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

Objective To determine the risk factors for herpes zoster (HZ) in patients with rheumatic diseases in Korea. Methods We used the nationwide database of the Health Insurance Review & Assessment Service to analyse patients aged ≥20 years who had visited a hospital more than twice for rheumatic disease as a principal diagnosis from January 2009 to April 2013. HZ was identified using HZ-related Korean Standard Classification of Diseases 6 (KCD-6) codes and the prescription of antiviral agents. The relationship between demographics, comorbidities and medications and HZ risk was analysed by Cox proportional hazards models. Results HZ developed in 1869 patients. In Cox proportional hazards models, female sex but not age showed an increased adjusted hazard ratio (HR) for HZ. Comorbidities such as haematologic malignancies, hypertension, diabetes mellitus, and chronic lung and liver diseases led to an increased HR. HZ risk was higher in patients with SLE (HR: 4.29, 95% CI: 3.49, 5.27) and Behçet’s syndrome (BS, HR: 4.54; 95% CI: 3.66, 5.64) than with RA. The use of conventional DMARDs, immunosuppressants, TNF inhibitors, glucocorticoids and NSAIDs increased the HR. Infliximab and glucocorticoids (equivalent prednisolone dose >15 mg/day) produced the highest HZ risk (HR: 2.91, 95% CI: 1.72, 4.89; HR: 2.85, 95% CI: 2.15, 3.77, respectively). Conclusion Female sex, comorbidities and medications increased HZ risk in patients with rheumatic diseases and even young patients could develop HZ. Compared with RA, SLE and BS are stronger HZ risk factors. Patients with rheumatic diseases and these risk factors are potential target populations for HZ vaccination.

Patients with systemic rheumatic diseases (SRD) are vulnerable for coronavirus disease (COVID-19). The Korean College of Rheumatology recognized the urgent need to develop recommendations for rheumatologists and other physicians to manage patients with SRD during the COVID-19 pandemic. The working group was organized and was responsible for selecting key health questions, searching and reviewing the available literature, and formulating statements. The appropriateness of the statements was evaluated by voting panels using the modified Delphi method. Four general principles and thirteen individual recommendations were finalized through expert consensus based on the available evidence. The recommendations included preventive measures against COVID-19, medicinal treatment for stable or active SRD patients without COVID-19, medicinal treatment for SRD patients with COVID-19, and patient evaluation and monitoring. Medicinal treatments were categorized according to the status with respect to both COVID-19 and SRD. These recommendations should serve as a reference for individualized treatment for patients with SRD. As new evidence is emerging, an immediate update will be required. (J Rheum Dis 2020;27:218-232)

The use of magnetic resonance imaging (MRI) and positron emission tomography (PET) in rheumatology allows a better understanding of the pathophysiology of the disease as well as early diagnosis and appropriate evaluation of the disease status and treatment responses. Despite the limited availability because of the high cost, there is growing evidence for the advantages and clinical application of these modalities to various rheumatic diseases. This review discusses the basic mechanisms and clinical applications of MRI and PET in certain rheumatic diseases, including rheumatoid arthritis, axial spondyloarthritis, idiopathic inflammatory myopathies, large vessel vasculitis, central nervous system disease associated with rheumatic diseases, polymyalgia rheumatica, adult-onset Still’s disease, and immunoglobulin G4-related disease. (J Rheum Dis 2020;27:136-151)

Objectives This study aims to investigate the outcomes and risk factors associated with the progression of systolic pulmonary artery pressure (sPAP) in patients with systemic rheumatic diseases. Patients and methods A total of 532 patients (73 males, 459 females; median age 49 years; interquartile range (IQR), 36 to 62 years) registered with the Registry of Pulmonary Hypertension Associated with Rheumatic Diseases were included. Mortality curves were constructed using the Kaplan- Meier method and comparisons were performed using the log-rank test. A paired t-test was performed to evaluate the patients with markedly elevated sPAP between baseline and follow-up. Results The average follow-up duration was 31 months (IQR, 9 to 60 months). Of the patients, 196 had follow-up echocardiographs at least one year later. We defined the sPAP over 60 mmHg as markedly elevated. Patients in the increased sPAP above 60 mmHg at follow-up and persistently markedly elevated sPAP were associated with worse outcomes in all-cause mortality and pulmonary arterial hypertension-related mortality (p

Biological disease-modifying antirheumatic drugs (bDMARDs) are highly effective agents for the treatment of inflammatory arthritis; however, they also possess a potential risk for serious infection. Recently, with the rapid expansion of the bDMARDs market in Korea, reports of serious adverse events related to the agents have also increased, necessitating guidance for the use of bDMARDs. Current work entitled, “Expert Consensus for the Use of bDMARDs Drugs for Inflammatory Arthritis in Korea,” is the first to describe the appropriate use of bDMARDs in the management of inflammatory arthritis in Korea, with an aim to provide guidance for the local medical community to improve the quality of clinical care. Twelve consensus statements regarding the use of bDMARDs for the management of rheumatoid arthritis and ankylosing spondylitis were generated. In this review, we provide detailed guidance on bDMARDs use based on expert consensus, including who should prescribe, the role of education, indications for use, and monitoring strategies for safety. (J Rheum Dis 2020;27:4-21)

