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BackgroundThis study aimed to classify the distinct group of patients with axial spondyloarthritis (SpA) on tumour necrosis factor alpha inhibitors (TNFi) according to the baseline characteristics using a clustering algorithm.MethodsThe clinical characteristics and demographic data of patients with axial SpA included in the Korean College of Rheumatology Biologics and Targeted Therapy registry were investigated. The patterns of disease manifestations were examined using divisive hierarchical cluster analysis. After clustering, we compared the clinical characteristics of patients and the drug survival of TNFi between the classified groups.ResultsA total of 1042 patients were analysed. The cluster analysis classified patients into two groups: axial group predominantly showing isolated axial manifestations (n= 828) and extra-axial group more frequently showing extra-axial symptoms (n= 214). Almost all extra-axial symptoms (peripheral arthritis, enthesitis, uveitis, and psoriasis) were more frequently observed in the extra-axial group than in the axial group. Moreover, patients in the extra-axial group had shorter disease duration, later disease onset, and higher disease activity than those in the axial group. The disease activity was comparable between the two groups after 1 year of treatment with TNFi. Interestingly, the extra-axial group had a lower drug survival with TNFi than the axial group (p= 0.001).ConclusionsCluster analysis of patients with axial SpA using TNFi classified two distinct clinical phenotypes. These clusters had different TNFi drug survival, clinical characteristics, and disease activity.

AIM To evaluate clinical characteristics and natural history of non-radiographic axial spondyloarthritis (nr-axSpA) using KOrean Nonradiographic Axial SPondyloArthritis (KONASPA) data. METHODS Data were collected from 11 centers in South Korea. A total of 278 patients with nr-axSpA from January 2018 to July 2020 were included. Demographic data, clinical features, comorbidities, disease activity, medications, and laboratory results were collected. RESULTS Mean age at symptom onset was 28.2 ± 14.2 years. Of 278 patients, 152 (54.7%) were male. Mean Bath Ankylosing Spondylitis Disease Activity Index at diagnosis was 3.5 ± 2.1. Dyslipidemia was the most common comorbidity (8.4%), followed by hypertension (6.1%). Mean age at diagnosis of nr-axSpA was older in female patients than in male patients (31.8 ± 15.8 years vs 24.9 ± 12.0 years, P

Objective. Ankylosing spondylitis (AS) is a chronic inflammatory disease with obvious male preponderance. Males show more severe radiographic manifestations compared with females. This study aimed to evaluate the effects of sex and estrogen on the radiographic progression of AS. Methods. A total of 101 patients with AS were included in this study. All of the radiographs were scored using the modified Stoke AS Spine Score (mSASSS). Serum levels of 17β-estradiol (E2), dickkopf-1 (Dkk1), and leptin were detected by enzyme-linked immunosorbent assay. The generalized estimating equations model was used to evaluate factors associated with spinal radiographic progression. Results. The mean age at disease onset was 27.3±10.7 years, and 16 patients (15.8%) were female. In the multivariable analysis, body mass index (β-coefficient=0.12; p=0.047) and levels of Dkk1 (β-coefficient=-0.11; p＜0.001), and female (β-coefficient=-1.40; p=0.001) were associated with radiographic progression. Among male patients with AS, baseline C-reactive protein (β=0.11; p=0.005) and mSASSS (β=0.21; p=0.030) were also associated with radiographic progression. E2 and leptin levels were not significantly related to the radiographic progression. Conclusion. Although female patients were associated with less radiographic progression in AS, there was no significant relationship between serum estrogen level and radiographic progression. Results of current study suggests that genetic factors or other environmental factors associated with female may influence radiographic progression in patients with AS. (J Rheum Dis 2021;28:76-84)

Ankylosing spondylitis is a male-predominant disease and previous study revealed that estrogens have an anti-inflammatory effect on the spondyloarthritis (SpA) manifestations in zymosan-induced SKG mice. This study aimed to evaluate the effect of selective estrogen receptor modulator (SERM) lasofoxifene (Laso) on disease activity of SpA. Mice were randomized into zymosan-treated, zymosan + 17β-estradiol (E2)-treated, and zymosan + Laso-treated groups. Arthritis was assessed by 18F-fluorodeoxyglucose (18F-FDG) small-animal positron emission tomography/computed tomography and bone mineral density (BMD) was measured. Fecal samples were collected and 16S ribosomal RNA gene sequencing was used to determine gut microbiota differences. Both zymosan + E2-treated mice and zymosan + Laso-treated mice showed lower arthritis clinical scores and lower 18F-FDG uptake than zymosan-treated mice. BMD was significantly higher in zymosan + E2-treated mice and zymosan + Laso-treated mice than zymosan-treated mice, respectively. Fecal calprotectin levels were significantly elevated at 8 weeks after zymosan injection in zymosan-treated mice, but it was not significantly changed in zymosan + E2-treated mice and zymosan + Laso-treated mice. Gut microbiota diversity of zymosan-treated mice was significantly different from zymosan + E2-treated mice and zymosan + Laso-treated mice, respectively. There was no significant difference in gut microbiota diversity between zymosan + E2-treated mice and zymosan + Laso -treated mice. Laso inhibited joint inflammation and enhanced BMD in SKG mice, a model of SpA. Laso also affected the composition and biodiversity of gut microbiota. This study provides new knowledge regarding that selected SpA patients could benefit from SERM treatment.

Background Patient-centered management is becoming increasingly important in gout, but there are limited studies exploring patients' perspectives and preferences. We aimed to investigate patients' perspectives and preferences regarding gout and gout management, and their impacts on adherence to urate lowering therapy (ULT). Methods A paper-based survey was performed in patients with gout seen at the rheumatology outpatient clinics of 16 tertiary hospitals. The survey included questions regarding demographics, comorbidities, gout attacks, current treatment and adherence, and patients' perspectives and preferences regarding gout and gout management. Multivariate regression analysis was performed to determine the factors associated with ULT adherence. Results Of 809 surveyed patients with gout, 755 (94.5%) were using ULT. Among those using ULT, 89.1% had ≥ 80% adherence to ULT. Majority of the patients knew management strategies to some extent (94.8%), perceived gout as a life-long disease (91.2%), and were making efforts toward practicing at least one lifestyle modification (89.2%). Most patients (71.9%) obtained information about gout management during their clinic visits. Approximately half of the patients (53.6%) preferred managing their disease with both ULT and lifestyle modification, 28.4% preferred ULT only, and 17.4% preferred lifestyle modification only. Adherence was better in patients with older age (odds ratio [OR], 1.03), those with better knowledge of gout management strategies (OR, 3.56), and those who had preference for ULT (OR, 2.07). Conclusion Patients' perspectives and management preferences had high impacts on adherence to ULT in gout. Consideration of patients' perspectives and preferences is important for achieving the desired clinical outcome in gout., Graphical Abstract

Background/objectives Gout and hyperuricemia incidence is increasing worldwide, reflecting pandemic overweight and obesity. However, the magnitude of the association of body mass index (BMI) changes with serum uric acid (SUA) level in the general population has remained unevaluated. Methods This retrospective cohort study enrolled 27,422 Korean men who underwent comprehensive health checkup between 2015 and 2017. BMI change was categorized into seven groups. The relationship between BMI change and SUA level alteration was determined using multivariable regression models. Results The mean age, BMI, and SUA were 38.8 years, 24.7 kg/m2 , and 6.2 mg/dl. All BMI change categories had a clear dose-response relationship with the SUA level changes. The corresponding beta-coefficient of SUA level changes was 0.13 (0.11, 0.16), 0.25 (0.2, 0.3), and 0.44 (0.36, 0.52) for a BMI decrease of 0.5-1.5, 1.5-2.5, and ≥2.5, respectively. Compared with no BMI change, the multivariate odds ratios of achieving normouricemia for a BMI increase of 0.5-1.5, 1.5-2.5, and ≥2.5 were 0.88 (95% CI: 0.83, 0.95), 0.67 (0.60, 0.75), and 0.60 (0.49, 0.74), whereas those for a BMI decrease of 0.5-1.5, 1.5-2.5, and ≥2.5 were 1.17 (1.07, 1.27), 1.28 (1.08, 1.52), and 1.46 (1.13, 1.88), respectively. Conclusions BMI change could have a significant association with the alteration of SUA levels of apparently healthy men. Despite its small effect size, the health risks and benefits of BMI change would be emphasized for the SUA level alteration.

