Metabolic discrimination of synovial fluid between rheumatoid arthritis and osteoarthritis using gas chromatography/time-of-flight mass spectrometry.

INTRODUCTION: Rheumatoid arthritis (RA) and osteoarthritis (OA) are clinicopathologically different. OBJECTIVES: We aimed to assess the feasibility of metabolomics in differentiating the metabolite profiles of synovial fluid between RA and OA using gas chromatography/time-of-flight mass spectrometry. METHODS: We first compared the global metabolomic changes in the synovial fluid of 19 patients with RA and OA. Partial least squares-discriminant, hierarchical clustering, and univariate analyses were performed to distinguish metabolites of RA and OA. These findings were then validated using synovial fluid samples from another set of 15 patients with RA and OA. RESULTS: We identified 121 metabolites in the synovial fluid of the first 19 samples. The score plot of PLS-DA showed a clear separation between RA and OA. Twenty-eight crucial metabolites, including hypoxanthine, xanthine, adenosine, citrulline, histidine, and tryptophan, were identified to be capable of distinguishing RA metabolism from that of OA; these were found to be associated with purine and amino acid metabolism. CONCLUSION: Our results demonstrated that metabolite profiling of synovial fluid could clearly discriminate between RA and OA, suggesting that metabolomics may be a feasible tool to assist in the diagnosis and advance the comprehension of pathological processes for diseases.

Factors associated with radiographic progression in patients with Takayasu's arteritis.

OBJECTIVES: To identify the factors related to radiographic progression in patients with Takayasu's arteritis (TAK). METHODS: A retrospective cohort study was conducted among patients with TAK who underwent computed tomography angiography (CTA) at least twice in a 2-5-year interval. Radiographic progression was defined as newly developed and/or aggravated (more than 20%) characteristic CTA findings. Correlation analysis was performed using a multivariate Cox regression model. RESULTS: The cohort included 153 TAK patients with a mean CTA interval of 3.53 years, and 24 (15.7%) showed radiographic progression. Those with progression showed higher acute-phase reactant levels (erythrocyte sedimentation rate [ESR], 26.06 vs. 35.72 mm/h, p=0.040; C-reactive protein [CRP], 0.45 vs. 1.13 mg/dL, p<0.001), were younger at the initial CTA (43.70 vs. 31.81 years, p<0.001), and were more likely to be receiving immunosuppressants (14 [10.9%] vs. 7 [29.2%] patients, p=0.038). Multivariate Cox regression analysis revealed age at the initial CTA (hazard ratio [HR]=0.945, confidence interval [CI]=0.898-0.995, p=0.030) and area under the curve (AUC) of CRP levels (HR=2.126, CI=1.046-4.319, p=0.037) as significant factors for radiographic progression. In a subgroup of patients with high CRP levels, 30.4% (14/24) showed progression; only age at the initial CTA was significantly different (37.03 vs. 27.10 years, p=0.012) between those with and without progression. CONCLUSIONS: Higher CRP levels and younger age were risk factors of radiographic progression in patients with TAK. In the high CRP group, younger patients are more prone to progression and may need aggressive anti-inflammatory treatment.

Patient Perspectives and Preferences Regarding Gout and Gout Management: Impact on Adherence.

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.

Variation in the synovial fluid metabolome according to disease activity of rheumatoid arthritis.