The coronavirus disease 2019 (COVID-19) pandemic has caused more than 100 million infections and 2 million deaths worldwide. In up to 20% of cases, COVID-19 infection can take a severe, life-threatening course. Therefore, preventive measures such as mask-wearing, hand hygiene, and social distancing are important. COVID-19 vaccines that use novel vaccine technology can prevent up to 95% of infections. However, the uncertainty regarding the efficacy and safety of vaccination in patients with autoimmune inflammatory rheumatic disease (AIIRD), who are immunocompromised due to underlying immune dysfunction and concomitant immunosuppressive treatment, warrants clear guidance. A task force of the Korean College of Rheumatology formulated a set of vaccination guidance based on the currently available data and expert consensus. The currently available COVID-19 vaccines are considered to be safe and effective. Every patient with AIIRD should receive one of the available COVID-19 vaccines unless contraindicated for medical reasons such as prior allergy/anaphylaxis to the COVID-19 vaccine or its components. Patients should continue immunosuppressive treatment for their underlying AIIRD, including biological and targeted synthetic disease-modifying anti-rheumatic drugs (b/tsDMARDs). Corticosteroids should be reduced to the lowest dose possible without aggravating the AIIRD. To improve the vaccine response, methotrexate can be withheld for 1-2 weeks after each vaccination, and the timing of rituximab and abatacept infusion should be adjusted if clinically acceptable. Rheumatologists should play a leading role in educating and vaccinating patients with AIIRD.

Background There is increasing interest in the quality of health care and considerable efforts are being made to improve it. Rheumatoid arthritis (RA) is a disease that can result in favorable outcomes when appropriate diagnosis and treatment are provided. However, several studies have shown that RA is often managed inappropriately. Therefore, the Korean College of Rheumatology aimed to develop quality indicators (QIs) to evaluate and improve the health care of patients with RA. Methods Preliminary QIs were derived based on the existing guidelines and QIs for RA. The final QIs were determined through two separate consensus meetings of experts. The consensus was achieved through a panel of experts who voted using the modified Delphi method. Results Fourteen final QIs were selected among 70 preliminary QIs. These included early referral to and regular follow-up with a rheumatologist, radiographs of the hands and feet, early initiation and maintenance of disease-modifying anti-rheumatic drug (DMARD) therapy, periodic assessment of disease activity, screening for drug safety and comorbidities, including viral hepatitis and tuberculosis before biologic DMARD therapy, periodic laboratory testing, supplementation with folic acid, assessment of the risk for cervical spine instability before general anesthesia, patient education, and specialized nurse. Conclusion These QIs can be used to assess and improve the quality of health care for patients with RA., Graphical Abstract

This study aimed to investigate the effect of short-term exposure to ambient particulate matter less than 10μm in diameter (PMThe data of emergency department (ED) cases with acute gout flare in Incheon city, Korea between January 1st 2008 and December 31st 2015 were collected from the National Health Insurance Service claims data. The levels of PMThe risk of daily ED visits for acute gout flares per interquartile range increment of the average daily PMOur time-series study demonstrated a modest, but significant effect of short-term exposure to PM

Background We purposed to evaluate the seasonality and associated factors of the incidence of gout attacks in Korea. Methods We prospectively enrolled patients with gout attacks who were treated at nine rheumatology clinics between January 2015 and July 2018 and followed them for 1-year. Demographic data, clinical and laboratory features, and meteorological data including seasonality were collected. Results Two hundred-five patients (men, 94.1%) were enrolled. The proportion of patients with initial gout attacks was 46.8% (n = 96). The median age, body mass index, attack duration, and serum uric acid level at enrollment were 50.0 years, 25.4, 5.0 days, and 7.4 mg/dL, respectively. Gout attacks were most common during spring (43.4%, P < 0.001) and in March (23.4%, P < 0.001). A similar pattern of seasonality was observed in the group with initial gout attacks. Alcohol was the most common provoking factor (39.0%), particularly during summer (50.0%). The median diurnal temperature change on the day of the attack was highest in the spring (9.8°C), followed by winter (9.3°C), fall (8.6°C), and summer (7.1°C) (P = 0.027). The median change in humidity between the 2 consecutive days (the day before and the day of the attack) was significantly different among the seasons (3.0%, spring; 0.3%, summer; −0.9%, fall; −1.2%, winter; P = 0.015). One hundred twenty-five (61%) patients completed 1-year follow-up (51% in the initial attack group). During the follow-up period, 64 gout flares developed (21 in the initial attack group). No significant seasonal variation in the follow-up flares was found. Conclusion In this prospective study, the most common season and month of gout attacks in Korea are spring and March, respectively. Alcohol is the most common provoking factor, particularly during summer. Diurnal temperature changes on the day of the attack and humidity changes from the day before the attack to the day of the attack are associated with gout attack in our cohort., Graphical Abstract