Background and objectives: Hyperuricemia is one of the well-known cardiovascular risk factors. There is a growing interest in the association between hyperuricemia and arrhythmia. We used the representative sample data of Korean population to study the association between hyperuricemia and heart rate irregularity (HRI) that reflects total arrhythmia. Materials and Methods: We performed weighted multivariate logistic regression analysis to assess the association between hyperuricemia and HRI. Results: Of the 10,827 subjects, 1308 (13.2%) had hyperuricemia and 130 (1%) had HRI. In the presence of hyperuricemia, HRI was three times higher than that in the absence of hyperuricemia (OR 2.98, 95% CI 1.71&ndash, 5.18). The risk of HRI was highest in subjects with both hypertension and hyperuricemia. In the subgroup analysis, the association of hyperuricemia with HRI was most pronounced in the smoker group. Conclusions: Hyperuricemia was highly correlated with HRI in adult Korean representative sample data. Hyperuricemia was associated with a nearly tripled risk for HRI. Hypertension has a synergistic effect with hyperuricemia on HRI. Further research is warranted to clarify the relationship between hyperuricemia and arrhythmia and its mechanism.

Background/Aims: The objective of this study was to compare changes in the simplified disease activity index (SDAI) between biologic (b) and conventional (c) disease-modifying antirheumatic drugs (DMARD) users with seropositive rheu matoid arthritis (RA) in daily clinical practice. Methods: This was a nationwide multicenter observational study. Patients who had three or more active joint counts and abnormal inf lammatory marker in blood test were enrolled. The selection of DMARDs was determined by the attending rheumatologist. Clinical parameters, laboratory findings, and Health Assessment Questionnaire (HAQ) scores were obtained at baseline and at 6 and 12 months. Se rial SDAI changes and clinical remission rate at 6 and 12 months were assessed. Results: A total of 850 patients participated in this study. The mean baseline SDAI score in bDMARD group was higher than that in cDMARD group (32.08 ± 12.98 vs 25.69 ± 10.97, p < 0.0001). Mean change of SDAI at 12 months was -19.0 in the bDMARD group and -12.6 in the cDMARD group (p < 0.0001). Clinical remission rates at 12 months in bDMARD and cDMARD groups were 15.4% and 14.6%, re spectively. Patient global assessment and HAQ at 12 months were also significantly improved in both groups. Multivariate logistic regression showed that baseline HAQ score was the most notable factor associated with remission. Conclusions: There was a significant reduction in SDAI within 12 months after receiving DMARDs in Korean seropositive RA patients irrespective of bDMARD or cDMARD use in real-world practice. Clinical remission was achieved in those with lower baseline HAQ scores.

PURPOSE To evaluate changes in the peripapillary retinal nerve fiber layer (RNFL) thicknesses using spectral-domain optical coherence tomography (SD-OCT) in hydroxychloroquine (HCQ) users. METHODS The medical records of HCQ users were retrospectively reviewed. In these HCQ users, an automated perimetry, fundus autofluorescence photography, and SD-OCT with peripapillary RNFL thickness measurements were performed. The peripapillary RNFL thicknesses were compared between the HCQ users and the control groups. The relationships between the RNFL thicknesses and the duration or cumulative dosage of HCQ use were analyzed. RESULTS This study included 77 HCQ users and 20 normal controls. The mean duration of HCQ usage was 63.6 ± 38.4 months, and the cumulative dose of HCQ was 528.1 ± 3.44 g. Six patients developed HCQ retinopathy. Global and six sectoral RNFL thicknesses of the HCQ users did not significantly decrease compared to those of the normal controls. No significant correlation was found between the RNFL thickness and the duration of use or cumulative dose. The eyes of those with HCQ retinopathy had temporal peripapillary RNFL thicknesses significantly greater than that of normal controls. CONCLUSIONS The peripapillary RNFL thicknesses did not change in the HCQ users and did not correlate with the duration of HCQ use or cumulative doses of HCQ. RNFL thickness is not a useful biomarker for the early detection of HCQ retinal toxicity.

BACKGROUND/AIMS The objective of this study was to determine the efficacy and safety of add-on therapy with certolizumab pegol (CZP) in active rheumatoid arthritis (RA) patients of a single ethnicity. METHODS In this 24-week, phase 3, randomized, double-blind, placebo-controlled trial, eligible patients (n = 127) were randomized 2:1 to subcutaneous CZP + methotrexate (MTX; 400 mg at week 0, 2, and 4 followed by 200 mg every 2 weeks) or placebo + MTX. RESULTS At week 24, the American College of Rheumatology criteria for 20% (ACR20) response rate was significantly greater with CZP + MTX than with placebo (66.7% vs. 27.5%, p < 0.001). Differences in ACR20 response rates for CZP vs. placebo were significant from week 1 (p < 0.05) and remained significant through week 24. The CZP group reported significant improvement in physical function and disability compared to the placebo group (p < 0.001) at week 24, as assessed by Korean Health Assessment Questionnaire-Disability Index (KHAQ-DI). Post hoc analysis indicated that the proportion of patients who had ACR70 responses, Disease Activity Score 28 (DAS28) low disease activity, and DAS28 remission at week 24 was greater in CZP + MTX-treated patients who achieved a decrease in DAS28 ≥ 1.2 (43.8%) at week 4 than in nonresponders. Among 18 (22.2%) and 14 patients (35.0%) in CZP and placebo groups who had latent tuberculosis (TB), none developed active TB. Most adverse events were mild or moderate. CONCLUSION CZP treatment combined with MTX in active RA patients with moderate to severe disease activity and an inadequate response to MTX resulted in rapid onset of efficacy, which is associated with better clinical outcome at week 24 and has an acceptable safety profile, especially in an intermediate TB-burden population.

Aim To evaluate the effect of tumor necrosis factor α inhibitors (TNFi) on spinal radiographic progression in patients with ankylosing spondylitis (AS). Methods Subjects were selected from patients at a single tertiary hospital between 1995 and 2014. Patients who used TNFi with baseline and paired follow-up radiographic data with a minimum interval of 2 years were included. Time to start TNFi was defined as the time from symptom onset to the start of TNFi use. TNFi index was defined as the ratio of the period of TNFi use to the entire period of disease. Radiographic damage was assessed by the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS). Univariable and multivariable linear regression analyses were used to identify factors associated with radiographic progression. Results A total of 151 patients were included in the analysis. Seventeen (11.3%) patients were female and mean ΔmSASSS/year was 1.01 units/year. Mean X-ray follow-up duration was 102.9 ± 54.9 months. Mean time from symptom onset to start of TNFi use was 104.8 ± 83.6 months (median 84 months) and mean TNFi index was 42.9 ± 23.8% (median 40.9%). In multivariable analysis, initial mSASSS, initial C-reactive protein, body mass index, current smoker, and delayed start of TNFi use were associated with radiographic progression. Presence of peripheral arthritis and the TNFi index were negatively associated with radiographic progression. Conclusions A delay in starting TNFi use and low TNFi index were associated with radiographic progression. Early and long-term use of TNFi appear to reduce spinal radiographic progression in patients with AS.

Background/aims To evaluate drug survival of the tumor necrosis factor α inhibitors (TNFi) and risk factors for the drug discontinuation in patients with ankylosing spondylitis (AS). Methods We retrospectively evaluated 487 AS patients at a single tertiary hospital. Among the TNFi users, drug survival and risk factors of TNFi discontinuation were investigated. Results Among 487 patients, 128 AS patients were treated with at least one TNFi. Patients who were treated with TNFi were younger at disease onset, had more peripheral manifestations, and had higher level of acute phase reactants and body mass index than those of TNFi non-users at baseline. Of 128 patients, 28 patients (21.9%) discontinued first TNFi therapy during the follow-up period of 65.1 ± 27.9 months. In the multivariable analysis, female (hazard ratio [HR], 6.08; 95% confidence interval [CI], 2.27 to 16.27; p = 0.003), hip involvement (HR, 2.52; 95% CI, 1.08 to 5.87; p = 0.033) and a high C-reactive protein (CRP; HR, 1.10; 95% CI, 1.00 to 1.21; p = 0.044) were risk factors for drug discontinuation. Etanercept showed better survival rate than infliximab. The main reason for discontinuation of TNFi was inefficacy. Conclusions TNFi discontinuation rate of Korean patients with AS seems to be similar to those with the European patients. Female sex, hip involvement, CRP, and the type of TNFi were associated with TNFi discontinuation.