OBJECTIVES: Because genetic and environmental factors both contribute to rheumatoid arthritis (RA), metabolomics could be a very useful tool to elucidate the pathophysiology of RA, and to predict response to treatment. This study was carried out to investigate synovial fluid (SF) metabolic perturbation in RA patients according to the degree of disease activity using gas chromatography/time-of-flight mass spectrometry (GC/TOF MS). METHODS: SF samples were obtained from 48 RA patients. Disease activity was assessed using DAS28-ESR(3). SF metabolomics profiling was performed using GC/TOF-MS, in conjunction with multivariate statistical analyses and pathway analyses. RESULTS: Significant discrimination of metabolite profiles between moderate and high disease activity groups was shown by PLS-DA, which provided evidence that SF metabolic profiles predicted disease activity. We found the significant correlation between DAS28-ESR(3) value and the intensities of 12 metabolites. The intensities of glycocyamine and indol-3-lactate positively correlated with DAS28-ESR(3) value. On the other hand, ß-alanine, asparagine, citrate, cyano-L-alanine, leucine, nicotinamide, citrulline, methionine, oxoproline, and salicylaldehyde negatively correlated with DAS28-ESR(3) value. We found fifteen pathways that were significantly associated with disease activity in RA and that the higher the disease activity, the more amino acid metabolic processes were affected. CONCLUSIONS: We found the SF metabolic alterations in RA patients according to disease activity by using GC/TOF MS and identified 12 candidate metabolic biomarkers that may well reflect the disease activity of RA. SF metabolomic approaches based on GC/TOF MS might provide additional information relating to monitoring disease activity in RA.

Increased Overall Heart Rate Irregularity Risk by Hyperuricemia in the General Population: Results from the Korean National Health and Nutrition Examination Survey.

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 1.71-5.18). 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.

Disease Characteristics and Change in Arthritis Activity according to Treatment in Hepatitis B Surface Antigen-positive Rheumatoid Arthritis Patients: a Retrospective Chart Review Study.

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.

Treat-to-Target Strategy for Asian Patients with Early Rheumatoid Arthritis: Result of a Multicenter Trial in Korea.

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.

Positive selection of type II collagen-reactive CD80high marginal zone B cells in DBA/1 mice.

To investigate whether dysregulated selection of autoreactive marginal zone (MZ) B cells is involved in autoimmune diseases, we examined MZ B cell profile in multiple strains of mice, and found that type II collagen (CII)-reactive autoreactive CD80high MZ B cells spontaneously developed in the DBA/1, but not in C57BL/6 mice. CD80high MZ B cells that were characteristically found in DBA/1 mice expressed higher levels of TACI, SLAM3, and SLAM6 than the usual CD80low MZ B cells. Notably, the CD80high MZ B cells were more sensitive to ibrutinib, a Bruton's tyrosine kinase inhibitor, than CD80low MZ or follicular B cells and their transient depletion via intravenous injection of ibrutinib significantly delayed the induction of collagen-induced arthritis (CIA). In summary, we suggest that the positive selection of CII-reactive CD80high MZ B cells is a critical homeostatic process predisposing the DBA/1 mice to the CIA induction.

Early Development in the Peritoneal Cavity of CD49dhigh Th1 Memory Phenotype CD4+ T Cells with Enhanced B Cell Helper Activity.

The Th cells that regulate peritoneal B-1 cell functions have not yet been well characterized. To address this question, we investigated peritoneal CD4(+) T cells, observed a high frequency of the conjugates of B-CD4(+) T cells in the peritoneal cavity, and identified a population of CD49d(high)CD4(+) T cells that constituted about half of all CD4(+) T cells in the peritoneal cavity, but were rarely found in other compartments. Peritoneal CD49d(high)CD4(+) T cells were CD44(high)CD62L(low); expressed integrin α4ß1 and CXCR3; and rapidly secreted IFN-γ, TNF-α, and IL-2, showing features of proinflammatory Th1 cells. Peritoneal CD49d(high)CD4(+) T cells developed spontaneously, were detected at the age of 12 d, and showed stem cell-like properties. Their development was observed in mice deficient for signaling lymphocytic activation molecule-associated protein, but not in athymic nude mice and mice lacking in expression of MHC class II on thymic epithelial cells. Peritoneal CD49d(high)CD4(+) T cells were more resistant to irradiation and more sensitive to NAD-induced cell death than CD49d(low)CD4(+) T cells. Notably, peritoneal CD49d(high)CD4(+) T cells also showed some characteristics of follicular Th cells, such as the expression of programmed cell death 1, ICOS, IL-21, and CXCR5. Moreover, peritoneal CD49d(high)CD4(+) T cells enhanced the secretion of IgM Abs by B-1a cells and IgG Abs by splenic B cells. These data suggest that peritoneal CD49d(high)CD4(+) T cells may be innate-like CD4(+) T cells, which develop early and have a dual capacity to support both humoral and cellular immunity.

