Choong Ki Lee

Effects of hypoxia/ischemia on catabolic mediators of cartilage in a human chondrocyte, SW1353.

Cells from a human chondrocyte cell line were studied in 1% oxygen and/or a lower glucose concentration (5.5 mM), compared to the routine culture conditions of normoxia and high glucose. HIF-1α, IL-1β, IL-6, IL-8, COX-2, TNFα, LIF, MMP-3, MMP-13, and reactive oxygen species (ROS) were evaluated, respectively. Effects of hypoxia inducing expression of HIF-1α were statistically significant at 72 h (p<0.05). Increased production of ROS by hypoxia was also observed with passage of time (p<0.05). The effects of hypoxia on HIF-1α and IL-1β were potentiated by 5.5 mM glucose, especially after 48 h (p<0.05). IL-8 production was significantly induced in 1% O(2), with 5.5 mM glucose (p<0.01). IL-8 mRNA expression and production in response to IL-1β were potentiated by hypoxia/ischemia (p<0.05, p<0.01, respectively). Up-regulation of IL-1β, ROS, and IL-8 by hypoxia/ischemia in human chondrocytes may occur in correlation with HIF-1α. IL-8 response to IL-1β may be potentiated synergically by hypoxia/ischemia, as an effector of hypoxia/ischemia. The results may suggest aggressive biology of the ordinary cartilage hypoxia/ischemia in the context of arthro-degeneration.

Effects of Methotrexate on Carotid Intima-media Thickness in Patients with Rheumatoid Arthritis

The purpose of this study was to evaluate the effects of rheumatoid arthritis (RA) and antirheumatic drugs on atherosclerosis by comparing carotid intima-media thickness (CIMT) as an indicator for cardiovascular diseases (CVD). This study included 44 female RA patients who met the 2010 ACR/EULAR criteria and age-matched 22 healthy females. CIMT was measured on both carotid arteries using a B-mode ultrasound scan. The mean value of both sides was taken as the CIMT of the subject. The CIMT was evaluated according to the use of drugs, disease activity and CVD risk factors in RA patients as a case-control study. Higher CIMT was observed in RA patients as compared with healthy subjects (0.705 ± 0.198 mm, 0.611 ± 0.093 mm, respectively, P < 0.05). With adjustment for the CVD risk factors, disease activity and the use of anti-rheumatic drugs, methotrexate (MTX) only showed a favorable effect on CIMT in RA. A significantly lower CIMT was observed in RA with MTX as compared with RA without MTX (0.644 ± 0.136 mm, 0.767 ± 0.233 mm, respectively, P < 0.05). The effects were correlated with MTX dosage (β = -0.029, P < 0.01). The use of MTX should be considered in high priority not only to control arthritis but also to reduce the RA-related CVD risk to mortality.

A case of acute pericarditis with hemophagocytic syndrome, cytomegalovirus infection and systemic lupus erythematosus

Hemophagocytic syndrome, cytomegalovirus infection and systemic lupus erythematosus (SLE) would each be critical diseases separately. Viral infections, autoimmune diseases or malignancies can complicate the Hemophagocytic syndrome. Cytomegalovirus infection is known to be prevalent in immune compromised hosts, and can exacerbate the symptoms of systemic lupus erythematosus. A 25-year-old man presented with fever and acute pericarditis with the hemophagocytic syndrome, cytomegalovirus infection and systemic lupus erythematosus; all developed concurrently at the onset of illness. With treatment, using ganciclovir and glucocorticoid medication the patient improved. Here we report this rare case and review the medical literature.

Factors Contributing to Discordance between the 2011 ACR/EULAR Criteria and Physician Clinical Judgment for the Identification of Remission in Patients with Rheumatoid Arthritis.

Remission is a primary end point of in clinical practice and trials of treatments for rheumatoid arthritis (RA). The 2011 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) remission criteria were developed to provide a consensus definition of remission. This study aimed to assess the concordance between the new remission criteria and the physician’s clinical judgment of remission and also to identify factors that affect the discordance between these two approaches. A total of 3,209 patients with RA were included from the KORean Observational Study Network for Arthritis (KORONA) database. The frequency of remission was evaluated based on each approach. The agreement between the results was estimated by Cohen’s kappa (κ). Patients with remission according to the 2011 ACR/EULAR criteria (i.e. the Boolean criteria) and/or physician judgment (n = 855) were divided into three groups: concordant remission, the Boolean criteria only, and physician judgment only. Multinomial logistic regression analysis was used to identify factors responsible for the assignment of patients with remission to one of the discordant groups rather than the concordant group. The remission rates using the Boolean criteria and physician judgment were 10.5% and 19.9%, respectively. The agreement between two approaches for remission was low (κ = 0.226) and the concordant remission rate was only 5.5% (n = 177). Pain affected classification in both discordant groups, whereas fatigue was associated with remission only by physician clinical judgment. The Boolean criteria were more stringent than clinical judgment. Patient subjective symptoms such as pain and fatigue were associated with discordance between the two approaches.

