Identifying damage clusters in patients with systemic lupus erythematosus.

AIM: Systemic lupus erythematosus (SLE) causes irreversible damage to organ systems. Recently, evidence has been obtained for subphenotypes of SLE. This study aimed to identify damage clusters and compare the associated clinical manifestations, SLE disease activity, mortality, and genetic risk scores (GRS). METHODS: The study was conducted on the Hanyang BAE lupus cohort. Patients with disease duration <5 years were excluded to minimize confounding effects of disease duration. They were grouped into 3 clusters based on the Systemic Lupus International Collaborating Clinics Damage Index using k-means cluster analysis. RESULTS: Among the 1130 analyzed patients, musculoskeletal damage was most prevalent (20.2%), followed by ocular (11.4%), renal (10.5%), and neuropsychiatric damage (10.2%). Three significantly different damage clusters were identified. Patients in cluster 1 (n = 824) showed the least damage. Cluster 2 (n = 195) was characterized by frequent renal (55.4%) and ocular (58.0%) damage, and cluster 3 (n = 111) was dominated by neuropsychiatric (100%) and musculoskeletal damage (35.1%). Cluster 2 had the highest adjusted mean AMS (adjusted mean SLE Disease Activity Index score; mean ± SD: 5.4 ± 2.9), while cluster 3 had the highest mortality (14.4%). Weighted GRS did not differ significantly between the clusters. CONCLUSION: Patients in prevalent renal and ocular damage cluster had the highest AMS scores, while the cluster with frequent neuropsychiatric damage had the highest mortality.

Factors associated with time to diagnosis from symptom onset in patients with early rheumatoid arthritis.

BACKGROUND/AIMS: To identify the factors associated with time to diagnosis after symptom onset in patients with early rheumatoid arthritis (RA). METHODS: Early RA patients with ≤ 1 year of disease duration in the KORean Observational study Network for Arthritis (KORONA) database were included in this analysis. Patients were further divided into two groups according to the time to diagnosis from symptom onset: the early diagnosis group (time to diagnosis ≤ 1 year) and the late diagnosis group (time to diagnosis > 1 year). Using the multivariable regression model, we identified factors associated with early diagnosis. RESULTS: Among 714 early RA patients, 401 patients (56.2%) and 313 patients (43.8%) were included in the early diagnosis and late diagnosis groups, respectively. The mean disease duration was 0.47 years in the early diagnosis group and 0.45 years in the late diagnosis group. In multivariable model analysis, greater age at onset (odds ratio [OR], 1.03; 95% confidence interval [CI], 1.02 to 1.05), high school education or higher (OR, 1.68; 95% CI, 1.14 to 2.47), higher income (OR, 1.48; 95% CI, 1.05 to 2.08), and initial small joint involvement (OR, 1.42; 95% CI, 1.02 to 1.98) were factors associated with early diagnosis. At diagnosis, disease activity scores using 28 joints on diagnosis (3.81 ± 1.44 vs. 3.82 ± 1.42, p = 0.92) and functional disability (0.65 ± 0.61 vs. 0.57 ± 0.62, p = 0.07) did not different between the two groups. However, hand joint erosion on X-ray (37.8% vs. 25.6%, p < 0.01) was more common in the late diagnosis group than the early diagnosis group. CONCLUSION: Older onset age, higher educational level and income, and initial small joint involvement were positive factors for early diagnosis of RA.

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

AIM: To determine characteristics of rheumatoid arthritis (RA) patients in Korea using disease-modifying anti-rheumatic drugs (DMARDs) for at least 6 months, and to identify factors associated with poor health-related outcomes. METHOD: A total of 2000 RA patients aged > 20 years, treated with DMARDs for at least 6 months, and signed informed consent, were enrolled in this non-interventional, multicenter, cross-sectional observational study from December 2012 to June 2013. Health-related quality of life (HRQoL) was measured using EuroQuol 5D (EQ-5D) and functional disability was measured using the Korean Health Assessment Questionnaire (KHAQ). Univariate and multivariate linear regression analyses were used to determine the association between patient characteristics and patient-reported outcomes (PROs). RESULTS: Of all RA patients, 84% were female, patients with low Disease Activity Score of 28 joints erythrocyte sedimentation rate (DAS-28-ESR < 3.2) was 54%, while moderate (DAS-28-ESR 3.2-5.1) and high disease activity score (DAS-28-ESR > 5.1) were 38% and 7.6%, respectively. Mean EQ-5D index score and KHAQ score were 0.6 ± 0.28 and 0.7 ± 0.67, respectively. In multivariate analysis with both PROs, average HRQoL and functional disability score appeared to be worse in persons with older age compared to younger age (P < 0.001), and worse in females compared to males (P < 0.001). Compared to patients having lower DAS (< 3.2), those with moderate and highest DAS (3.2-5.1 and > 5.1) had worse outcome measures (P < 0.001). CONCLUSION: In this study, higher DAS was one of the most influential factors for poor PROs among all other factors. Therefore, we could suggest appropriate treatment approaches according to DAS along with other significantly associated factors with PROs in the early stage of RA.