Osteopoikilosis is an autosomal dominant bone disorder characterized by symmetric multiple osteosclerotic lesions throughout the axial and appendicular skeleton. Pathogenic variants in the LEMD3 have been identified as the cause of osteopoikilosis. LEMD3 encodes an inner nuclear membrane protein that interacts with bone morphogenetic protein (BMP) and transforming growth factor (TGF)-β pathways. We report the case of a 19-year-old man presenting with lower back pain and sciatica. His radiograph revealed bilateral and symmetrical multiple osteosclerotic bone lesions in both scapular areas. Sanger sequencing of LEMD3 revealed a four-base-pair deletion in intron 2 (c.1560+5_1560+8del), [corrected] which was inherited from his father. We found that this four-base-pair deletion in intron 2 causes aberrant splicing and consequent deletion of exon 2. To the best of our knowledge, this is the first report of genetically confirmed osteopoikilosis in Korea.

Objectives To estimate the prevalence of impaired morning function (IMF) in rheumatoid arthritis (RA), and to understand physicians’ and patients’ perceptions on the impact of IMF and treatment in selected Asian countries. Methods A survey on the impact of IMF was conducted in Asia on rheumatologists and patients with moderate-to-severe RA who experienced IMF for ≥3 mornings a week. Participants underwent comprehensive face-to-face interviews using structured questionnaires. Results Sixty physicians and 300 patients from Hong Kong, Philippines, Singapore, South Korea, and Taiwan were surveyed. Rheumatologists estimated that two-thirds of patients with RA experienced IMF and believed that the prevalence of IMF increased with RA severity (present in 42%, 73%, and 87% of patients with mild, moderate, and severe disease, respectively). Patients’ survey revealed that, on an average, patients with RA experienced IMF 5 days a week for 2 h each day. Thirty-eight percent of patients with RA considered a reduction in morning stiffness as an important treatment goal, but this was agreed by only 3% of rheumatologists. Only 22% of rheumatologists modified the treatment regimen specifically for IMF. Physicians considered prednisolone and other glucocorticoids (GCs) to be the most effective medication for the treatment of IMF. Fifty-one percent of patients with RA did not find their current medication effective in relieving IMF, and as a result, they reported negative emotions such as frustration, defeat, and anger, and 56% had missed work because of this symptom. Conclusions IMF is prevalent in RA and significantly affects patients’ quality of life (QoL). A higher proportion of patients compared to physicians view the reduction of morning stiffness as an important goal. More should be done to address the dissonance between physicians’ and patients’ views on IMF.

Hyperuricemia and anemia share several comorbidities, but the association between the two conditions remains unclear. The purpose of this study was to investigate the association between hyperuricemia and anemia. Data of 10794 subjects from the Korean National Health and Nutrition Examination Survey conducted in 2016–2017 were analyzed using multivariate logistic regression analyses. An association between anemia and hyperuricemia was not evident in subjects without chronic kidney disease (CKD). In patients with CKD, anemia increased the risk of hyperuricemia by 2-fold. This association remained significant when adjusting for the glomerular filtration rate. In subgroup analyses, the association of anemia with hyperuricemia was significant in subjects aged ≥65 years, and in those with diabetes or hypertension. Subgroup analyses of CKD patients showed similar results. In the current study using data from Korean representative samples, anemia in subjects with CKD was associated with a 2-fold increase in the risk of hyperuricemia, which remained significant even after adjustment for renal function.

We investigated risk factors for immune-related adverse events (irAEs) in patients treated with anti-programmed cell death protein1 antibody pembrolizumab. A retrospective medical record review was performed to identify all patients who received at least one dose of pembrolizumab at Samsung Medical Center, Seoul, Korea between June 2015 and December 2017. Three hundred and ninety-one patients were included in the study. Data were collected on baseline characteristics, treatment details, and adverse events. Univariate and multivariate logistic regression models were used to identify risk factors for irAEs. Sixty-seven (17.1%) patients experienced clinically significant irAEs; most commonly dermatologic disorders, followed by pneumonitis, musculoskeletal disorders, and endocrine disorders. Fourteen patients (3.6%) experienced serious irAEs (grade ≥ 3). Most common serious irAEs were pneumonitis (2.3%). Four deaths were associated with irAEs, all of which were due to pneumonitis. In multivariate regression analysis, a higher body mass index (BMI) and multiple cycles of pembrolizumab were associated with higher risk of irAEs (BMI: odds ratio [OR] 1.08, 95% confidence interval [CI] 1.01–1.16; pembrolizumab cycle: OR 1.15, 95% CI 1.08–1.22). A derived neutrophil-lymphocyte ratio (dNLR) greater than 3 at baseline was correlated with low risk of irAEs (OR 0.37, 95% CI 0.17–0.81). Our study demonstrated that an elevated BMI and higher number of cycles of pembrolizumab were associated with an increased risk of irAEs in patients treated with pembrolizumab. Additionally, increased dNLR at baseline was negatively correlated with the risk of developing irAEs.

Background: Hyperuricemia and anemia may be related in terms of sharing comorbidities such as chronic kidney disease and cardiovascular disease. However, to our knowledge, no studies have been conducted on the relationship between two conditions. For the association of gout and anemia, there was a previous cohort study showing that patients with anemia had a 2-fold higher risk of gout compared to patients without anemia. And the risk of gout was significantly higher after adjusting for serum urate levels and kidney function. However, there is a lack of data on the relationship between anemia and hyperuricemia. Objectives: The purpose of this study was to investigate the association between hyperuricemia and anemia using data from Korean National Health and Nutrition Examination Survey (KNHANES VII; 2016), which is representative of the Korean population. Methods: The present study included 5887 participants aged ≥ 19 years from KNHANES VII. Logistic regression was used to examine the association between anemia and hyperuricemia. Subgroup analysis was performed to confirm whether the association between two conditions varies according to participant characteristics. Results: In an adjusted model that corrected for body mass index, smoking, drinking, physical activity, income, and education levels, hyperuricemia was 1.4 times more than that those without anemia (HR 1.41, 95% CI 1.01-1.98). The association of anemia with hyperuricemia was not seen under 65 years of age (HR 2.68, 95% CI 1.60-4.48). In addition, this association was not clear in women, but was significant in men (HR 2.62, 95% CI 1.47-4.70). In the results of subgroup analysis according to comorbidities, the association of anemia with hyperuricemia was significant only in subgroups with chronic kidney disease, diabetes, hypertension, metabolic syndrome, and cardiovascular diseases. There was no association between anemia and hyperuricemia in obese subjects, but hyperuricemia risk was higher in non-obese subjects with anemia compared to those who did not have anemia. Conclusion: In a Korean representative sample, the risk of hyperuricemia was higher for anemia. The association of anemia with hyperuricemia was more pronounced in subjects with older age, male population, and other comorbid conditions. Disclosure of Interests: None declared

Background: Hyperuricemia is one of the well-known cardiovascular risk factors. In recent studies, hyperuricemia has been shown to be an independent risk factor for atrial fibrillation, which may be associated with oxidative stress or inflammation. There is still a lack of data on the association of hyperuricemia and arrhythmia other than atrial fibrillation. Objectives: In this study, we investigated the relationship between hyperuricemia and heart rate (HR) irregularity using representative sample data of adult Korean. Methods: The study included 5870 subjects aged 19 years or older who completed the uric acid measurement in the Korean National Health and Nutrition Examination Survey conducted in 2016. Logistic regression was used to analyze the association between hyperuricemia and HR irregularity identified by the examiner at the time of the survey. Results: Subjects with HR irregularity were older, had more smoking and drinking, had a higher prevalence of HTN, and had lower glomerular filtration rate than those with regular heartbeat. In the presence of hyperuricemia, the HR irregularity was three times higher than in the absence (HR 3.65, 95% CI 1.77-7.53, P = 0.0005). The association of HR irregularity and hyperuricemia was significant in most subjects, especially in those older than 65 years, with diabetes and hypertension. Conclusion: Hyperuricemia was highly correlated with HR irregularity in adult Korean representative sample data, especially in subjects with conventional cardiovascular risk factors such as old age, hypertension, diabetes mellitus. This study included all subjects who showed HR irregularity at the time of examination, not just atrial fibrillation. Therefore, it is suggested that hyperuricemia may be associated with other arrhythmia as well as atrial fibrillation. Further researches are warranted to clarify the relationship between hyperuricemia and arrhythmia and its mechanism. Disclosure of Interests: None declared

