Fracture Risk and Its Prevention Patterns in Korean Patients with Polymyalgia Rheumatica:a Retrospective Cohort Study

Background@#To evaluate the incidence of fractures and fracture risk factors in Korean patients with polymyalgia rheumatica (PMR). @*Methods@#All PMR patients who visited a rheumatology clinic at a tertiary referral hospital between March 2005 and March 2018 were retrospectively assessed. We estimated bone mineral density (BMD) screening rate within 6 months of the first visit and classified the patients according to the performance and results of BMD screening. Incidence rates (IRs) of fractures were calculated in each group and risk factors for fractures were identified using Poisson regression analysis. @*Results@#A total of 95 PMR patients with median (interquartile range) age of 64.0 (56.0–72.0) years were included. Baseline BMD was assessed in only 55.8% of these patients (n = 53); 24 patients with osteoporosis, 20 with osteopenia, and 9 with normal BMD. During 433.1 person-years (PYs) of observation, 17 fractures occurred in 12 patients (IR, 3.93 [95% confidence interval (CI), 2.46–6.26]/100 PYs); 8.32 (95% CI, 4.09–16.90)/100 PYs in the osteopenia group, 3.40 (95% CI, 1.30–8.90)/100 PYs in the osteoporosis group, and 3.37 (95% CI, 1.53–7.39)/100 PYs in the no BMD test group. Risk factors for fractures were female sex, advanced age (≥ 65 years), longer follow-up duration, initial glucocorticoid dose ≥ 10 mg/day, and higher cumulative glucocorticoid dose over the first 6 months. @*Conclusion@#The incidence rate of fractures in Korean patients with PMR was 3.93/100 PYs. Female sex, advanced age, longer follow-up duration, and increased glucocorticoid dose are risk factors for osteoporotic fracture.

KOBIO, the First Web-based Korean Biologics Registry Operated With a Unified Platform Among Distinct Disease Entities

The KOrean College of Rheumatology BIOlogics and targeted therapy (KOBIO) registry is a nationwide observational cohort that captures detailed data on exposure of patients to biologic and targeted synthetic disease-modifying anti-rheumatic drugs (DMARDs). This registry was launched in December 2012 with an aim to prospectively investigate clinical manifestations and outcomes of patients with rheumatoid arthritis (RA), ankylosing spondylitis, and psoriatic arthritis who initiated a biologic or targeted synthetic DMARD or switched to another. Demographic data, disease activity, current treatment, adverse events, terms based on Medical Dictionary for Regulatory Activities, and so on are registered for patients who are then followed up annually in a web-based unified platform. The KOBIO registry also recruits and collects data of patients with RA on conventional DMARDs for comparison. As of today, more than 5,500 patients were enrolled from 47 academic and community Rheumatology centers across Korea. The KOBIO registry has evolved to become a powerful database for clinical research to improve clinical outcomes and quality of treatment.

Clinical and Genetic Risk Factors Associated With the Presence of Lupus Nephritis

Objective@#To elucidate whether clinical features and the weighted genetic risk score (wGRS) were associated with the presence of lupus nephritis (LN). @*Methods@#We retrospectively divided patients with systemic lupus erythematosus (SLE, n=1,078) into biopsy-proven LN (n=507) and non-LN groups (non-LN, n=571). Baseline clinical features, serologic markers, and the wGRS were collected. The wGRS was calculated from 112 non-human leukocyte antigen (non-HLA) loci and HLA-DRβ1 amino acid haplotypes for SLE. Associations among clinical features, wGRS, and the presence of LN were identified. @*Results@#In the multivariate analysis, patients with LN were younger at diagnosis (odds ratio [OR]=0.97, p＜0.001), had more pleuritis (OR=2.44, p＜0.001) and pericarditis (OR=1.62, p=0.029), had a higher detection rate of anti-double stranded deoxyribonucleic acid (anti-dsDNA antibodies, OR=2.22, p＜0.001), anti-Smith antibodies (anti-Sm antibodies, OR=1.70, p=0.002), low level of complement (OR=1.37, p=0.043) and absence of antiphospholipid antibodies (aPL antibodies, OR=1.60, p=0.002), and had higher wGRS (OR=1.16, p=0.012). Mediation analysis suggested that anti-Sm antibodies and low complement could be mediators in the relationship between high wGRS and the presence of LN. @*Conclusion@#Onset age, pleuritis, pericarditis, several serologic markers, and wGRS were associated with the presence of LN. Anti-Sm antibodies and low complement appeared to mediate the indirect relationship between wGRS and the presence of LN.

