Sung Won Lee

Korean Observational Study Network for Arthritis (KORONA): Establishment of a Prospective Multicenter Cohort for Rheumatoid Arthritis in South Korea

OBJECTIVESnThe object of this study was to introduce the KORean Observational study Network for Arthritis (KORONA) registry with an emphasis on the design of the Korean rheumatoid arthritis (RA) national database, as well as to provide an overview of the RA patients who are currently registered in KORONA.nnnMETHODSnThe KORONA was established in July 2009 by the Clinical Research Center for Rheumatoid Arthritis (CRCRA) in South Korea. KORONA is based on a prospective protocol and standard, defined data collection instruments. Demographic and clinical features, laboratory and radiologic data, health-related outcomes, treatment side effects, resource utilization, and health behaviors of the RA cohort patients are recorded in a database.nnnRESULTSnA total of 23 institutions, which are about 38% of the rheumatologic departments at tertiary academic hospitals across South Korea, are part of KORONA. The quality control of data collection and management has been performed through annual monitoring and auditing, staff training, and providing standard operation protocol by the executive committee of CRCRA. As of 31 December 2010, 4721 patients with established RA were included in KORONA, because an annual survey had started to be performed in July 2010.nnnCONCLUSIONSnKORONA is the first nationwide Korean RA-specific cohort and it will provide valuable real-world information for Korean RA patients.

Do patients with elderly-onset rheumatoid arthritis have severe functional disability?

OBJECTIVEnTo identify the clinical features of elderly-onset rheumatoid arthritis (EORA) and their impact on disease outcome.nnnMETHODSnA total of 3169 rheumatoid arthritis (RA) patients were recruited as part of the Korean Observational Study Network for Arthritis, the nationwide cohort of South Korea. Patients were stratified according to age at disease onset: <40 years (younger age-onset RA, n = 1167), between the ages of 40 and 59 (middle-aged-onset RA, n = 1516), and ≥60 years (EORA, n = 486). To evaluate the significance of differences in clinical features among these 3 groups, we performed analysis of variance (anova) and the χ(2) test. We used multivariable logistic regression analysis to examine the association of onset age with functional disability measured with Health Assessment Questionnaire-Disability Index (HAQDI).nnnRESULTSnEORA patients were associated with high HAQDI (≥1) in bivariable analysis [odds ratio (OR) 1.36, confidence interval (CI) 1.04-1.77]. However, in multivariable analysis, not elderly onset but patients age, female gender, high disease activity, disease duration over 10 years, and comorbidity with cardiovascular disease were associated with high HAQDI. Only in a predefined subgroup with disease duration <10 years, elderly onset was an independent influencing factor for the functional disability of RA patients (OR 3.04, CI 1.85-5.67: disease duration of <5 years, OR 3.07, CI 1.64-5.74: disease duration of 5 to 10 years).nnnCONCLUSIONSnDisease onset in older age was associated independently with functional disability of RA patients who have relatively short disease duration.

Mapping health assessment questionnaire disability index (HAQ-DI) score, pain visual analog scale (VAS), and disease activity score in 28 joints (DAS28) onto the EuroQol-5D (EQ-5D) utility score with the KORean Observational study Network for Arthritis (KORONA) registry data.

Abstract The aim of this study was to estimate the mapping model for EuroQol-5D (EQ-5D) utility values using the health assessment questionnaire disability index (HAQ-DI), pain visual analog scale (VAS), and disease activity score in 28 joints (DAS28) in a large, nationwide cohort of rheumatoid arthritis (RA) patients in Korea. The KORean Observational study Network for Arthritis (KORONA) registry data on 3557 patients with RA were used. Data were randomly divided into a modeling set (80xa0% of the data) and a validation set (20xa0% of the data). The ordinary least squares (OLS), Tobit, and two-part model methods were employed to construct a model to map to the EQ-5D index. Using a combination of HAQ-DI, pain VAS, and DAS28, four model versions were examined. To evaluate the predictive accuracy of the models, the root-mean-square error (RMSE) and mean absolute error (MAE) were calculated using the validation dataset. A model that included HAQ-DI, pain VAS, and DAS28 produced the highest adjusted R2 as well as the lowest Akaike information criterion, RMSE, and MAE, regardless of the statistical methods used in modeling set. The mapping equation of the OLS method is given as EQ-5Dxa0=xa00.95−0.21xa0×xa0HAQ-DI−0.24xa0×xa0pain VAS/100–0.01xa0×xa0DAS28 (adjusted R2xa0=xa057.6xa0%, RMSExa0=xa00.1654 and MAExa0=xa00.1222). Also in the validation set, the RMSE and MAE were shown to be the smallest. The model with HAQ-DI, pain VAS, and DAS28 showed the best performance, and this mapping model enabled the estimation of an EQ-5D value for RA patients in whom utility values have not been measured.