Hyperuricemia is an emerging potential biomarker for metabolic syndrome (MetS) and its complications. This study aimed to investigate the risk factors of hyperuricemia, particularly, the association of hyperuricemia with MetS and general obesity according to sex. We performed multivariate logistic regression analyses using the 2016 Korean National Health and Nutrition Examination Survey data. Hyperuricemia was defined by a serum uric acid level &ge, 7.0 mg/dL for men and &ge, 6.0 mg/dL for women. General obesity was based on a body mass index (BMI) &ge, 25 kg/m2. Among a total of 5591 Korean adult participants, 685 (12.3%) individuals had hyperuricemia. Hyperuricemia was significantly associated with MetS in men (odds ratio (OR): 2.38, 95% CI: 1.84&ndash, 3.08) and in women (OR: 4.15, 95% CI: 2.75&ndash, 6.28) after adjustments. General obesity was also independently related to hyperuricemia in both sexes (OR: 2.17, 95% CI: 1.76&ndash, 2.68 in men, OR: 3.80, 95% CI: 2.82&ndash, 5.12 in women). In subgroup analyses, the presence of concomitant MetS and general obesity posed a strikingly higher risk for hyperuricemia among women (OR: 7.24, 95% CI: 4.56&ndash, 11.50) when compared to men (OR: 2.90, 95% CI: 2.12&ndash, 3.96). More attention should be paid to the increased risk of hyperuricemia for females with both MetS and general obesity.

Background: Hyperuricemia is emerging as a potential biomarker and a predictor for metabolic syndrome (MetS) and its related complications. Objectives: We aimed this study to investigate the risk factors of hyperuricemia, particularly, the association of hyperuricemia with MetS and general obesity. Methods: We performed multivariate logistic regression analyses using the 2016 Korea National Health and Nutrition Examination Survey (KNHANES) data collected in a representative sample of Korean adults. Hyperuricemia was defined by serum uric acid level ≥7.0 mg/dl for men and ≥6.0 mg/dl for women. General obesity was based on body mass index (BMI) ≥25 kg/m2. Results: Among a total of 5,591 Korean adult participants, 685 (12.3%) individuals were classified as having hyperuricemia. Hyperuricemia was significantly associated with MetS in men (Odd ratio (OR): 1.74, 95% CI: 1.29-2.34) and women (OR: 2.47, 95% CI: 1.55-3.93) after adjustments for age, sex, smoking, alcohol, exercise, BMI and estimated glomerular filtration rate (eGFR). General obesity was also independently related to hyperuricemia in both sex (OR: 1.70, 95% CI: 1.31-2.19 in men, OR: 3.73, 95% CI: 2.57-5.41 in women). Among the components of MetS, elevated blood pressure, elevated triglyceride and reduced HDL-cholesterol in men, and increased waist circumference, hyperglycemia, elevated triglyceride in women were risk factors for hyperuricemia. In subgroup analyses, the presence of concomitant MetS and general obesity posed strikingly higher risk for hyperuricemia among women (OR: 7.24, 95% CI: 4.56-11.50 in women, versus, OR: 2.90, 95% CI: 2.12-3.96 in men) when compared to individuals free of neither conditions (OR: 1.00, referent). In addition, the risk of hyperuricemia has increased up to 6-fold by the presence of MetS and general obesity among young adults aged less than 40 years old. Conclusion: Hyperuricemia was independently associated with MetS and general obesity, regardless of sex. These increases in risk of hyperuricemia were more prominent in women. Among women, those who had both MetS and general obesity were at nearly 7-fold increased risk for hyperuricemia compared to those without both conditions. It may be considered to incorporate hyperuricemia as one of the components of MetS. References Disclosure of Interests: None declared

Aim We designed this study to evaluate the prevalence of comorbidities, their monitoring states and association with treatment medication in Korean rheumatoid arthritis (RA) patients compared with patients from other countries. Methods We analyzed 1050 RA patients from 11 Korean centers and compared them with 3520 patients from 16 other countries using an international, cross-sectional study evaluating comorbidities of RA (COMORA) database. Results Annual evaluations of cardiovascular (CV) risk were less frequently performed in Korea (P = 0.0011). The prevalence of CV-associated morbidity was similar between Korean and international RA patients, although the proportions of current smokers, patients with a family history of CV disease, patients with hyperlipidemia, and patients with Framingham score > 20% were significantly lower in Korea (P < 0.0001 for all), and the antiplatelet agents were more optimally used in Korea (P = 0.0004). Prostate cancer screening was less frequently performed compared to other countries (P < 0.0001). Less than 10% of Korean RA patients were given influenza and pneumococcal vaccinations according to current recommendations. Conclusions There are differences in the prevalence of comorbidities and monitoring states of the risk factors between patients in Korea and in other countries. The prevalence of CV morbidity was similar between the two groups although the prevalence of CV risk factors was significantly low in Korea, suggesting that rheumatologists in Korea need to pay more attention to yearly CV risk monitoring, in addition to the screening of malignancy and vaccination of RA patients against infectious diseases.

Background/aims To evaluate the clinical course of hip arthritis and the risk factors for hip joint replacement in patients with ankylosing spondylitis (AS). Methods In this retrospective analysis, we evaluated 488 AS patients at a single tertiary hospital. At baseline and the most recent visit to the outpatient clinic from the patients with hip arthritis in AS, radiographic hip arthritis was evaluated using the Bath Ankylosing Spondylitis Radiology Hip Index (BASRI-h). Also the average of the hip joint space width (interbone distance) at three distinct sites between the acetabulum and femoral head was recorded. Results Among 488 patients with AS, 60 patients (12.3%) had hip arthritis. Erythrocyte sedimentation rate were associated with hip involvement (odds ratio, 1.01; 95% confidence interval [CI], 1.00 to 1.02; p = 0.004). Long disease duration and advanced axial disease were associated with severe hip arthritis (3 ≥ BASRI-h) at baseline. BASRI-h and interbone distance did not significantly change in patients with hip involvement during the follow-up period of 81.4 ± 35.7 months. Five patients had hip joint replacement surgery during follow-up period. The body mass index (BMI) and BASRI-h at baseline were associated with joint replacement surgery (hazard ratio [HR], 1.30; 95% CI, 1.00 to 1.67; p = 0.049 and HR, 20.64; 95% CI, 2.39 to 178.11; p = 0.006, respectively). Conclusions Most of the patients with hip arthritis in AS showed no significant radiographic progression during the follow-up period. High BMI and advanced hip arthritis at baseline were associated with hip joint replacement surgery in patients with AS.

This study aimed to evaluate the frequency and clinical characteristics of hydroxychloroquine (HCQ) retinopathy in Korean patients with rheumatologic diseases. We retrospectively reviewed medical records of 310 patients taking HCQ. Ophthalmic examinations included spectral-domain optical coherence tomography (SD-OCT), automated visual field test, and fundus autofluorescence. The severity of retinopathy was categorized as early, moderate, or severe, and the location was categorized as parafoveal, pericentral, or mixed pattern. Among 310 patients, 9 patients (2.9%) were diagnosed as HCQ retinopathy. Among the patients with HCQ use ≥ 5 years (n = 174), the frequency was 5.2%. Only 1 (11.1%) of the 9 patients was symptomatic. The mean daily dose per kilogram of real body weight of the 9 patients was 5.6 mg, and only 3 had used 6.5 mg or more. Four of the 9 patients had severe HCQ retinopathy. Six of the 9 patients showed pericentral or mixed pattern of retinal damage. Consequently, the frequency of HCQ retinopathy in Korean patients was not low, especially when administered at a high cumulative dose and for a long duration. Screening of HCQ retinopathy by the recommended guidelines that include SD-OCT seems useful and should be done to detect retinal damage earlier in patients with chronic exposure to HCQ., Graphical Abstract

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., Graphical Abstract

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.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 (10 mm ≤ discordance25 mm), positive discordance group II (≥25 mm), concordance (|10| mm), and negative discordance (≤ -10mm). Multinomial logistic regression analysis was performed to identify factors associated with discordance.Only 1350 (29.2%) patients were classified in the concordance group. Positive discordance was found in 52.3% of the patients (n = 2425), with 33.7% (n = 1563) showing marked discordance (≥25 mm). 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.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.

