laboratory findings of liver disease was reviewed in 301 SLE patients who met ≥4 ACR criteria. Of 301 SLE patients, 74 (24.6%) met strict criteria for the liver enzyme abnormality and had the following diagnoses: toxic hepatitis (n=20), viral hepatitis (n=3), autoimmune hepatitis (n=5), liver enzyme elevation associated with infection (n=4) and an indeterminate clinical diagnosis, presumably associated with lupus activity (n=42). In total, 20 patients (6.6%) had presumed toxic hepatitis associated with either herbal medicines (n=8), anti-tuberculosis (Tb) drug (n=4), antibiotics (n=5), NSAIDS (n=1), or anticonvulsant drug (n=2). There were striking abnormalities in patients with toxic hepatitis (mean peak values: AST 610±551 U/L, ALT 369±352 U/L, ALP 598±387 U/L, LDH1,128±761 U/L). 5 had a cholestatic pattern, 9 had a hepatocellular pattern, 3 had a mixed pattern and 3 were undeterminated. Among the 20 patients with toxic hepatitis, 17 were found to have active lupus (SLEDAI≥4). After cessation of the suspected causative medication and subsequent steroids treatment, liver enzymes were improved. Number Age Cause RUCAM SLEDAI bilirubin AST ALT ALP LDH 1 47 Herb 6 3 0.5 87 352 2 23 Herb 6 10 4.9 659 130 995 1407 3 25 Herb 5 16 0.8 625 135 1268 1049 4 71 Herb 7 17 1.6 695 195 1046 1227 5 30 Herb 5 10 0.3 79 100 144 563 6 32 Herb 6 24 1.9 1144 275 699 1681 7 41 Herb 6 14 0.7 764 1545 922 1832 8 21 Herb 7 8 0.4 114 217 268 204 9 28 Ceftriaxone 6 4 0.5 186 228 177 10 39 Ceftazidime 6 18 0.2 123 182 182 11 27 Pip/TZ 5 4 0.2 66 52 599 637 12 20 Ceftazidime 5 10 0.8 1267 369 1001 3422 13 26 Pip/TZ 8 16 243 413 518 14 20 Anti-Tb 5 3 1.2 260 105 178 1249 15 23 Anti-Tb 8 2 11 1729 915 438 16 48 Anti-Tb 7 25 0.4 590 201 1095 1190 17 22 Anti-Tb 9 4 0.3 1942 726 536 862 18 36 Phenytoin 5 14 0.5 584 542 505 380 19 21 Valproic acid 8 13 0.9 835 449 329 1547 C, cholestatic; H, hepatocellular; M, mixed Pip/Tz; Piperacillin/Tazobactam. Conclusions In our study, herbal medicines was the most common cause of toxic hepatitis in Korean lupus patients. Antibiotics and anti-Tb drugs also could lead to toxic hepatitis in lupus patients. Since...

Background Early and aggressive treatment offers better outcomes in early rheumatoid arthritis (RA). The long-term effect of early treatment and effect of early treatment on functional disability have not been studied. Objectives To determine whether early diagnosis and treatment have long-term benefits for disease activity and functional disability in patients with RA enrolled in the KORean Observational study Network for Arthritis (KORONA). Methods A total of 4540 rheumatoid arthritis patients completed questionnaires to establish their demographic profile, medical history, disease-specific outcomes, and RA-related information. We defined early and delayed RA diagnoses as lag-times of shorter than and at least 1 year. Disease activity was measured with the DAS28–ESR, and it was dichotomized using a score of 2.6. Functional disability was measured with the Korean HAQ-DI, and was dichotomized using a score of 1. We used the chi-square test and t-test to identify differences between male and female patients, and crude and multiadjusted models to identify the impacts of early diagnosis on disease activity and functional disability. Results In crude and multiadjusted models, early diagnosis was not associated with a higher remission rate (OR 1.10, CI 0.94-1.28 in crude model, OR 1.05, CI 0.83-1.32 in multiadjusted model). We performed subgroup analysis according to disease duration; there was no association between early diagnosis and remission rate. Early diagnosis was associated with functional disability in crude model (OR 0.79, CI 0.68-0.91) but not in multiadjusted model (OR 0.85, CI 0.72-1.002). In subgroup analysis according to disease duration and disease activity, early diagnosis was independently associated with functional disability for a shorter disease duration (OR 0.78, CI 0.63-0.96 in disease duration <10 years) and the presence of moderate-to-severe disease activity (OR 0.83, CI 0.69-0.99 in DAS28-ESR ≥3.2). Image/graph Conclusions Early diagnosis is associated with functional disability especially with a disease duration of less than 10 years and the presence of moderate-to-severe disease activity. Disclosure of Interest None Declared