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

OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Frequency and Clinical Characteristics of Hydroxychloroquine Retinopathy in Korean Patients with Rheumatologic Diseases.

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.

Urinary Metabolomic Profiling to Identify Potential Biomarkers for the Diagnosis of Behcet's Disease by Gas Chromatography/Time-of-Flight-Mass Spectrometry.

Diagnosing Behcet's disease (BD) is challenging because of the lack of a diagnostic biomarker. The purposes of this study were to investigate distinctive metabolic changes in urine samples of BD patients and to identify urinary metabolic biomarkers for diagnosis of BD using gas chromatography/time-of-flight-mass spectrometry (GC/TOF-MS). Metabolomic profiling of urine samples from 44 BD patients and 41 healthy controls (HC) were assessed using GC/TOF-MS, in conjunction with multivariate statistical analysis. A total of 110 urinary metabolites were identified. The urine metabolite profiles obtained from GC/TOF-MS analysis could distinguish BD patients from the HC group in the discovery set. The parameter values of the orthogonal partial least squared-discrimination analysis (OPLS-DA) model were R²X of 0.231, R²Y of 0.804, and Q² of 0.598. A biomarker panel composed of guanine, pyrrole-2-carboxylate, 3-hydroxypyridine, mannose, l-citrulline, galactonate, isothreonate, sedoheptuloses, hypoxanthine, and gluconic acid lactone were selected and adequately validated as putative biomarkers of BD (sensitivity 96.7%, specificity 93.3%, area under the curve 0.974). OPLS-DA showed clear discrimination of BD and HC groups by a biomarker panel of ten metabolites in the independent set (accuracy 88%). We demonstrated characteristic urinary metabolic profiles and potential urinary metabolite biomarkers that have clinical value in the diagnosis of BD using GC/TOF-MS.

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

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 (10 mm ≤ discordance <25 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. RESULTS: 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. 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.

Clinical significance of bone marrow hemophagocytosis in adult patients with malignancy and non-malignancy-induced hemophagocytic lymphohistiocytosis.

Bone marrow hemophagocytosis is a frequently observed but not mandatory finding for the diagnosis of hemophagocytic lymphohistiocytosis (HLH). However, the impact of bone marrow hemophagocytosis on the diagnosis of HLH is still not clear in adult patients. Thus, we retrospectively analyzed adult patients with bone marrow hemophagocytosis between 2000 and 2014 to determine its clinical significance. Among 264 patients with bone marrow hemophagocytosis, malignant disorders were the predominant underlying cause (n = 170, 64 %), especially T/NK-cell (n = 88) and B-cell (n = 45) lymphomas compared to infectious disease (48/264, 18 %). The data for HLH-2004 diagnostic criteria was available in 182 patients, and only 29 % (77/264) of patients with ≥ five positive criteria could be diagnosed with HLH. Among the criteria for the diagnosis of HLH, increased serum ferritin (89 %) was more common than hypofibrinogenemia, hypertriglyceridemia, and bicytopenia (<40 %). The median overall survival was worse in patients with malignancy (9.0 months, 95 % confidence interval [CI] 5.6-12.5) than in those with non-malignant disorders (71.8 months, 95 % CI 56.5-87.1, P < 0.001). In patients with malignancy, the overall survival of patients fulfilling the HLH-2004 criteria was significantly worse than patients who did not (P < 0.001). In conclusion, our results suggest that bone marrow hemophagocytosis might be an important finding in the diagnosis of HLH in adult patients. Considering the high incidence of malignancy as a predisposing disorder for HLH, immediate evaluation should be performed in adult patients with bone marrow hemophagocytosis.

Efficacy of tocilizumab therapy in Korean patients with adult-onset Still's disease: a multicentre retrospective study of 22 cases.