Background To evaluate the therapeutic benefits of the treat-to-target (T2T) strategy for Asian patients with early rheumatoid arthritis (RA) in Korea. Methods In a 1-year, multicenter, open-label strategy trial, 346 patients with early RA were recruited from 20 institutions across Korea and stratified into 2 groups, depending on whether they were recruited by rheumatologists who have adopted the T2T strategy (T2T group) or by rheumatologists who provided usual care (non-T2T group). Data regarding demographics, rheumatoid factor titer, anti-cyclic citrullinated peptide antibody titer, disease activity score of 28 joints (DAS28), and Korean Health Assessment Questionnaire (KHAQ) score were obtained at baseline and after 1 year of treatment. In the T2T group, the prescription for disease-modifying antirheumatic drugs was tailored to the predefined treatment target in each patient, namely remission (DAS28 < 2.6) or low disease activity (LDA) (2.6 ≤ DAS28 < 3.2). Results Data were available for 163 T2T patients and 162 non-T2T patients. At the end of the study period, clinical outcomes were better in the T2T group than in the non-T2T group (LDA or remission, 59.5% vs. 35.8%; P < 0.001; remission, 43.6% vs. 19.8%; P < 0.001). Compared with non-T2T, T2T was also associated with higher rate of good European League Against Rheumatism response (63.0% vs. 39.8%; P < 0.001), improved KHAQ scores (−0.38 vs. −0.13; P = 0.008), and higher frequency of follow-up visits (5.0 vs. 2.0 visits/year; P < 0.001). Conclusion In Asian patients with early RA, T2T improves disease activity and physical function. Setting a pre-defined treatment target in terms of DAS28 is recommended., Graphical Abstract

Aim To investigate the efficacy and safety of tacrolimus (TAC) versus leflunomide (LEF) when combined with methotrexate (MTX) in rheumatoid arthritis (RA) patients. Method This was a 24-week multi-center, double-blind, randomized, non-inferiority study targeting RA patients with moderate to severe Disease Activity Score of 28 joints (DAS28 > 3.2) who showed inadequate response to MTX. Patients were randomized into TAC or LEF (add-on to MTX) groups. Initial daily doses of TAC and LEF were 1.5 and 10 mg, respectively, for 4 weeks and then doubled until the end of the study. The primary endpoint was DAS28 comparison at 24 weeks. Results Eighty-seven patients were screened in 10 centers and 75 patients were randomized into two groups. Baseline demographics were comparable between TAC + MTX and LEF + MTX groups. The TAC + MTX group was non-inferior to the LEF + MTX group in terms of DAS28 at 24 weeks (mean difference of DAS28: -0.1812, 95% confidence interval: -0.8073, 0.4450). There was a greater number of adverse events in the LEF + MTX group (66 in LEF + MTX and 49 in TAC + MTX). Six patients presented with transaminitis in the LEF + MTX group compared with two patients in the TAC + MTX group. Conclusion The efficacy of TAC combined with MTX was non-inferior to LEF + MTX. It had a reasonable safety profile in RA patients with moderate to severe disease activity (http://cris.nih.go.kr; KCT0000781).

Objective In patients with rheumatoid arthritis (RA), morning stiffness is linked more to functional disability and pain than disease activity, as assessed by joint counts and markers of inflammation. As part of the Asia Pacific Morning Stiffness in Rheumatoid Arthritis Expert Panel, a group of eight rheumatologists met to formulate consensus points and develop recommendations for the assessment and management of morning stiffness in RA. Methods On the basis of a systematic literature review and expert opinion, a panel of Asian rheumatologists formulated recommendations for the assessment and medical treatment of RA. Results The panel agreed upon 10 consensus statements on morning stiffness, its assessment and treatment. Specifically, the panel recommended that morning stiffness, pain and impaired morning function should be routinely assessed in clinical practice. Although there are currently no validated tools for these parameters, they should be assessed as part of the patients' reported outcomes in RA. The panel also agreed on the benefits of low-dose glucocorticoids in RA, particularly for the improvement of morning stiffness. Conclusions These recommendations serve to guide rheumatologists and other stakeholders on the assessment and management of morning stiffness, and help implement the treat-to-target principle in the management of RA.

Because of frequent tuberculosis in patients with Takayasu arteritis (TA), a possible relationship between TA and tuberculosis has been proposed. However, there are no studies to date that have examined clinical manifestations in patients diagnosed with TA with or without tuberculosis. Two hundred sixty-seven patients were diagnosed with TA according to the 1990 American College of Rheumatology criteria between September 1994 and April 2014. Patients with TA were classified into groups with or without tuberculosis. Among the 267 patients with TA studied, 47 patients (17.7 %) who had a history of previous treatment of tuberculosis (34 patients), concurrent diagnosis of tuberculosis with TA (10 patients), or diagnosis of tuberculosis during the follow-up period for TA (3 patients) were included in the group with tuberculosis. The group with tuberculosis comprised of 33 patients (70.2 %) with pulmonary tuberculosis, 12 patients (25.5 %) with tuberculous lymphadenitis, and 2 patients (4.3 %) with tuberculosis of the skin and colon, respectively. Comorbid disease and patients' signs and symptoms were not significantly different between TA patients with and without tuberculosis. Additionally, the site of disease involvement in angiographic findings and distribution of angiographic type were similar between the two groups. In conclusion, tuberculosis including tuberculous lymphadenitis was frequently observed in patients with TA. Clinical features and angiographic findings in TA were not different according to the presence or absence of concomitant tuberculosis.

OBJECTIVES: This study aims to examine the effects of tocilizumab therapy on serum levels of interleukin (IL)-33 and IL-6 in rheumatoid arthritis (RA) patients. PATIENTS AND METHODS: Interleukin-33 and IL-6 levels in serum samples from 83 RA patients (10 males, 73 females; mean age 51.9 years; range, 26 to 77 years) and 12 healthy controls (2 males, 10 females; mean age 52.2 years; range, 39 to 62 years) were compared by cross-sectional, case control analysis. Of the RA patients, 40 received 24 weeks of tocilizumab therapy and were assigned to the prospective cohort. These 40 patients were then divided into two subgroups as responders and non-responders according to the American College of Rheumatology (ACR) 20. The remaining 43 RA patients did not receive tocilizumab therapy. Serum cytokine levels were analyzed at baseline and after 24 weeks of tocilizumab therapy in these patients. RESULTS: Interleukin-33 and IL-6 concentrations were significantly higher in RA patients than in healthy controls (p

Background Rheumatoid arthritis (RA) treatment may differ according to hepatitis B state and consequently may bring about different arthritis outcomes. However, whether hepatitis B affects treatment outcome remains unclear. We investigated differences in change in arthritis activity between RA patients according to concomitant hepatitis B virus infection. Methods A retrospective medical chart review was performed by two rheumatologic fellows using single center data, from January 2000 to March 2015. Among RA patients older than 18 years, patients with comorbidities that could affect RA treatment aside from hepatitis B were excluded. Using 1:3 propensity score matching, 40 hepatitis B virus surface antigen (HBsAg)-positive patients and 112 HBsAg-negative patients were included in the study. Data were collected longitudinally using standardized electronic forms. The longitudinal relationship between HBsAg-positivity and RA activity was analyzed using generalized estimating equations. Results RA activity showed time-dependent improvement. Reductions of swollen joint count over time were significantly larger in the HBsAg-negative group. However, changes in disease activity score in 28 joints with three variables (DAS28-3), tender joint count, erythrocyte sedimentation rate and C-reactive protein level did not differ between the groups. There were no differences in alanine aminotransferase level. HBsAg-positive patients were less likely to receive methotrexate (odds ratio [OR], 0.09; 95% confidence interval [CI], 0.04–0.19; P < 0.001) and more likely to receive sulfasalazine (OR, 3.67; 95% CI, 1.94–6.95; P < 0.001). Conclusion RA medication use varied according to HBsAg-positivity. However, improvement in RA activity was not significantly affected by concomitant hepatitis B infection., Graphical Abstract