Update on the prevalence and incidence of rheumatoid arthritis in Korea and an analysis of medical care and drug utilization.

The objectives of this study are to identify the prevalence and incidence of rheumatoid arthritis (RA) and to investigate the patterns of medical care and drug utilization by RA patients in Korea. Korean National Health Insurance claims data were used for analysis. RA patients were defined as those having an RA code from 2009 to 2012 and using disease-modifying anti-rheumatic drugs (DMARDs) within 1 year after the code. RA patients identified in 2010 with a disease-free period for 12 months before the index date, and those who received continuous treatment in 2011-2013 were defined as incident cases. Patterns of medical care and drug utilization were compared among subgroups. The prevalence of RA increased yearly from 0.28% in 2009 to 0.32% in 2012. The incidence of RA in 2010 was 28.5 per 100,000 person-years. The use of biologic DMARDs (bDMARDs) increased from 2.31% in 2009 to 4.05% in 2012. Hydroxychloroquine (57.53-62.45%) was the most commonly used the conventional DMARDs, followed by methotrexate (49.99-51.87%). The use of bDMARDs (1.39 vs. 2.43%) was less frequent in EORA patients than YORA patients. Hydroxychloroquine (74.96 vs. 72.11%) was more frequently used, but methotrexate (55.24 vs. 59.25%) and sulfasalazine (27.96 vs. 32.72%) were used less frequently in EORA patients than in YORA patients. The prevalence of RA has increased in Korea. EORA patients used fewer bDMARDs, methotrexate, and sulfasalazine but more hydroxychloroquine than YORA patients.

Isoniazid treatment for latent tuberculosis infection is tolerable for rheumatoid arthritis patients receiving tumor necrosis factor inhibitor therapy.

BACKGROUND/AIMS: To evaluate the impact of isoniazid (INH) treatment for latent tuberculosis infection (LTBI) on the development of liver function test (LFT) abnormality and the persistence of tumor necrosis factor (TNF) inhibitors in rheumatoid arthritis (RA) patients. METHODS: We retrospectively enrolled patients with RA who were treated with TNF inhibitors at a university hospital between December 2000 and November 2011. After dividing the patients into two groups based on the occurrence of LFT abnormality during follow-up, we compared demographic and clinical features between the two groups. A multivariable logistic regression analysis was performed to identify the impact of INH treatment on LFT abnormality. The impact of INH treatment on the persistence of TNF inhibitors was also evaluated with the log-rank test and the Cox-proportional hazards model. RESULTS: A total of 312 RA patients including 96 patients (30.9%) who took INH for LTBI were included in this analysis. Thirty-nine patients (12.5%) experienced LFT abnormalities while using TNF inhibitors. The use of INH was associated with LFT abnormalities (odds ratio, 3.01; 95% confidence interval [CI], 1.39 to 6.48) after adjusting for covariates, including methotrexate use. However, the persistence of TNF inhibitors over 5 years did not differ between patients receiving or not receiving INH treatment (49.4 vs. 54.6%, p = 0.79). INH treatment was not a risk factor for discontinuation of TNF inhibitors (hazard ratio, 1.01; 95% CI, 0.66 to 1.57). CONCLUSION: INH treatment for LTBI in RA patients who started TNF inhibitors is associated with the occurrence of LFT abnormality; however, it does not lead to discontinuation of TNF inhibitors.

Impact of anti-rheumatic treatment on cardiovascular risk in Asian patients with rheumatoid arthritis.