What factors affect discordance between physicians and patients in the global assessment of disease activity in rheumatoid arthritis

Abstract Objective: To identify the level of agreement between patients with rheumatoid arthritis (RA) and physicians in the global assessment of disease activity and to explore factors influencing their discordance. Methods: A total of 4368 patients with RA were analyzed from the KORean Observational study Network for Arthritis (KORONA) database. Patients were divided into four subgroups according to difference from their physicians in the assessment of disease activity by substracting physician’s visual analog scale (VAS) from patient’s VAS as follows: positive discordance group I (10u2009mmu2009≤u2009discordance <25u2009mm), positive discordance group II (≥25u2009mm), concordance (<|10| mm), and negative discordance (≤u2009−10mm). Multinomial logistic regression analysis was performed to identify factors associated with discordance. Results: Only 1350 (29.2%) patients were classified in the concordance group. Positive discordance was found in 52.3% of the patients (nu2009=u20092425), with 33.7% (nu2009=u20091563) showing marked discordance (≥25u2009mm). The high disease activity (OR =1.41), gastrointestinal (GI) disease (OR =1.28), pain (OR =1.12), fatigue (OR =1.07) were consistently associated with positive discordance. Conclusion: More than half of patients with RA thought their disease more severe than their physicians. In addition to high disease activity, pain, fatigue, and sleep disturbance or GI disease were associated with the discordance between physicians and patients with RA.

Severe inflammation may be caused by hyperferritinemia of pseudo-pseudo Meigs' syndrome in lupus patients: two cases reports and a literature review

Pseudo-pseudo Meigs syndrome or Tjalma syndrome is a rare manifestation of patients with systemic lupus erythematosus defined by the presence of ascites, pleural effusions, and an elevated cancer antigen 125 level. In this case, we described a patient with lupus who presented with sudden impaired renal function and subsequent development of massive ascites with marked high serum ferritin. Hyperferritinemia is one of the abnormal laboratory findings in severe inflammation with ferritin functioning as an inflammatory marker. However, its correlation with lupus activity remains unclear. Therefore, a review of the literature regarding pseudo-pseudo Meigs syndrome associated with lupus and high ferritin level in this disease was carried out.

Comparative effectiveness of treatment options after conventional DMARDs failure in rheumatoid arthritis

ObjectiveTo compare the clinical effectiveness of two treatment strategies for active rheumatoid arthritis (RA) refractory to conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs): starting TNF inhibitors (TNFIs) or changing csDMARDs.MethodsWe used two nationwide Korean RA registries for patient selection. TNFI users were selected from the BIOPSY, which is an inception cohort of RA patients starting biologic DMARDs. As a control group, we selected RA patients with moderate or high disease activity from the KORONA database whose treatment was changed to other csDMARDs. After comparing baseline characteristics between the two groups in either unmatched or propensity score matched cohorts, we compared potential differences in the 1-year remission rate as a primary outcome and changes in HAQ-DI and EQ-5D scores as secondary outcomes.ResultsA total of 356 TNFI starters and 586 csDMARD changers were identified from each registry as unmatched cohorts, and 294 patients were included in the propensity score matched cohort. In the intention-to-treat analysis, TNFI starters had higher 1-year remission rates than csDMARD changers in both unmatched (19.1 vs. 18.4%, pu2009<u20090.01) and matched cohorts (19.7 vs. 15.0%, pu2009<u20090.01). In per protocol analysis, TNFI starters had much higher remission rates in unmatched (37.2 vs. 28.0%, pu2009=u20090.04) and matched cohorts (35.4 vs. 19.1%, pu2009=u20090.04). However, in matched cohorts, no significant differences were observed between two groups in HAQ-DI and EQ-5D scores.ConclusionsWe compared the clinical effectiveness of the two treatment strategies for active RA refractory to csDMARDs. TNFI starters showed higher 1-year remission rates than csDMARD changers.

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.