BACKGROUND/AIMS To compare the clinical characteristics and outcomes of systemic lupus erythematosus between male and female Korean patients. METHODS A retrospective analysis was performed at a single tertiary hospital from August 1994 to May 2010. Male patients were matched with two to three female patients based on age and disease duration. Organ damage was assessed using the Systemic Lupus International Collaborating Clinics/American College of Rheumatology damage index (SLICC/ACR DI). RESULTS Fifty-three male patients were compared with 150 female patients. Renal disorders were found more frequently in male patients at disease onset (p < 0.001); the adjusted odds ratio (OR) demonstrated a significant sex preponderance for renal manifestations (OR, 3.26; 95% confidence interval [CI], 1.62 to 6.57). Diffuse proliferative lupus nephritis and end-stage renal disease requiring dialysis during the disease course were more prevalent in male patients (p = 0.025 and p < 0.001, respectively). The risk for requiring long-term dialysis was significantly higher in male than in female patients (OR, 4.02; 95% CI, 1.07 to 15.06), as was the mean SLICC/ACR DI (1.55 ± 1.35 vs. 1.02 ± 1.57, respectively; p = 0.028). CONCLUSIONS Our data demonstrate that Korean patients with lupus have characteristics similar to those of cohorts reported previously. Male patients had significantly higher incidences of renal manifestations and organ damage.

Aim Chronic periaortitis (CP) is a disease characterized by a fibro-inflammatory periaortic cuff and adventitia-predominant fibrosis. CP encompasses idiopathic retroperitoneal fibrosis and inflammatory abdominal aortic aneurysm (AAA), and recent studies have documented overlap between CP and immunoglobulin G4-related disease (IgG4-RD). This study aimed to investigate clinical characteristics and treatment outcomes of patients with CP. Method CP patients were identified by retrospective review of 1245 patients with International Classification of Diseases 10th edition code of aortitis or aortic disease. Patients were further classified into IgG4-related and non-IgG4-related CP according to the criteria proposed by a Japanese study. Results A total of 61 CP patients were identified. Patients showed a male predominance (70%) with median age of 61 at diagnosis. The abdominal aorta was most commonly involved (84%), while the thoracic aorta was affected in 46% of patients. Twenty-three (38%) patients had accompanying aortic aneurysm. Approximately 60% of patients achieved remission without further relapse during the course. Ten patients were classified as IgG4-related and 25 as non-IgG4-related. There was no significant difference in clinical features and outcomes between groups, with the exception of older age and greater pancreas involvement in IgG4-related patients. Conclusion We documented 61 CP patients including 10 IgG4-related cases. CP involved the abdominal aorta in most patients and the thoracic aorta in approximately 50% of patients. IgG4-related CP patients were older and had greater pancreas involvement, but disease outcomes appeared to be similar between IgG4-related and non-IgG4-related CP.

Background Ankylosing spondylitis (AS) is a male-predominant disease, and radiographic evidence of damage is also more severe in males. Estrogen modulates immune-related processes such as T cell differentiation and cytokine production. This study aimed to evaluate the effect of estrogen on the disease activity of spondyloarthritis (SpA). Methods The effects of estrogen on the development of arthritis were evaluated by performing ovariectomy and 17β-estradiol (E2) pellet implantation in zymosan-treated SKG mice. Clinical arthritis scores were measured, and 18F-fluorodeoxyglucose (18F-FDG) small-animal positron emission tomography/computed tomography performed to quantify joint inflammation. The expression of inflammatory cytokines in joint tissue was measured. Results 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 E2-treated mice than in sham-operated (sham) and ovariectomized mice. Expression of TNF, interferon-γ, and IL-17A was significantly reduced in E2-treated mice, whereas expression of sclerostin and Dickkopf-1 was increased in E2-treated mice compared with sham and ovariectomized mice. Conclusions Estrogen suppressed arthritis development in SKG mice, a model of SpA. Results of this study suggest that estrogen has an anti-inflammatory effect on the spondyloarthritis manifestations of the SKG arthritis model.

Aim To investigate the effects of Tubastatin A, a selective histone deacetylase-6 inhibitor, on synovial inflammation and joint destruction in a collagen antibody-induced arthritis (CAIA) mouse model. Methods Collagen antibody-induced arthritis mice were given daily intraperitoneal injections of various concentrations of Tubastatin A (0, 10, 50, 100 mg/kg). The clinical score and paw thickness were measured. Mice were sacrificed on day 15, and the expression of tumor necrosis factor (TNF)-α, interleukin (IL)-1 and IL-6 in the serum were analyzed using enyme-linked immunosorbent assay (ELISA). Two pathologists independently measured the synovitis score. Micro-computed tomography (CT) scans of the joints were performed to quantify joint destruction. The expression of IL-6 from human fibroblast-like synoviocytes (FLSs) after incubation with various doses of Tubastatin A (0, 0.75, 1.5, 3 μmol/L) was measured using ELISA. Results The clinical arthritis score was significantly attenuated and paw thickness was lower in the group treated with 100 mg/kg Tubastatin A compared with those treated with vehicle alone. The synovitis score was significantly reduced in the 100 mg/kg Tubastatin A-treated group compared with the control group. Micro-CT showed that quantitative measures of joint destruction were significantly attenuated in the 100 mg/kg Tubastatin A-treated group compared with the control. The expression of IL-6 in the sera was lower in the mice treated with Tubastatin A compared with the control. The expression of IL-6 in human FLSs decreased dose-dependently after incubation with Tubastatin A without affecting cell viability. Conclusions Tubastatin A successfully ameliorated synovial inflammation and protected against joint destruction in CAIA mice, at least in part, by modulating IL-6 expression.

Although chronic kidney disease (CKD) may constitute a chronic inflammatory state indicated by elevated inflammatory mediators such as tumor necrosis factor alpha (TNF-α), the impact of anti-TNF-α therapy on progression of CKD in patients with rheumatoid arthritis (RA) is unclear. Seventy patients with RA and CKD were retrospectively analyzed. Outcomes were evaluated using the difference in the annual change of estimated glomerular filtration rate (eGFR) between patients treated with anti-TNF-α or without. Anti-TNF-α therapy significantly decreased disease activity score (DAS) 28 from 5.32 ± 0.78 to 3.59 ± 0.85 (p < 0.001). There was a tendency toward stabilization of eGFR after a mean of 2.9 ± 1.1 years from 50.3 ± 8.4 ml/min/1.73 m(2) to 54.5 ± 16.0 ml/min/1.73 m(2) in patients received anti-TNF-α therapy along with decreased DAS28 (p = 0.084). Conversely, eGFR decreased significantly in patients not receiving anti-TNF-α therapy after a mean of 2.8 ± 1.7 years from 52.6 ± 7.5 ml/min/1.73 m(2) to 46.5 ± 11.5 ml/min/1.73 m(2) (p = 0.041) without significant DAS28 change (p = 0.078). The annual change of eGFR was significantly different between patients treated with anti-TNF-α drugs and without (2.0 ± 7.0 ml/min/1.73 m(2)/year vs. -1.9 ± 4.0 ml/min/1.73 m(2)/year; difference in mean vs. -3.9 ± 7.3 ml/min/1.73 m(2)/year; p = 0.006). Use of anti-TNF-α drugs was significantly associated with positive annual change of eGFR in multivariate logistic regression analysis (p = 0.019). Among patients with RA and CKD, treatment with anti-TNF-α drugs was associated with less renal function decline. Anti-TNF-α drugs may be beneficial for managing RA combined with CKD.

Aim To evaluate the clinical characteristics and outcomes of nonradiographic axial spondyloarthritis (nr-axSpA) in Korean patients. Methods A retrospective analysis evaluated 155 patients with nr-axSpA at a single tertiary hospital between January 2001 and January 2011. Baseline characteristics and clinical courses were reviewed and compared with those of patients with ankylosing spondylitis (AS). Results The mean age at disease onset was 29.5 ± 10.8 years and 52 (33.5%) patients were female. The mean age at symptom onset was older (29.5 ± 10.8 vs 25.9 ± 9.2, respectively, P

Objectives Although many diagnostic criteria of Behcet's disease (BD) have been developed and revised by experts, diagnosing BD is still complicated and challenging. No metabolomic studies on serum have been attempted to improve the diagnosis and to identify potential biomarkers of BD. 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 (HCs) were performed via gas chromatography with time-of-flight mass spectrometry (GC/TOF-MS) with multivariate statistical analyses. Results A total of 104 metabolites were identified from samples. The serum metabolite profiles obtained from GC/TOF-MS analysis can distinguish BD patients from HC group in discovery set. The variation values of the partial least squared-discrimination analysis (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 model. A panel of five metabolic biomarkers, namely, decanoic acid, fructose, tagatose, linoleic acid and oleic acid were selected and adequately validated as putative biomarkers of BD (sensitivity 100%, specificity 97.1%, area under the curve 0.998) in the discovery set and independent set. The PLS_DA model showed clear discrimination of BD and HC groups by the five metabolic biomarkers in independent set. Conclusions This is the first report on characteristic metabolic profiles and potential metabolite biomarkers in serum for reliable diagnosis of BD using GC/TOF-MS.