Background The importance of tight control is supported by solid clinical evidence. While treating RA with the aim of achieving remission or a low disease activity-as determined by disease activity score employing 28 joints count (DAS28) or the simplified and the clinical disease activity index (SDAI, CDAI) -is reasonable and important, this approach is not widely accepted in the clinical situation. Objectives To identify the effects of tight control of rheumatoid arthritis (RA) on various disease outcomes in a large observational study. Methods We selected 1900 RA patients with a baseline DAS28-ESR of more than 3.2 and who had 1 year of follow-up data. The patients were divided into two groups: (1) disease-modifying antirheumatic drugs (DMARDs)-changed group (patients who changed the types or amounts of their DMARDs) and (2) DMARDs-unchanged group (patients who maintained their DMARDs). We measured various disease outcomes, including the Health Assessment Questionnaire–Disability Index (HAQ-DI), DAS28-ESR, C-reactive protein (CRP), ESR, and global health assessments by both physicians and patients. The t-test was used to identify the effects of tight control of RA on various disease outcomes. Results Patients in the DMARDs-changed group were younger, had a shorter disease duration, used less leflunomide, used more biologic agents. At baseline, they had higher DAS28-ESR (4.62±0.96 in DMARDs-changed group versus 4.42±0.90 in DMARDs-unchanged group, p<0.001), CRP (1.15±1.62 versus 0.81±1.14, p<0.001), global health assessment by both physician (34.05±20.00 versus 26.94±18.16, p<0.001) and patient (48.96±25.34 versus 46.18±24.74, p=0.016). In the comparison between baseline and the 1-year follow-up, the DMARDs-changed group showed greater improvements in HAQ-DI (–0.76±1.43 versus –0.59±1.22, p=0.006), CRP (–0.39±1.71 versus –0.11±1.37 mg/dl, p=0.001), and the global health assessment by a physician (–11.21±24.18 versus –8.10±19.20, p=0.002). Image/graph Conclusions Immediate changes in DMARDs according to disease activity can improve disease outcomes, especially DAS28-ESR, CRP, and the global health assessment by a physician. Disclosure of Interest None Declared

Background In genetically susceptible individuals, we suspect that other environmental factors, which are yet to be determined, induce epigenetic changes that result in the development of rheumatoid arthritis (RA). However, to our knowledge, a genome-wide profile of DNA methylation changes in RA is not yet available. Objectives To investigate the possible epigenomic biomarker of RA pathogenesis, the CpG methylation profiles of peripheral whole blood were analyzed using microarray profiling. using methylated DNA isolation assay (MeDIA)-CpG promoter microarray, and compared it with peripheral whole blood of healthy controls. Methods Human peripheral whole blood samples were obtained from 16 RA and from 16 age, sex-matched healthy vontrols. Total genomic DNA extracted using the QIAamp DNA mini and blood kit protocol (Qiagen, Hilden, Germany). To discover novel hypermethylated genes in RA by genome-wide search, we introduce a MeDIA-coupled CpG microarray method for directly identifying differentially methylated regions of the genomes in each pooled whole blood between RA patients and healthy controls. A minimized methyl-DNA binding domain (MBD) tagged by histidine (MBD2bt) of human MBD2b was used, which provides high binding sensitivity to methylated DNA. Four independent CpG microarray analyses with human 244K CpG island microarrays (Agilent, Santa Clara, CA) were done for screening of candidate gene. Results In four CpG microarray, 16 genes were screened as 2 fold hypermethylated targets among 267 porbes. Through stepwise subtraction processes, we finally selected four candidate targets. Among of these targets, four genes, LBX2, HOXA5, HUS1B, INPP5A gene in the promoter region have shown so far a significant increase in the methylation frequency in RA when compared with healthy controls (see figure 1). The methylation status of promising candidates will be validated by quantitative pyrosequencing assay in each samples. Figure 1. Candidate genes selection-screening. Conclusions LBX2, HOXA5, HUS1B, INPP5A gene in peripheral blood of RA patients can possibliy be a epigenomic biomarker. Pathophysiologic correlation and their role as a diagnostic or prognostic marker should be investigated by quantitative pyrosequencing in a larger number of patients group hereafter. References Costenbader KH, Gay S, Riquelme ME, Iaccarino L, Doria A. Genes, epigenetic regulation and environmental factors: Which is the most relevant in developing autoimmune diseases? Autoimmun Rev 2011: epub Ballestar E. Epigenetic alterations in autoimmune rheumatic diseases. Nat Rev Rheumatol 2011:7:263-71. van Baarsen LG, Bos CL, van der Pouw Kraan TC, Verweij CL. Transcription profiling of rheumatic diseases. Arthritis Res Ther 2009;11:207. Disclosure of Interest S.-H. Park Grant/Research support from: This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (2011-0007659)., S.-K. Kim: None Declared, J.-Y. Choe: None De...