OBJECTIVES: To estimate the incidence of cardiovascular disease (CVD) in Asian patients with rheumatoid arthritis (RA) and to evaluate the impact of anti-rheumatic treatment on the development of CVD. METHODS: A retrospective cohort of Asian patients with RA was established to identify the incidence rate (IR) of CVD in RA patients. The cohort was generated using the Korean National Healthcare claims database, which contained claims from Jan 2009 to Dec 2013. A total of 137,512 RA patients were identified; individuals with a history of CVD for 6 months or more before the index date were excluded. Nested case-control samples were drawn from the full study population with a case:control ratio of 1:4 (n = 7102 cases; n = 27,018 controls without CVD). A conditional multivariate regression model was used to evaluate the impact of anti-rheumatic treatment on the development of CVD in RA patients after matching for age, sex, RA index date, comorbidities, and drug use (e.g., antiplatelet agents and cholesterol-lowering agents). RESULTS: The IR for development of overall CVD in RA patients was 182.1 (95% CI: 178.4-185.9) per 10,000 person-years. In models adjusted for other CVD risk factors, disease-modifying anti-rheumatic drugs (DMARDs) (OR = 0.79) were protective against CVD, and biologic DMARDs were not significantly associated with CVD risk (OR = 0.85). Corticosteroids (OR = 1.26) and NSAIDs (nonselective NSAIDs: OR = 1.32, Cox-2 inhibitors: OR = 1.31) were risk factors for CVD in RA patients. CONCLUSIONS: The use of DMARDs is protective against CVD, while corticosteroids and NSAIDs increased the risk of CVD in RA patients.

Characteristics and outcomes of rheumatoid arthritis patients who started biosimilar infliximab.

To compare the characteristics of rheumatoid arthritis (RA) patients receiving either biosimilar or originator infliximab and to identify the effectiveness and safety of biosimilar infliximab in RA patients in real-world practice. RA patients who started either biosimilar or originator infliximab were selected using the prospective biologic disease-modifying anti-rheumatic drugs (DMARDs) registry: BIOlogics Pharmacoepidemiologic StudY (BIOPSY). Baseline characteristics of the two groups were compared, and short-term treatment outcomes, including DAS28-ESR and HAQ-DI scores, were compared after initiation of biosimilar or originator infliximab. The drug retention rates of the two groups were also compared. A total of 100 RA patients, 55 biosimilar, and 45 originator infliximab users were included in this analysis. Baseline characteristics of age, disease duration, and previous or current medications were similar in the two groups. Baseline DAS28-ESR was higher in the originator infliximab group (6.3 ± 1.1 vs. 5.8 ± 1.1, p = 0.02). The early DAS28-ESR remission rates observed 7.9 ± 1.8 months after starting biosimilar and originator infliximab were 15.0 and 25.0%, respectively (p = 0.47). The change in HAQ-DI did not differ between the two groups (0.4 ± 0.7 vs. 0.4 ± 0.8, p = 0.94). Patients treated with biosimilar infliximab in clinical practice had lower disease activity at the start of treatment than those receiving originator infliximab. Biosimilar infliximab was well-tolerated, safe, and of similar clinical effectiveness to originator infliximab. Larger number of patient and longer follow-up data will be needed to confirm the effectiveness and safety of biosimilar infliximab in clinical practice.

Safety of resuming biologic DMARDs in patients who develop tuberculosis after anti-TNF treatment.

OBJECTIVES: To estimate the incidence of tuberculosis (TB) in rheumatoid arthritis (RA) patients treated with tumor necrotizing factor inhibitor (TNFI) and evaluate the safety of resuming biologic disease-modifying anti-rheumatic drugs (DMARDs) in patients who developed TB after anti-TNF treatment. METHODS: We conducted an inception cohort study of RA patients in the Korean Healthcare Claims Database who started TNFI as the first biologic DMARD between January 2009 and December 2013. The incidence rate (IR) of TB was estimated among total TNFI starters and a nested case-control analysis was performed to compare the characteristics of patients who developed TB and those did not. Patients diagnosed with relapsed TB after resuming biologic DMARDs were identified and their features were described. RESULTS: We included 4638 RA patients who started TNFI, contributing 8542 PYs of follow-up. The IR of TB in TNFI users was 1.10 (CI: 0.86-1.34) per 100 PYs. After the initial 6 months, the IR was highest at 1.56 (CI: 1.02-2.10) and decreased gradually over time. Among the 81 patients who developed TB, 30 patients (37.0%) resumed biologic DMARDs with a mean interval of 3.3 months after TB development. Two cases of TB were detected among 30 patients with an observational period of 45.7 PY. CONCLUSIONS: The IR of TB in RA patients who started TNFI was 1.10 per 100 PYs. This rate was highest during the first 6 months. Resumption of biologic DMARDs requires careful monitoring for TB relapse.

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.

Impact of early diagnosis on functional disability in rheumatoid arthritis.