KOBIO, the First Web-based Korean Biologics Registry Operated With a Unified Platform Among Distinct Disease Entities

The KOrean College of Rheumatology BIOlogics and targeted therapy (KOBIO) registry is a nationwide observational cohort that captures detailed data on exposure of patients to biologic and targeted synthetic disease-modifying anti-rheumatic drugs (DMARDs). This registry was launched in December 2012 with an aim to prospectively investigate clinical manifestations and outcomes of patients with rheumatoid arthritis (RA), ankylosing spondylitis, and psoriatic arthritis who initiated a biologic or targeted synthetic DMARD or switched to another. Demographic data, disease activity, current treatment, adverse events, terms based on Medical Dictionary for Regulatory Activities, and so on are registered for patients who are then followed up annually in a web-based unified platform. The KOBIO registry also recruits and collects data of patients with RA on conventional DMARDs for comparison. As of today, more than 5,500 patients were enrolled from 47 academic and community Rheumatology centers across Korea. The KOBIO registry has evolved to become a powerful database for clinical research to improve clinical outcomes and quality of treatment.

Clinical and Genetic Risk Factors Associated With the Presence of Lupus Nephritis

Objective@#To elucidate whether clinical features and the weighted genetic risk score (wGRS) were associated with the presence of lupus nephritis (LN). @*Methods@#We retrospectively divided patients with systemic lupus erythematosus (SLE, n=1,078) into biopsy-proven LN (n=507) and non-LN groups (non-LN, n=571). Baseline clinical features, serologic markers, and the wGRS were collected. The wGRS was calculated from 112 non-human leukocyte antigen (non-HLA) loci and HLA-DRβ1 amino acid haplotypes for SLE. Associations among clinical features, wGRS, and the presence of LN were identified. @*Results@#In the multivariate analysis, patients with LN were younger at diagnosis (odds ratio [OR]=0.97, p＜0.001), had more pleuritis (OR=2.44, p＜0.001) and pericarditis (OR=1.62, p=0.029), had a higher detection rate of anti-double stranded deoxyribonucleic acid (anti-dsDNA antibodies, OR=2.22, p＜0.001), anti-Smith antibodies (anti-Sm antibodies, OR=1.70, p=0.002), low level of complement (OR=1.37, p=0.043) and absence of antiphospholipid antibodies (aPL antibodies, OR=1.60, p=0.002), and had higher wGRS (OR=1.16, p=0.012). Mediation analysis suggested that anti-Sm antibodies and low complement could be mediators in the relationship between high wGRS and the presence of LN. @*Conclusion@#Onset age, pleuritis, pericarditis, several serologic markers, and wGRS were associated with the presence of LN. Anti-Sm antibodies and low complement appeared to mediate the indirect relationship between wGRS and the presence of LN.

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.@*CONCLUSIONS@#Older onset age, higher educational level and income, and initial small joint involvement were positive factors for early diagnosis of RA.

Antineutrophil Cytoplasmic Antibody-Associated Vasculitis in Korea: A Narrative Review

Antineutrophil cytoplasmic antibody-associated vasculitis (AAV) is a group of systemic necrotising vasculitides, which often involve small vessels, and which lead to few or no immune deposits in affected organs. According to clinical manifestations and pathological features, AAV is classified into three variants: microscopic polyangiitis, granulomatosis with polyangiitis (GPA), and eosinophilic GPA. The American College of Rheumatology 1990 criteria contributed to the classification of AAV, although currently the algorithm suggested by the European Medicines Agency in 2007 and the Chapel Hill Consensus Conference Nomenclature of Vasculitides proposed in 2012 have encouraged physicians to classify AAV patients properly. So far, there have been noticeable advancements in studies on the pathophysiology of AAV and the classification criteria for AAV in Western countries. However, studies analysing clinical features of Korean patients with AAV have only been conducted and reported since 2000. One year-, 5 year-, and 10 year-cumulative patient survival rates are reported as 96.1, 94.8, and 92.8%. Furthermore, initial vasculitis activity, prognostic factor score, age and specific organ-involvement have been found to be associated with either all-cause mortality or poor disease course. The rate of serious infection is 28.6%, and 1 year-, 5 year- and 10 year-cumulative hospitalised infection free survival rates range from 85.1% to 72.7%. The overall standardised incidence ratio of cancer in AAV patients was deemed 1.43 compared to the general Korean population.