OBJECTIVES: To evaluate the efficacy of tocilizumab (TCZ), a monoclonal antibody against the interleukin (IL)-6 receptor, for refractory adult-onset Still's disease (AOSD) in the Korean population. METHODS: This retrospective study included 22 Korean patients with refractory AOSD who were given TCZ at one of seven university hospital-based clinics for rheumatic disease. Patients were subdivided into groups according to disease course: monocyclic, systemic polycyclic, and chronic articular. Modified Pouchot scores, including laboratory and clinical findings, were analysed at 6 months and 12 months. RESULTS: TCZ was given at 4-8 mg/kg every 4-5 weeks (8 mg/kg every 4-5 weeks in 18 patients, 6 mg/kg every 4 weeks in 2, and 4 mg/kg every 4 weeks in 2) for 7.5 months (median, IQR: 4.0-12.3). A good response (measured as a decrease of >2 in the modified Pouchot score) was achieved in 50.0% of patients (11 of 22) at 6 months and in 64.3% (9 of 14) at 12 months. The dose of corticosteroid dose was reduced from 11.5 mg/day (median, IQR: 10.0-21.3) immediately before TCZ therapy to 7.5 mg/day (median, IQR: 5.0-10.0, p=0.002) at 6 months and finally to 6.3 mg/day (median, IQR: 5.0-7.5, p=0.002) at 12 months. Only one patient discontinued TCZ treatment due to facial swelling accompanied by high blood pressure. In all others, adverse events subsided with delayed TCZ therapy, and TCZ therapy was continued successfully without problems. CONCLUSIONS: TCZ was effective for treating Korean AOSD patients who were refractory to conventional therapy or other anti-cytokine biologics, showing a corticosteroid-sparing effect and an acceptable tolerance profile.

Comparison of clinical characteristics in patients with Takayasu arteritis with and without concomitant tuberculosis.

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.

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.

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 (80 % of the data) and a validation set (20 % 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 R (2) 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-5D = 0.95-0.21 × HAQ-DI-0.24 × pain VAS/100-0.01 × DAS28 (adjusted R (2) = 57.6 %, RMSE = 0.1654 and MAE = 0.1222). 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.

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.

Effect of anti-tumor necrosis factor alpha treatment of rheumatoid arthritis and chronic kidney disease.

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.

Sex-specific disparities in disease activity scores among patients with axial spondyloarthritis and their implications for evaluating the response to tumor necrosis factor alpha inhibitor therapy.

BACKGROUND: We aimed to investigate whether there are sex differences in disease activity measures among patients with axial spondyloarthritis (axSpA) and to determine any potential impact on the assessment of treatment responses to tumor necrosis factor alpha inhibitors (TNFi). METHODS: Using the Korean College of Rheumatology Biologics and Targeted Therapy (KOBIO) registry data, we compared sex differences in changes in the Bath Ankylosing Spondylitis Disease Activity Score (BASDAI) and Ankylosing Spondylitis Disease Activity Score (ASDAS) levels at baseline and one year after TNFi initiation in patients with axSpA. RESULTS: This study included 1,753 patients with axSpA who started or changed TNFi, of whom 1,343 (76.6%) were male. At baseline, the mean BASDAI and ASDAS scores of all patients were 5.98 and 3.6, respectively. The BASDAI changes between baseline and the one-year follow-up were independently associated with sex (𝛽 = 0.343, p = 0.011), whereas ASDAS was not (𝛽 = 0.079, p = 0.235). When judging the effect of TNFi at one-year of treatment, male patients were more likely to be assessed as effective by the BASDAI-based criterion (ΔBASDAI ≥ 50% or ≥ 2; OR 1.700, 95% CI 1.200-2.406), while the ASDAS-based criterion (ΔASDAS ≥ 1.1) showed no significant difference between sexes (OR 0.993, 95% CI 0.678-1.455), after adjusting for other baseline characteristics. CONCLUSIONS: The changes in disease activity before and after TNFi use were significantly different between sexes when measured by BASDAI, but not ASDAS. TNFi treatment effects may be interpreted differently between sexes depending on the disease activity measure used.