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

Drug retention and safety of TNF inhibitors in elderly patients with rheumatoid arthritis.

BACKGROUND: The concerns about the development of adverse events (AEs) in elderly RA patients as a result of age-related changes in drug metabolism and the presence of comorbid illnesses are emphasizing due to increasing prevalence of rheumatoid arthritis (RA) in old age. However, they tend to be inadequately represented in RA clinical trials because of the exclusion criteria that are commonly applied. The tolerability and safety of TNF inhibitors in elderly patients have not been also evaluated in clinical practice. This study aimed to evaluate the retention rate and safety of TNF inhibitors (TNFI) in elderly RA patients. METHODS: Total 429 RA patients (838 person-years [PYs]) treated with TNFI from a retrospective biologic DMARDs registry. Patients were divided into an elderly (age ≥60 years) and a younger group (<60 years). The drug retention rates of both groups were compared using Kaplan-Meier curves. Potential predictors of TNFI discontinuation in the elderly were examined using Cox regression analysis. The incidence rate (IR) of serious adverse events (SAEs) in the elderly group was compared to that of the young group. RESULTS: Of the patients, 24.9 % (n = 107, 212 PYs) were in the elderly group. Regarding the retention rates of TNFI in 3 years, there was no significant difference between the elderly and younger group (p = 0.33). The major cause of discontinuation in elderly patients was AE (34.3 %), whereas that was drug ineffectiveness (41.7 %) in younger patients. Age (HR 1.09, CI 1.02-1.16) was a predictor of discontinuation, while the presence of comorbidity (HR 0.37, CI 0.15-0.91) had a protective effect against drug discontinuation in the elderly. The IR of SAEs in the elderly (6.13/100 PYs) was higher than in the younger group (5.11/100 PYs). CONCLUSIONS: The retention rate of TNFI in the elderly was comparable with that in younger patients. The major cause of discontinuation in the elderly patients was AEs, while it was drug ineffectiveness in younger patients. The IR of SAEs in the elderly was higher than in the younger patients.

Differences in Clinical Features and Mortality between Childhood-onset and Adult-onset Systemic Lupus Erythematosus: A Prospective Single-center Study.

OBJECTIVE: To compare clinical features and mortality between childhood-onset systemic lupus erythematosus (cSLE) and adult-onset SLE (aSLE) in a prospective single-center cohort. METHODS: A total of 1112 patients with SLE (133 cSLE and 979 aSLE) were enrolled and followed from 1998 to 2012. The 2 groups were compared regarding American College of Rheumatology (ACR) classification criteria for SLE, autoantibodies, disease activity measured by the Adjusted Mean SLE Disease Activity Index (AMS), damage measured by the Systemic Lupus International Collaborating Clinics/ACR Damage Index (SDI), and medication. The standardized mortality ratio (SMR) was calculated. Predictors of mortality in SLE were evaluated using Cox proportional hazard models. RESULTS: After a mean followup of 7.6 years, patients with cSLE had a higher number of cumulative ACR criteria and a higher AMS (p < 0.001 each), but there was no difference in SDI (p = 0.797). Immunosuppressants were used more frequently by patients with cSLE (p < 0.001). The SMR of cSLE was 18.8 (95% CI 8.6-35.6), significantly higher than that of aSLE (2.9, 95% CI 2.1-3.9). We found cSLE to be an independent predictor of mortality (HR 3.6, p = 0.008). Moreover, presence of hemolytic anemia (7.2, p = 0.034) and antiphospholipid antibody (aPL; 3.8, p = 0.041) increased the magnitude of risk of early mortality more in the patients with cSLE than in those with aSLE. CONCLUSION: The clinical course of cSLE as measured by number of clinical manifestations and disease activity is worse than that of aSLE. Also, cSLE patients with hemolytic anemia and aPL are at greater risk of death than patients with aSLE who have those features.

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 Associated with the Use of Complementary and Alternative Medicine for Korean Patients with Rheumatoid Arthritis.