Fate of Abstracts Presented at the Korean College of Rheumatology Annual Scientific Meetings

OBJECTIVE: To evaluate the fate of abstracts presented at scientific meetings of the Korean College of Rheumatology (KCR). METHODS: This study examined the abstracts presented at annual meetings of the KCR from 2005 to 2014. Only original studies were selected, excluding case reports. A manual search was conducted using PubMed, KoreaMed, Cochrane Library, and Embase to track the published articles. The abstracts were considered to have been published if the authors, title, study design, and results were the same for a published article. In addition, they were considered published if the author and the study design matched, even if the results of the abstract and the results of the published articles were not identical. RESULTS: A total of 928 abstracts from 2005 to 2014 were analyzed. Of the 928 abstracts, 468 (50.43%) abstracts were published in a peer-reviewed journal and the mean time to publication was 19 months. Of the 468 abstracts, 414 were published in a science citation index extended (SCI[E]) journal, and 54 were published in non-SCI(E) journals. The proportion of SCI(E) articles increased annually. The average impact factor for the SCI(E) journals was 2.93. In subgroup analysis, the abstracts that were awarded the best oral or best poster presentation were more likely to be published as full-length articles with a higher impact factor than the abstracts not awarded. CONCLUSION: Half of the abstracts presented in the KCR annual meetings were published in a peer-reviewed journal. Approximately 90% of the articles were published in a SCI(E) journal.

Eosinophilic Granulomatosis with Polyangiitis: Experiences in Korean Patients

Eosinophilic granulomatosis with polyangiitis (EGPA) is one form of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis. Identical to what has been called Churg-Strauss syndrome, EGPA exhibits both allergic and vasculitis features. EGPA was first described as a syndrome consisting of asthma, fever, eosinophilia, and organ involvement including heart failure, neuropathy, and kidney damage, by Churg and Strauss in 1951. On the basis of the 2012 Chapel Hill Consensus Conferences Nomenclature of Vasculitis, EGPA comprises three typical allergic components, including asthma, peripheral eosinophilia, and eosinophil-rich granuloma of the respiratory tracts. EGPA has three clinical and histological stages. The first is an allergic stage composed of asthma and sinusitis, and the second is an eosinophilic stage characterised by peripheral hypereosinophilia and intra-organ infiltration of eosinophils. The last is a vasculitic stage, including necrotising inflammation of small vessels and end-organ damage. In this review, we describe the classification criteria for EGPA and recommendations for the evaluation and management of EGPA with conventional and newly suggested drugs for EGPA. Also, we discuss a variety of clinical aspects such as predictive values for prognosis and associations with other Th2-mediated diseases and hepatitis B virus.

Prevalence and Associated Factors for Non-adherence in Patients with Rheumatoid Arthritis