Objectives This study examined and compared the persistence of adalimumab, etanercept, infliximab, or abatacept as first- and subsequent-line treatment for rheumatoid arthritis in the South Korean clinical practice. Methods We conducted a retrospective cohort study with patients receiving adalimumab, etanercept, infliximab, or abatacept between July 1, 2009 and December 31, 2012, using the nationwide Korean National Health Insurance database. Patients who were receiving a newly initiated biologic treatment and those who switched from other biologic treatment were identified and classified into first- and subsequent-use cohorts, respectively. Treatment patterns during the 1-year after treatment initiation were measured as persistence, and discontinuation including restarting, switching, and stopping. The Cox proportional hazard model was used to estimate hazard ratios (HRs) and their 95% confidence intervals (CIs) for discontinuation of biologic treatments. Results We identified 4114 patients for the first-use cohort and 992 patients for the subsequent-use cohort. Treatment persistence with adalimumab, etanercept, and infliximab was observed in 52.5%, 56.1%, and 52.6% of the patients, respectively, in the first-use cohort, without significant differences in duration of persistence among the treatments according to the Cox proportional hazard model. In the subsequent-use cohort, treatment persistence with adalimumab, etanercept, infliximab, and abatacept was observed in 45.7%, 58.5%, 43.0%, and 60.4% of the patients, respectively. The Cox proportional hazard model found that the patients who were receiving etanercept (HR = 0.68, 95% CI: 0.52–0.88) and abatacept (HR = 0.53; 95% CI: 0.37–0.74) were significantly less likely to discontinue the treatment than those who were receiving infliximab. Conclusions Adalimumab, etanercept, and infliximab had similar levels of persistence during the 1-year after treatment initiation, when used as first-line treatment. However, when used as a subsequent-line treatment, etanercept and abatacept had higher persistence than infliximab or adalimumab. Persistence could be a consideration when selecting the subsequent-line biologic treatment for patients with rheumatoid arthritis in South Korea.

This study aimed to evaluate the prevalence of comorbidities in patients with rheumatoid arthritis (RA) compared with the non-RA population. The 2010-2012 Korea National Health and Nutrition Examination Survey (KNHANES), which assesses the general health status of populations in South Korea using interviews and basic health assessment, was analyzed retrospectively. Weighted prevalence and odds ratio (OR) of comorbidities were analyzed in patients with RA compared with the non-RA population. The overall weighted (n = 37,453,158) prevalence of RA was 1.5%. Patients with RA were older and more female predominant than subjects without RA. The prevalence of living in an urban area, college graduation, alcohol consumption and smoking was lower in patients with RA than non-RA. Patients with RA had more comorbidities including hypertension, dyslipidemia, myocardial infarction (MI) or angina, stoke, osteoarthritis, lung cancer, colon cancer, pulmonary tuberculosis, asthma, diabetes, depression, thyroid disease and chronic kidney disease. After adjusting socioeconomic and lifestyle characteristics, RA was associated with an increased prevalence of MI or angina (OR 1.86, 95% CI 1.17-2.96, p = 0.009), pulmonary TB (OR 1.95, 95% CI 1.24-3.09, p = 0.004), asthma (OR 1.97, 95% CI 1.05-3.71, p = 0.036), thyroid disease (OR 1.71, 95% CI 1.05-2.77), depression (OR 2.38, 95% CI 1.47-3.85, p < 0.001) and hepatitis B (OR 2.34, 95% CI 1.15-4.80, p = 0.020) compared with the non-RA population. Prevalence of solid cancer was not significantly associated with RA after adjustment.

Objectives This study aimed to evaluate the association of knee osteoarthritis (OA) with comorbidities and health-related quality of life (HRQOL). Methods A total of 8,907 (weighted n = 13,687,058) participants aged ≥50 years who had undergone knee radiography were selected from the 2010–2012 Korea National Health and Nutrition Examination Survey. OA was classified into four subgroups based on the presence or absence of pain and radiographic OA (ROA): non-OA (Pain-/ROA-), pain only (Pain+/ROA-), ROA only (Pain-/ROA+), and painful ROA (Pain+/ROA+). ROA was defined as Kellgren–Lawrence grade ≥ 2. HRQOL measurements including EuroQOL visual analogue scale (EQ-VAS) scores and the five dimensions and summary index of the EuroQOL-5 dimension (EQ-5D index) were also analyzed. Multivariable logistic regression and linear regression analyses were performed. Results After adjustment for socioeconomic and lifestyle characteristics, cardiovascular disease, malignancy, and other comorbidities were not significantly associated with OA. Pain only and painful ROA were each significantly associated with limitations in physical activity (odds ratio (OR) 2.66, 95% CI 2.07–3.44, p < 0.001 and OR 2.83, 95% CI 2.25–3.58, p < 0.001, respectively), lower EQ-VAS (β-coefficient = -10.95, p < 0.001 and β-coefficient = -9.75, p < 0.001, respectively), and EQ-5D index (β-coefficient = -0.10, p < 0.001 and β-coefficient = -0.13, p < 0.001) compared with the non-OA group, whereas ROA only was not associated with limitations in physical activity or lower HRQOL score. Conclusions Comorbidities were not significantly associated with knee OA after adjustment. Knee OA was associated with physical activity and HRQOL. Painful knee OA, with or without ROA, was more strongly associated with decreased physical activity and lower quality of life than ROA without pain.

To 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.We 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.A 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%, p 0.01) and matched cohorts (19.7 vs. 15.0%, p 0.01). In per protocol analysis, TNFI starters had much higher remission rates in unmatched (37.2 vs. 28.0%, p = 0.04) and matched cohorts (35.4 vs. 19.1%, p = 0.04). However, in matched cohorts, no significant differences were observed between two groups in HAQ-DI and EQ-5D scores.We 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.

Introduction: Synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome is an increasingly recognized entity. The hip joint is known as a less frequently affected site in SAPHO syndrome, and there has been limited reports about hip joint diseases caused by SAPHO syndrome, and as such adequate treatment for this disease spectrum is still not fully elucidated. Case: We describe the case of a 52-year-old man admitted for SAPHO syndrome who went on to be diagnosed with advanced secondary hip arthritis associated with disabling right hip pain. The diagnosis of SAPHO syndrome was delayed; the patient was given a clinical diagnosis of osteomyelitis and treated with prolonged courses of antibiotics and open surgical debridement at previous tertiary health facility. The patient underwent 2-stage joint replacement surgery in our hospital. At 1 year after the surgery, he is well, with minimal right hip pain and the prosthesis is functioning well. Conclusion: This case shows the safety and effectiveness of the 2-stage joint replacement in treating destructive hip disease caused by SAPHO syndrome mimicking infectious arthritis.

To identify the clinical features of elderly-onset rheumatoid arthritis (EORA) and their impact on disease outcome.A 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).EORA 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 duration10 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 of5 years, OR 3.07, CI 1.64-5.74: disease duration of 5 to 10 years).Disease onset in older age was associated independently with functional disability of RA patients who have relatively short disease duration.