OBJECTIVE: Rheumatoid arthritis (RA) is a chronic autoimmune disease that is often painful and debilitating. Patients with RA are increasingly receiving complementary and alternative medicine (CAM). We aimed to identify the patient characteristics and disease-specific factors associated with Korean patients with RA who decide to start treatment with CAM. METHODS: Among the total 5371 patients with RA in the KORean Observational study Network for Arthritis (KORONA), 2175 patients who had no experience with CAM were included in our study. In our study, we assessed the frequency of new incident CAM use, its patterns, and the predictive factors of new CAM use. RESULTS: Of the 2175 patients, 229 patients (10.5%) newly started receiving CAM within a year of enrolling in the cohort. Of those who started treatment with CAM, 17.0% received only herbal medicine, 54.6% only acupuncture treatments (7.0% used a combination of both), and 21.4% "Other" (e.g., physical therapy and placental extract injections). Women (OR 1.89, 95% CI 1.13-3.14) and patients with depression (OR 3.52, 95% CI 1.65-7.50) were significantly more likely to be treated with CAM. Regarding household types, patients who lived in an extended family (OR 1.78, 95% CI 1.08-2.95) or as part of a couple (OR 1.55, 95% CI 1.07-2.24) were more likely to be treated with CAM than patients living in a nuclear family. CONCLUSION: Our study found, within a year, an incidence rate of 10.5% for new CAM use among patients with no previous experience with CAM. Sex, depression, and household type were significantly associated with new CAM use.

Evaluation of the usefulness of interferon-gamma release assays and the tuberculin skin test for the detection of latent Mycobacterium tuberculosis infections in Korean rheumatic patients who are candidates for biologic agents.

AIM: The aim of this study was to evaluate the occurrence of active tuberculosis (TB) in patients who received both an interferon-gamma release assay (the QuantiFERON-TB Gold In-Tube test [QFT-GIT]) and tuberculin skin test (TST) in comparison with those who received QFT-GIT or TST alone for the detection of latent TB infection (LTBI). METHODS: In total, 842 patients who received QFT-GIT or TST and used biologic agents between January 2007 and December 2012 were recruited to determine the usefulness of LTBI screening tests. The incidence of active TB was calculated relative to the LTBI screening method as the number of events per 100 000 person-years exposure. RESULTS: TB occurred in two of the patients who complied with an LTBI prophylaxis strategy. The TB incidence in the group that received both QFT-GIT and TST was 151.05 (95% confidence interval [CI] 150.11-151.98)/100 000 person-years, and the incidence was 169.78 (95% CI 168.73-170.84)/100 000 person-years in the group that received only TST. CONCLUSION: TB occurred even in some patients who received LTBI prophylaxis in compliance with national guidelines. The incidence of TB in patients who received either the QFT-GIT plus TST prophylaxis strategy or the TST prophylaxis strategy alone was higher than the annual incidence of the general population of the Republic of Korea. It is not possible to conclude which of the LTBI prophylaxis strategies is superior.

A comparison of incidence and risk factors for serious adverse events in rheumatoid arthritis patients with etanercept or adalimumab in Korea and Japan.

OBJECTIVE: To compare the incidence and risk factors of serious adverse events (SAEs) in rheumatoid arthritis (RA) patients treated with etanercept (ETN) or adalimumab (ADA) between Korean and Japanese registries. METHODS: We recruited 416 RA patients [505.2 patient-years (PYs)] who started ETN or ADA from Korean registry and 537 RA patients (762.0 PY) from Japanese registry. The patient background, incidence rate (IR) of SAE in 2 years, and risk factors for SAEs were compared. RESULTS: Korean patients were younger and used more nonbiologic DMARDs, higher doses of methotrexate, and lower doses of prednisolone (PSL). The IR of SAEs (/100 PY) was higher in the Japanese registry compared to the Korean [13.65 vs. 6.73]. In both registries, infection was the most frequently reported SAE. The only significant risk factor for SAEs in Korean registry was age by decade [1.45]. In Japanese registry, age by decade [1.54], previous use of nonbiologic DMARDs ≥ 4 [1.93], and concomitant use of oral PSL ≥ 5 mg/day [2.20] were identified as risk factors for SAEs. CONCLUSIONS: The IR of SAE in Japan, especially infection, was higher than that of Korea, which was attributed to the difference of demographic and clinical characteristics of RA patients and treatment profiles.

Simultaneous detection of antibacterial sulfonamides in a microfluidic device with amperometry.

A highly sensitive and robust method for simultaneous detection of five sulfonamide drugs is developed by integrating the preconcentration and separation steps in a microfluidic device. An ampetrometry is performed for the selective detection of sulfonamides using an aluminum oxide-gold nanoparticle (Al(2)O(3)-AuNPs) modified carbon paste (CP) electrode at the end of separation channel. The preconcentration capacity of the channel is enhanced by using the field amplified sample stacking and the field amplified sample injection techniques. The experimental parameters affecting the analytical performances, such as pH, % of Al(2)O(3), volume of AuNPs, buffer concentration, and water plug length are optimized. A reproducible response is observed during the multiple injections of samples with RSDs<4%. The calibration plots are linear with the correlation coefficient between 0.991 and 0.997 over the range between 0.01 and 2025pM. The detection limits of five drugs are determined to be between 0.91 (±0.03) and 2.21 (±0.09)fM. The interference effects of common biological compounds are also investigated and the applicability of the method to the direct analysis of sulfonamides in real meat samples is successfully demonstrated. Long term stability of the modified electrode was also investigated.