Jejunal vasculitis in patient with rheumatoid arthritis: case report and literature review

A 57-year-old man with rheumatoid arthritis presented severe abdominal pain symptomatic of panperitonitis. Computer tomography findings were consistent with vasculitis on the jejunum. Confirmatory angiography was conducted. Since abdominal vasculitis in rheumatoid arthritis is very rare, early diagnosis and treatment should be done according to clinical manifestation. In this case, high-dose steroid treatment was applied based on clinical manifestation, laboratory findings, and radiologic finding. After therapy, clinical manifestation and flare-up arthritis diminished.

Impact of early diagnosis on functional disability in rheumatoid arthritis

Background/Aims To determine whether early diagnosis is beneficial for functional status of various disease durations in rheumatoid arthritis (RA) patients. Methods A total of 4,540 RA patients were enrolled as part of the Korean Observational Study Network for Arthritis (KORONA). We defined early diagnosis as a lag time between symptom onset and RA diagnosis of ≤ 12 months, whereas patients with a longer lag time comprised the delayed diagnosis group. Demographic characteristics and outcomes were compared between early and delayed diagnosis groups. Logistic regression analyses were performed to identify the impact of early diagnosis on the development of functional disability in RA patients. Results A total of 2,597 patients (57.2%) were included in the early diagnosis group. The average Health Assessment Questionnaire-Disability Index (HAQ-DI) score was higher in the delayed diagnosis group (0.64 ± 0.63 vs. 0.70 ± 0.66, p < 0.01), and the proportion of patients with no functional disability (HAQ = 0) was higher in the early diagnosis group (22.9% vs. 20.0%, p = 0.02). In multivariable analyses, early diagnosis was independently associated with no functional disability (odds ratio [OR], 1.19; 95% confidence interval [CI], 1.01 to 1.40). In a subgroup analysis according to disease duration, early diagnosis was associated with no functional disability in patients with disease duration < 5 years (OR, 1.37; 95% CI, 1.09 to 1.72) but not in patients with longer disease duration (for 5 to 10 years: OR, 1.07; 95% CI, 0.75 to 1.52; for ≥ 10 years: OR, 0.92; 95% CI, 0.65 to 1.28). Conclusions Early diagnosis is associated with no functional disability, especially in patients with shorter disease duration.

AB0107 The modulation of macrophage polarization by sirt1 maybe new target therapy in rheumatoid arthritis

Background The polarization of macrophages was the expressed to M1/M2 phenotype by various stimuli or environment signals. The M1 macrophage was pro-inflammatory phenotype and was key effector cells in the immune response of rheumatoid arthritis (RA). So, M1 macrophage influenced the inflammation of RA synovial membrane and joint destruction in RA, whereas M2 macrophage was anti-inflammatory phenotype and could down-regulate the production of proinflammatory cytokines in RA. The SIRT1 attenuated the RA inflammation via down-regulation of NF-κB signaling. However, the effect of SIRT1 on macrophages polarization remained uncler. Objectives We aimed to check out that activated SIRT1 modulated macrophages polarization into M1 phenotype and controlled the inflammation of RA. Methods Monocytes from synovial fluid of RA patients, bone marrow–derived monocytes (BMDCs) from mice were studied. monocytes were cultured with M-CSF for 7days to differentiate into M0 macrophages (monocyte-derived mature macrophages M0 phenotype). M0 macrophages were incubated with LPS and IFN-gamma in order to obtain M1 macrophages. M1 macrophage markers were detected by real-time PCR. Results Activation of SIRT1 was achieved by Resveratrol, activated SIRT1 attenuated M1 macrophage phenotypes and pro-inflammatory cytokine expression. macrophages obtained from SIRT1-tg mice, which were overexpression of SIRT1, exhibited decreased M1 markers in association with enhanced activation of AMPK/ACC compared with macrophage from control C57BL/6 mice. In addition to SIRT1 activation, M1 polarizing signal, acetylation of NF-κB p65, was suppressed. In SIRT1-deficient macrophages, resveratrol fail to increase AMPK activity and to decrease the expression M1 markers owing to enhanced acetylation of NF-κB p65. Conclusions SIRT1 maybe an important modulator of M1 macrophages polarization and increased AMPK activity, which suppressed acetylation of NF-κB p65 during inflammation of RA. so, modulation of SIRT1 maybe a new target in RA treatment. References SIRT1 inhibits differentiation of monocytes to macrophages: amelioration of synovial inflammation in rheumatoid arthritis. J Mol Med (Berl). 2016 Aug;94(8):921–31. Disclosure of Interest None declared