OBJECTIVE: To estimate the prevalence of non-adherence to rheumatoid arthritis (RA) medication and identify the associated factors for non-adherence in RA patients. METHODS: Among the KORean Observational study Network for Arthritis 3,523 patients who completed a questionnaire about the adherence to RA medication were analyzed. The patients were divided into two groups: 1) adherent group, patients who skipped medication ≤5 days within the past 2 months; and 2) non-adherent group, patients who skipped ≥6 days of medication. The baseline characteristics were compared, and multivariable regression analysis was performed to identify the associated factors for non-adherence. RESULTS: The non-adherent group had 339 patients (9.6%). The common causes of non-adherence were forgetfulness (45.8%), absence of RA symptoms (24.7%), and discomfort with RA medication (13.1%). Younger age (odds ratio [OR] 1.02, p < 0.01) and higher income (OR 1.70, p < 0.01) were associated with an increased risk of non-adherence. Whereas higher functional disability (OR 0.68, p < 0.01) and oral corticosteroid use (OR 0.73, p=0.02) were associated with a decreased risk of non-adherence. The associated factors differed according to cause of non-adherence. Having adverse events (OR 2.65, p=0.02) was associated with the risk of non-adherence due to discomfort with RA medication while a higher level of education (OR 2.37, p=0.03) was associated with the risk of non-adherence due to an absence of RA symptoms. CONCLUSION: The 9.6% of Korean RA patients were non-adherent to RA medication. The associated factors differed according to the cause of non-adherence. Therefore, an individualized approach will be needed to improve the adherence to RA medication.

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 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.

Long-term Outcomes of Autologous Peripheral Blood Stem Cell Transplantation for Refractory Rheumatic Diseases

OBJECTIVE: We investigated the long-term outcomes of autologous peripheral blood stem cell transplantation (PBSCT) to treat refractory rheumatic diseases. METHODS: Patients who underwent PBSCT for refractory rheumatic diseases at our institution between 2002 and 2005 were assessed for outcomes including treatment response, adverse events, damage accrual, and survival at 6 months and last follow-up. RESULTS: Eleven patients, including six with systemic lupus erythematosus (SLE), four with systemic sclerosis (SSc), and one with Still's disease were treated with PBSCT. In SLE patients, two showed complete response, two partial response, and two expired. One patient who expired responded completely two months after transplantation but discontinued treatment by choice and expired at six months due to an SLE flare. Long-term, two patients went into remission without organ damage, one patient went into remission with organ damage, and one had low disease activity with organ damage. Of the four patients with SSc, two showed a complete response, one a partial response, and there was one transplantation-related death at six months. At the last record notation, two remained in remission without relapse and one was lost to follow-up. The Still's disease patient partially responded at six months and was in remission at the last record notation. CONCLUSION: The ten-year survival rate was 70% with a 40% recurrence rate and 20% treatment-related mortality rate.

Agreement of Major Diagnosis and Comorbidity between Self-reported Questionnaire and Medical Record Review in Patients with Rheumatic Disease

OBJECTIVE: Self-report questionnaires are frequently used to obtain information in epidemiological research. However, information reported by patients are sometimes inconsistent with medical records. This study compared self-reported major rheumatologic diagnoses and co-morbid conditions with those from a medical record review. METHODS: A cross-sectional survey was conducted at two tertiary academic hospitals. All patients who visited the rheumatology department from September 2, 2009 to September 13, 2009 were enrolled in this survey. Structured patient questionnaires and medical record reviews were performed in each hospital. We evaluated agreement with kappa statistics (κ) between these two data sources for major rheumatologic diagnosis and Charlson Comorbidity Index (CCI) score. Multiple logistic regression models were used to investigate factors associated with disagreement. RESULTS: A total of 369 patients were interviewed at clinic exit. Of them, 302 patients (81.8%) were female, and the average age was 52.1 years. The agreement for major rheumatologic diagnosis between the questionnaire and patient chart was good (κ=0.763). The agreement rate for all rheumatic diseases was 81.8%; rheumatoid arthritis with 94.9%, systemic lupus erythematosus with 96.3%, and ankylosing spondylopathy with 100%. Higher educational level and longer attendance at our clinic were associated with agreement between major rheumatologic diagnoses. The agreement rate for CCI score between the data sources was 76.1%. CONCLUSION: In patients with rheumatologic diseases, the agreement for major diagnoses between self-reports and the medical record review was good, although it varied with the specific disease and patient characteristics. Comparing major rheumatologic diagnoses, the agreement rate for CCI was low.

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.