Physical activity level and risk of death: the severance cohort study.

BACKGROUND: Physical activity decreases deaths from cardiovascular disease and other causes; however, it is unclear whether physical activity is associated with cancer incidence and death in Asian populations. METHODS: Data from 59 636 Koreans aged 30 to 93 years were collected using a questionnaire and medical examination at the Severance Hospital Health Promotion Center between 1994 and 2004. Study participants were followed for a mean duration of 10.3 years. RESULTS: In the exercising group, the multivariate Cox proportional hazards model showed a lower risk of cancer death (hazard ratio [HR] = 0.72, 95% CI = 0.62-0.85) in men but not in women. Those who exercised, as compared with those who did not, had lower risks of all-cause death (men: HR = 0.68, 95% CI = 0.60-0.76; women: HR = 0.65, 95% CI = 0.53-0.79) and noncancer death (men: 0.63, 0.53-0.75; women: 0.52, 0.39-0.69). Physical activity was inversely associated with risk of noncancer death among men and women. CONCLUSIONS: Physical activity was associated with lower risks of cancer death and noncancer death.

Effects of a combined lifestyle score on 10-year mortality in Korean men and women: a prospective cohort study.

BACKGROUND: Most studies that have evaluated the association between combined lifestyle factors and mortality outcomes have been conducted in populations of Caucasian origin. The objective of this study was to examine the association between combined lifestyle scores and the risk of mortality in Korean men and women. METHODS: The study population included 59,941 Koreans, 30-84 years of age, who had visited the Severance Health Promotion Center between 1994 and 2003. Cox regression models were fitted to establish the association between combined lifestyle factors (current smoker, heavy daily alcohol use, overweight or obese weight, physical inactivity, and unhealthy diet) and mortality outcomes. RESULTS: During 10.3 years of follow-up, there were 2,398 cases of death from any cause. Individual and combined lifestyle factors were found to be associated with the risk of mortality. Compared to those having none or only one risk factor, in men with a combination of four lifestyle factors, the relative risk for cancer mortality was 2.04-fold, for non-cancer mortality 1.92-fold, and for all-cause mortality 2.00-fold. In women, the relative risk was 2.00-fold for cancer mortality, 2.17-fold for non-cancer mortality, and 2.09-fold for all-cause mortality. The population attributable risks for all-cause mortality for the four risk factors combined was 44.5% for men and 26.5% for women. CONCLUSION: This study suggests that having a high (unhealthy) lifestyle score, in contrast to a low (healthy) score, can substantially increase the risk of death by any cause, cancer, and non-cancer in Korean men and women.

Impact of metabolic syndrome independent of insulin resistance on the development of cardiovascular disease.

BACKGROUND: It is controversial as to whether metabolic syndrome is a predictor of cardiovascular disease (CVD) independent of insulin resistance (IR). The aim of this study was to determine the independent and combined effects of metabolic syndrome and IR on the incidence of CVD in a prospective cohort study. METHODS AND RESULTS: A total of 6,430 healthy subjects who underwent a health check-up were enrolled. Risk factors for atherosclerotic CVD (ASCVD) including ischemic heart disease (IHD) and stroke were measured. The prevalence of metabolic syndrome and IR were 24.4% and 25.6%, respectively. There were 644 incident cases (9.0%) of ASCVD diagnosed in the cohort. After adjusting for traditional confounders and IR, metabolic syndrome was related to the incidence of CVD. In the multivariate model, the hazard ratios (95% confidence intervals) of metabolic syndrome for IHD, stoke, and ASCVD were 1.66 (1.32-2.09), 1.60 (1.21-2.12), and 1.61 (1.36-1.90), respectively. The risk of IHD, stoke, and ASCVD increased with increasing number of metabolic syndrome components. Furthermore, the risk of CVD was stronger in those who had both metabolic syndrome and IR concurrently. CONCLUSIONS: Metabolic syndrome is related to the incidence of CVD independent of IR. Also, the combined effect of metabolic syndrome and IR contributes to the risk of CVD.