Factors associated with quality of life and functional disability among rheumatoid arthritis patients treated with disease-modifying anti-rheumatic drugs for at least 6 months

To determine characteristics of rheumatoid arthritis (RA) patients in Korea using disease‐modifying anti‐rheumatic drugs (DMARDs) for at least 6 months, and to identify factors associated with poor health‐related outcomes.

Age-related NADPH Oxidase (arNOX) Activity Correlated with Cartilage Degradation and Bony Changes in Age-related Osteoarthritis

The purpose of this study was to investigate the age-related NADPH oxidase (arNOX) activity in patients with age-related knee osteoarthritis (OA). Serum and cartilage arNOX activities were determined using an oxidized ferricytochrome C reduction assay. Full-thickness knee joint cartilages obtained through total knee replacement surgery were graded according to the Outerbridge (OB) classification. Radiographic severity of OA was determined on Knee X-rays according to the Kellgren-Lawrence (K/L) grading system. Cartilage β-galactosidase, HIF-1α, and GLUT-1 expression levels were evaluated as markers for tissue senescence, hypoxia, and glycolysis. Higher arNOX activities occurred with higher levels of cartilage β-galactosidase, HIF-1α, and GLUT-1 (P = 0.002). arNOX activity in cartilages with surface defects (OB grade II, III) was higher than in those without the defects (OB grade 0, I) (P = 0.012). Cartilage arNOX activity showed a positive correlation with serum arNOX activity (r = -0.577, P = 0.023). Serum arNOX activity was significantly higher in the OA subgroup with bilateral ROA than in the OA with no or unilateral ROA (2.449 ± 0.81, 2.022 ± 0.251 nM/mL, respectively, P = 0.019). The results of this study demonstrate that OA itself is not a cause to increase arNOX activities, however, arNOX hyperactivity is related to a high degree of cartilage degradation, and a high grade and extent of ROA in age-related OA. Graphical Abstract

THU0518 Characteristics, Outcomes, and Predictors of Complementary and Alternative Medicine use in Patients with Rheumatoid Arthritis

Background Use of complementary and alternative medicine (CAM) is not uncommon in patients with rheumatoid arthritis (RA), but patient characteristics and the factors influencing and predicting its use is not well known. Objectives We aimed to assess the characteristics and outcomes of CAM in patients with RA and to analyze the predicting factor for its use. Methods A total of 5,360 RA patients from the KORONA (Korean Observational Study Network for Arthritis) prospective multicenter cohort were assessed for use of CAM and characteristics including age, sex, disease duration, delay in diagnosis, family history, comorbidities, socioeconomic status, fatigue, sleep, pain, exercise, smoking, HAQ, EQ-5D, DAS28, medication, radiographic damage, surgery, and adverse events. Multiple logistic regression was used to analyze the predicting factors for CAM use. Results Of the 5,360 patients, 2,468 (46.0%) patients responded that they have used CAM. Acupuncture was most common (73.3%) followed by herbal medicine (60.4%), moxibustion (30.7%), bee venom (19.1%), others (7.7%), and placenta injection (3.9%). Female used CAM significantly more and CAM users were significantly younger at onset (p<0.01), had longer disease duration (p<0.01), more family history (p=0.02), lower income (p<0.01), and lower education status (p<0.01). CAM users reported significantly more fatigue (p<0.01), more sleep disturbance (p<0.01), more pain (p<0.01), worse general condition (p<0.01), higher HAQ score (p<0.01), and lower EQ-5D score (p<0.01). They also had significantly higher disease activity (p<0.01, more use of steroids (p<0.01) and NSAIDs (p<0.01), had more radiographic damage (p<0.01), underwent more surgery (p<0.01), and had more adverse events (p<0.01). One or more problem in any of the dimensions of EQ-5D was significantly associated with the use of CAM. Factors significantly predicting the use of CAM were female gender (OR, 95%CI, 1.71, 1.30-2.45), older age, steroids (1.49, 1.29-1.72), adverse events (1.43, 1.26-1.63), radiographic damage (1.40, 1.21-1.62), regular exercise (1.35, 1.19-1.53), surgery (1.31, 1.10-1.55), high income (1.30, 1.06-1.60), and high DAS28 (1.07, 1.07-1.15). Conclusions Patients with higher disease activity and lower health-related quality of life and higher functional disability used CAM significantly more frequently. Acknowledgements This study is supported by a grant from the Korea Healthcare Technology R&D Project, Ministry of Health and Welfare, Republic of Korea (A102065). Disclosure of Interest None Declared