Prevalence and possible causes of hypouricemia at a tertiary care hospital

BACKGROUND/AIMS: We aimed to investigate the prevalence and possible causes of hypouricemia in the Korean population and to compare our findings with published results of other populations. METHODS: We examined the serum uric acid levels of 30,757 subjects who had their uric acid values measured at least once during a 1-year period. All individuals with hypouricemia (serum uric acid < 2.0 mg/dL, n = 424) were reviewed with respect to medical drug history and concomitant diseases previously identified as being associated with hypouricemia. RESULTS: The prevalence of hypouricemia was 4.14% (299/7,223) among inpatients and 0.53% (125/23,534) among outpatients, for an overall prevalence of 1.39% (424/30,757). Possible causes associated with hypouricemia were found to be solid or hematologic malignancies (n = 86), diabetes mellitus (n = 56), and therapeutic drugs (n = 29). The medications were allopurinol (n = 11), angiotensin II receptor blockers (n = 10), salicylates (n = 6), febuxostat (n = 1), and warfarin (n = 1). In the remaining 226 individuals, the cause of hypouricemia was not identified. CONCLUSIONS: Hypouricemia is relatively common in the Korean population compared to those of other countries. The possible causes associated with hypouricemia are related to underlying diseases and medications.

Gastrointestinal Risk Factors and Non-steroidal Anti-inflammatory Drugs Use in Rheumatoid Arthritis and Osteoarthritis Patients in Korea

OBJECTIVE: The aim of this study was to examine and compare the gastrointestinal (GI) risk factors and treatment patterns of rheumatoid arthritis (RA) and osteoarthritis (OA) patients in Korea. METHODS: This was a cross-sectional, observational study on RA and OA patients taking non-steroidal anti-inflammatory drugs (NSAIDs) for at least 1 month. A total of 1,896 patients (981 RA patients, 915 OA patients) were recruited from 20 university hospitals. Data were collected through medical records and patient surveys. GI risk factors included age, prolonged (over 3 months) or high-dose use of NSAIDs, alcohol drinking, smoking, use of aspirin, anticoagulants or glucocorticoids, comorbidities, and history of Helicobacter pylori infection or other GI complications. Treatment patterns were classified according to groups using, selective cyclooxygenase (COX)-2 inhibitors+/-gastro-protective agents, non-selective COX-2 inhibitors+proton pump inhibitor, or non-selective COX-2 inhibitors+/-other gastro-protective agents. RESULTS: GI risk factors were highly present in both RA and OA patients. The proportion of prolonged use of NSAIDs, smoking, and glucocorticoid use were higher in RA patients (p<0.001). The proportion of comorbidities and use of aspirin were higher in OA patients (p<0.001). The remaining GI risk factors were present in similar proportions in both groups. Use of selective COX-2 inhibitors or gastro-protective agents was higher in RA patients. CONCLUSION: Prolonged use of NSAIDs and concomitant glucocorticoid use were higher in RA patients, while comorbidities and concomitant aspirin use were predominant in OA patients. These results will provide insights for use in development of future guidelines for proper selection of NSAIDs and effective prevention of GI complications in arthritis patients.

Incidence of Tuberculosis in Rheumatoid Arthritis Patients Using Anti-Tumor Necrosis Factor Agents following Latent Tuberculosis Infection Screening Strategies

OBJECTIVE: To compare the incidence of tuberculosis (TB) in rheumatoid arthritis (RA) patients using tumor necrosis factor (TNF) inhibitors following two strategies for latent tuberculosis infection (LTBI) screening: Tuberculin skin test (TST) only vs. TST plus Qauntiferron-TB gold in tube (QFT-GIT). METHODS: Data was extracted from a retrospective cohort of Korean RA patients who used biologic agents. Of the 406 RA patients who underwent TST before starting TNF inhibitor, we selected 355 patients who strictly followed LTBI screening and treatment strategies. Two hundred and twenty-two patients were classified as TST only group and the remaining 133 patients as TST plus QFT-GIT group. We calculated the standardized incidence ratio of TB in the entire sample and compared the TB incidence between groups. RESULTS: Among the patients who received the TST only strategy (n=222, 538.6 person-year [PY]), two patients developed TB during anti-TNF therapy, while of those who followed the TST plus QFT-GIT strategy, none developed TB (n=133, 108.8 PY). The overall crude incidence of TB in RA patients using TNF inhibitors was 314 per 100,000 PY. Compared with the general population, the overall age standardized incidence of TB in TNF inhibitor users who followed management guideline for LTBI was 3.9. CONCLUSION: Despite following screening and management guidelines for LTBI, TB incidence for RA patients during anti-TNF therapy is higher than in the general population. Combining QFT-GIT with TST as a screening for LTBI might be reduce the risk of TB.