The aim of this study is to compare the expression of TIM-3 from CD4+ T cells from rheumatoid arthritis (RA) patients and healthy controls and to evaluate the effect of galectin-9 (Gal-9) on apoptosis of CD4+ T cells in these patients. CD4+ T cells from RA patients and healthy controls were isolated from peripheral blood mononuclear cells and were activated. The expression of TIM-3 mRNA in CD4+ T cells was measured using real-time polymerase chain reaction. CD4+ T cells were activated in the presence of graded doses of Gal-9 or control, and Gal-9-induced cytotoxicity and apoptotic activity of CD4+ T cells were analyzed using MTT assays and annexin-V staining, respectively. TIM-3 mRNA expression was significantly lower in CD4+ T cells from RA patients compared with those in healthy controls (p = 0.028). CD4+ T cell survival as measured by MTT assay when incubated with Gal-9 (15 nM) was significantly higher in RA patients than in healthy controls (p = 0.002). Apoptotic activity of CD4+ T cells from healthy controls as measured by annexin staining increased with graded doses of Gal-9 (0 nM vs. 30 nM, 0 nM vs. 90 nM, p = 0.016 each). However, apoptotic activity of CD4+ T cells from RA patients did not change despite the stimulation with Gal-9. Gal-9-mediated apoptosis of CD4+ T cells is dysfunctional in RA patients. Blunted Gal-9-mediated apoptosis may be exerted through underexpression of TIM-3 that negatively regulates Th1 response. Our data suggest that TIM-3 and its interaction with Gal-9 may play an important role in the pathogenesis of RA and may represent a potential therapeutic target.

Cancerous inhibitor of protein phosphatase 2A (CIP2A) is a recently identified oncoprotein that leads to cellular proliferation in cancer cells. We aim to investigate CIP2A expression in fibroblast-like synoviocytes (FLS) and its association with the histopathological grade of synovitis and the invasive function of FLS in rheumatoid arthritis (RA). CIP2A protein expression was measured in 8 RA FLS and 8 OA FLS using Western blot analysis. CIP2A mRNA expression from 19 RA FLS and 7 OA FLS was measured using real-time PCR. Synovitis score of RA FLS-matched synovial tissues was semiquantitatively measured by two independent pathologists. An in vitro cell invasion assay was performed using RA FLS treated with CIP2A small interfering RNA (siRNA) or with control vector. Western blot analysis showed that CIP2A is more frequently overexpressed in RA FLS compared with OA FLS. CIP2A mRNA expression was higher in RA FLS compared with those in OA FLS, but did not reach statistical significance (P = 0.076). In RA, total synovitis score was strongly correlated with FLS CIP2A mRNA expression (rs = 0.849, P = 0.043). TNF-α treatment induced a robust increase in the invasive function of control FLS (P = 0.0021), but no significant effect was observed in CIP2A siRNA-treated FLS. Our data demonstrate that CIP2A expression is closely associated with the histopathological score of synovitis and invasive function of FLS in RA. These results suggest that CIP2A may play a critical role in the destructive process in RA and warrant further investigation of CIP2A as a therapeutic target.

T-cell immunoglobulin- and mucin-domain-containing molecule 3 (TIM-3) is a novel transmembrane protein that is involved in the regulation of T-helper 1 (Th1)-cell-mediated immunity. This study was undertaken to investigate the expressions of TIM-3 and its ligand galectin 9 (Gal-9) with respect to disease activity in rheumatoid arthritis (RA).Blood was collected from 39 RA patients and 31 healthy controls. Blood leucocyte TIM-3 and Gal-9 mRNA levels and RA disease activity were determined. Synovial tissue (ST) from five RA patients and five osteoarthritis (OA) patients were examined for TIM-3 mRNA expression and were also analysed for TIM-3 by immunohistology.TIM-3 mRNA expression was significantly higher in the ST of RA patients than in the ST of OA patients. TIM-3 was expressed in the synovial sublining area in ST of RA patients but not in OA ST. TIM-3 mRNA expression from peripheral blood mononuclear cells (PBMCs) of RA patients was negatively correlated with the 28-joint Disease Activity Score (DAS28). Gal-9 mRNA level in PBMCs of RA patients was higher than in healthy controls, and was significantly higher in patients with low disease activity compared to those with moderate to high disease activity. Gal-9 mRNA expression in PBMCs of RA patients was positively correlated with forkhead box P3 (FoxP3) mRNA expression.TIM-3 and its interaction with Gal-9 are closely associated with RA disease activity and may play an important role in the pathogenesis of RA. In addition to the negative regulatory effect of Gal-9 mediated through the TIM-3-Gal-9 pathway, Gal-9 may exert its suppressive effect on RA disease activity by modulation of regulatory T (Treg) cells.

The outcome of systemic lupus erythematosus (SLE) is largely influenced by the existence of lupus nephritis (LN), and its histologic classification guides the treatment and prognosis of SLE. International Society of Nephrology-Renal Pathology Society (ISN-RPS) announced a revised classification of LN in 2004. The present study investigated the differential outcome of World Health Organization (WHO) class III LN when reclassified according to ISN-RPS classification. Forty-three patients with biopsy-proven WHO class III LN at a single tertiary hospital were included in the study. Baseline characteristics at the time of renal biopsy and clinical data during follow-up were obtained from medical records. Renal response to treatment at one-year follow-up was analyzed in three ways; complete response (CR), partial response (PR), and no response (NR). Of 43 patients with previous WHO class III LN, 12 cases were reclassified into ISN-RPS class IV (9 cases of class IV-S and 3 cases of IV-G). Baseline characteristics at the time of renal biopsy were not different between the reclassified class IV and remaining class III LN group except activity index on renal histology, which was significantly elevated in the reclassified class IV group (4.90 vs. 6.75; P = 0.02). Significantly higher number of patients with remaining class III LN achieved CR to treatment than those with reclassified class IV LN at one-year follow-up since initial biopsy (CR: PR: NR; 16:7:7 vs. 3:1:8; P = 0.032). Our study suggests that the ISN-RPS classification is more advantageous in predicting renal outcome and guiding treatment when evaluating previously classified WHO class III LN.

Objective. This cross-sectional study aimed to investigate the association between rheumatoid factor (RF) positivity and bone mineral density (BMD) in male Korean subjects without any history of joint disease. Methods. Of 84,344 males who had undergone a comprehensive health checkup program in 2012, 1,390 male health examinees were recruited, whose BMD and RF results were available. A RF titer ≥20 IU/mL was considered positive. BMD was measured at lumbar spine (L1∼L4) or hip (femoral neck and total hip) by dual-energy X-ray absorptiometry. Results. The association between RF positivity and BMD was assessed by multiple linear regression analysis. The mean age was 52.7±10.9 years (range 19∼88 years), and RF was detected in 64 subjects (4.6%). Demographics and laboratory data were not different between RF-positive and -negative subjects except hepatitis B surface antigen (HBsAg), which was more frequently seen in RF-positive subjects (15.6% vs. 4.3%, p=0.001). RF-positive subjects had significantly lower BMD compared to RF-negative subjects in lumbar spine but not in total hip regardless of the existence of HBsAg (1.17±0.16 g/㎠ vs. 1.10±0.18 g/㎠, p=0.002 in total subjects; 1.17±0.16 g/㎠ vs. 1.10±0.18 g/㎠, p=0.004 in HBsAg-negative subjects). After adjusting for multiple confounders, RF positivity was negatively associated with lumbar spine BMD (B=-0.088 and standard error=0.035, p=0.011). Conclusion. Our results show that the presence of RF could have an unfavorable impact on bone density in apparently normal males. Additional studies to elucidate the osteoimmunological mechanism of rheumatoid factor are warranted. (J Rheum Dis 2019;26:31-40)

Wegener's granulomatosis (WG), Churg-Strauss syndrome, and microscopic polyangiitis (MPA) are closely related small vessel vasculitides characterized by anti-neutrophil cytoplasmic antibodies (ANCA). Although there were some reports of MPA presenting with claudication, there are very few reports on WG presenting with claudication of calf muscles. We report an unusual case of ANCA-associated vasculitis in a 75-year-old man who presented with bilateral calf claudication. Comprehensive evaluations, including electromyography, nerve conduction study, lower extremity magnetic resonance imaging, and Doppler scan, did not reveal any other cause of bilateral calf claudication. P-ANCA and anti-myeloperoxidase antibody was positive, but the anti-proteinase 3 antibody was negative. Chest computed tomography scan showed subpleural honeycombing and reticulation, predominantly in both basal lung areas. Biopsy of the calf muscle showed granulomatous vasculitis. Kidney biopsy was also performed which revealed focal necrotizing glomerulonephritis. Our patient does not exhibit typical clinical features for WG, but histopathologic findings of necrotizing granulomatous vasculitis in calf muscle biopsy is highly suggestive of WG.