AB0213 Treatment and outcomes of rheumatoid arthritis patients with hepatitis b

Background Treatment of rheumatoid arthritis (RA) patients with hepatitis B carries risk for reactivation of hepatitis B and drug-related hepatotoxicity. Objectives We investigated the impact of treatment for RA in patients with hepatitis B. Methods Patients enrolled in KORONA (Korean Observational Study Network for Arthritis) with 1-year follow up assessment with data on hepatitis B surface antigen (HBsAg) and hepatitis B core antibody (HBcAb) status were included in the analysis. Patient characteristics (age, sex, disease duration, delay in diagnosis, alcohol intake), disease outcome measures (DAS28, fatigue, sleep, HAQ, EQ-5D, radiographic damage, surgery), medications, and adverse events were assessed. Multiple logistic regression was used to analyze the predicting factors for liver function abnormalities. Results : A total of 871 patients were assessed. The number of HBsAg-positive and HBcAb-positive patients were 48 (5.5%) and 372 (42.7%), respectively. HBcAb-positive groups were significantly older (56.3 ± 10.8 vs 52.5 ± 9.0 in HBsAg-positive group and 51.3 ± 13.3 in negative group, p<0.01) and had longer disease duration (8.4 ± 7.7 vs 7.7 ± 6.0 in HBsAg-positive group and 7.8 ± 7.2 in negative-group, p=0.46). There was no significant difference in disease outcome measures between the groups, except for significantly increased radiographic damage in HBcAb group (79.6% vs 70.8% in HBsAg-positive group and 72.5% in negative group, p=0.048). Methotrexate and biologics use were significantly lower in HBsAg-positive group, while hydroxychloroquine, sulfasalazine, tacrolimus, and steroids use were significantly higher. HBsAg-positive group had significantly more adverse events (52.1%) compared to HBcAb-positive group (29.3%) and negative group (32.8%). HBsAg-positivity and HBcAb-positivity was not associated with significant increase in liver function abnormalities in the study population in multiple logistic regression analysis (OR (95%CI), 2.2 (0.7-7.4) and 0.8 (0.4-1.7), respectively). Conclusions HBsAg-positive patients were more frequently treated with steroids and less with methotrexate, but there was no significant difference in disease outcome. HBsAg-positive patients had more adverse events, but it did not show significant association with developing liver function abnormality. Acknowledgements This study is supported by a grant from the Korea Healthcare Technology R&D Project, Ministry of Health and Welfare, Republic of Korea (A102065). Disclosure of Interest None Declared

THU0139 Impacts of Immediate Changes in Dmards on Outcomes in Rheumatoid Arthritis with Moderate-to-Severe Activity

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

AB0214 Hypertension and its influence on cardiovascular risk and ra outcomes

Background Patients with rheumatoid arthritis (RA) are at increased risk for cardiovascular diseases (CVD). RA disease activity and inflammation contributes to the increase in risk, but traditional risk factor such as hypertension and dyslipidemia also plays a significant role. Objectives We investigated the influence of hypertension and its management on cardiovascular risk and RA-related outcomes in patients with RA. Methods RA patients from the KORONA (Korean Observational Study Network for Arthritis) prospective multicenter cohort were assessed for demographic factors, RA-related outcomes (DAS28, HAQ, EQ-5D), traditional risk factors for CVD, and cardiovascular risks. Systemic Coronary Risk Evaluation (SCORE) risk score and Korean 10-year CVD risk score were used to assess the CVD risk. Patients with no hypertension and those with either diagnosis of hypertension or high blood pressure were compared. Among the hypertension group, patients with blood pressure below the target (140/90mmHg) and those above the target were compared. Patients with no hypertension and those with hypertension and blood pressure below target with treatment were also compared. Results From the 5,376 patients enrolled in KORONA, 4,232 patients were included in the analysis after excluding 1,144 patients with missing information on cholesterol, smoking status, or blood pressure. Patients with hypertension or had high blood pressure were significantly younger (p<0.01), had longer disease duration (p<0.01), longer delay in diagnosis (p<0.01), higher HAQ score (p<0.01), lower EQ-5D score (p<0.01), higher disease activity (p<0.01), higher BMI (p<0.01), and more dyslipidemia (p<0.01). SCORE risk as well as the Korean 10-year CVD risk score were significantly higher in patients with hypertension and high blood pressure (p<0.01). Among the patients with hypertension, those still showing blood pressure above the target were older (p=0.47), had shorter disease duration (p=0.01), and higher SCORE risk (p<0.01) and Korean 10-year CVD risk score. When patients with no hypertension and those with hypertension but blood pressure below target with treatment were compared, patients with being treated for hypertension had higher HAQ score (p<0.01), lower EQ-5D score (p<0.01), higher disease activity (p<0.01), higher BMI (p<0.01), higher SCORE risk (p<0.01) and Korean 10-year CVD risk (p<0.01), and more dyslipidemia (p<0.01). Conclusions Patient with hypertension are at increased risk for CVD and the risk remained higher than the patients with no hypertension even after reaching the recommended target for blood pressure control. Acknowledgements This study is supported by a grant from the Korea Healthcare Technology R&D Project, Ministry of Health and Welfare, Republic of Korea (A102065). Disclosure of Interest None Declared