Prediction for TNF Inhibitor Users in RA Patients According to Reimbursement Criteria Based on DAS28

OBJECTIVE: The purpose of this study is to examine the difference between the numbers of patients in rheumatoid arthritis (RA) who are eligible to TNF inhibitors by the past Korean National Health Insurance reimbursement guideline and by the disease activity score with 28-joint assessment (DAS28) based criteria. METHODS: Data were obtained from a multi-center registry for biologics users in Korean RA patients, BIOlogics Pharmacoepidemiologic StudY (BIOPSY). DAS28 was calculated based on either ESR or CRP, and DAS28 of more than 5.1 or between 3.2 and 5.1 with radiographic changes was defined as a cut-off point for the initiation of TNF inhibitors. For the maintenance criteria, we used both of improving in DAS28 score (>1.2) and low disease activity (DAS 28<3.2). Differences between the numbers in each step by two criteria were described with Chi-square test and Kappa agreement. RESULTS: Of the 489 patients in BIOPSY, 299 were included in this study. Among them, 278 patients (93.0%) were eligible of TNF inhibitors when we applied the new initiation criteria with DAS28-ESR, and 244 patients (81.6%) were indicated for TNF inhibitors with DAS28-CRP. For the maintenance criteria, a low disease activity (DAS28<3.2) in 3 months after starting TNF inhibitors is too strict for achieving (33.6% with DAS28-ESR and 50.0% with DAS28-CRP). Instead, decreasing DAS28 by more than 1.2 is more reasonable as a tool for deciding early responsiveness of TNF inhibitors in RA patients (81.2% both with DAS28-ESR and DAS28-CRP). CONCLUSION: Our results show that the candidates for TNF inhibitors will be enormously changed according to a change in the reimbursement criteria. To define appropriate patients to receive TNF inhibitors, a further study with regard to the impact of changes in the reimbursement criteria on the outcomes of RA patients will be required.

SKI306X inhibition of glycosaminoglycan degradation in human cartilage involves down-regulation of cytokine-induced catabolic genes

BACKGROUND/AIMS: SKI306X, a mixed extract of three herbs, Clematis mandshurica (CM), Prunella vulgaris (PV), and Trichosanthes kirilowii (TK), is chondroprotective in animal models of osteoarthritis (OA). The objectives of this study were to investigate its effect on interleukin (IL)-1beta-induced degradation of glycosaminoglycan (GAG) and the basis of its action in human OA cartilage, as well as to screen for the presence of inhibitors of matrix metalloproteinase (MMP)-13 and a disintegrin and metalloprotease with thrombospondin motifs (ADAMTS)-4 in SKI306X and its component herbs, as well as in fractions from SKI306X. METHODS: Human OA chondrocytes and cartilage explants were obtained during total knee replacements and incubated with IL-1beta +/- oncostatin M with or without SKI306X or its component herb extracts. GAG degradation was assayed in cartilage explants using a commercial kit. Expression of genes involved in cartilage destruction was measured by real-time polymerase chain reaction using chondrocyte RNA. SKI306X was fractionated by preparative liquid chromatography to test for the presence of inhibitors of MMP-13 and ADAMTS-4. RESULTS: SKI306X and PV inhibited IL-1beta-induced GAG release from cartilage explants, and SKI306X, CM, PV, and TK inhibited IL-1beta-induced MMP gene expression. Unexpectedly, SKI306X greatly stimulated IL-1beta + oncostatin M-induced ADAMTS-4 gene expression, probably due to its TK component. Some fractions of SKI306X also inhibited ADAMTS-4 activity. CONCLUSIONS: SKI306X and its herbal components inhibit GAG degradation and catabolic gene expression in human OA chondrocytes and cartilage explants. SKI306X likely also contains one or more ADAMTS-4 inhibitor.