In dual-source CT, dual-energy (DE) performance is affected by various X-ray tube voltage combinations with and without tin filter (Sn). The purpose of this study was to assess the utility of the 80/150 Sn kV voltage combination in terms of image artefact and radiation dose for DECT gout protocol, compared with the conventional 80/140 kV. Seventy-four patients with suspected gout who underwent dual-source DECT examinations scanned at 80/140 kV (n = 37) and at 80/150 Sn kV (n = 37) were included. Patients’ age, sex, and serum uric acid levels were matched between the two groups. The types and incidence of image artefacts and radiation dose were evaluated. The 80/150 Sn kV group had significantly fewer patients with artefacts, compared to the 80/140 kV group [11 (30 %) of 37 vs 35 (94.6 %) of 37, p < 0.001]. Except for the motion artefact, the rest of the artefacts—skin, nail bed, submillimetre, motion, vascular, beam-hardening, clumpy artefact along tendon—were significantly less observed in the 80/150 Sn kV acquisitions. The dose-length product (DLP) and effective dose were significantly lower for the 80/150 Sn kV acquisitions compared with the 8s0/140 kV scans (DLP: 104.46 ± 10.66 mGy·cm vs 344.70 ± 56.39 mGy·cm, p < 0.001; effective dose: 1.04 ± 0.11 mSv vs 3.45 ± 0.56 mSv, p < 0.001). The 80/150 Sn kV voltage combination in dual-source DECT system could be used as one of the artefact reduction methods while reducing radiation dose for gout protocol when compared to the conventional 80/140 kV. • DECT has emerged as the leading modality for non-invasive diagnosis of gout. • Various X-ray tube voltage combinations are now feasible in dual-source DECT. • The 80/150 Sn kV acquisition could facilitate artefact reduction in gout protocol.

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

Background The prevalence and incidence of gout has risen over the past few decades and the socioeconomic costs of gout have been increasing accordingly, but it is unclear whether proper medical care is provided for patients with gout. Objectives This study aims to investigate the actual status and adequacy of diagnosis and management of gout patients. Methods The patients with gout who visited between November 2017 and February 2018 were consecutively enrolled. Data were collected using a pre-designed questionnaire and reviews of medical records. The collected data included diagnosis and management of gout before starting a steady treatment in our clinic, and disease status at first visit to our clinic. Results In total, 172 gout patients were enrolled. The average age of the patients was 55 (interquartile range (IQR): 45-66) years, and 94.2% were men. The average disease duration was 8 (IQR: 4-13) years. The average age of first gout symptoms was 45 (IQR: 36-53) years. The first symptom started in the feet for 93.4% of patients. The patients in which the first symptom region was around large joints were 35.1%, and 17.3% of patients developed first gout symptoms around multiple joints. Several patients (64%) visited the hospital directly after their first acute gout attack. The first physicians to examine gout patients were orthopedic surgeons (38.2%), emergency doctors (23.6%), and rheumatologist (16%). Upon initial medical examination, 67% of patients were clinically diagnosed or suspected with gout. Monosodium urate crystals in synovial fluid or tophi were confirmed in 10.5%. Furthermore, 31% of patients had a history of pharmacology urate lowering therapy (ULT) after acute gout attack, and 84.4% were indicated for pharmacologic ULT upon first visit to our clinic. Additionally, 47.6% of patients showed symptoms of chronic kidney disease, past urolithiasis, or tophi, and 52.4% suffered from ≥ 2 gout attacks/year. However, only 11.3% of patients were receiving continuous ULT before visiting our clinic. Conclusion Most patients were clinically diagnosed without appropriate tests for gout diagnosis, such as joint aspiration, and only a very small number of patients were receiving adequate pharmacologic ULT. The management of gout seems to be inadequate in many respects. References [1] Roddy E, Choi HK: Epidemiology of gout. Rheumatic diseases clinics of North America2014, 40(2):155-175. [2] Singh JA, Hodges JS, Toscano JP, Asch SM: Quality of care for gout in the US needs improvement. Arthritis and rheumatism2007, 57(5):822-829. [3] Young-Il S, Kyeong Min S, Young Ok J, In Je K, Kyung Lee K, Young Deok B, Hyun Ah K: Survey of Current Trends for Diagnosis and Treatment in Korean Gout Patients. J Rheum Dis2011, 18(3):187-192. [4] Doherty M, Bardin T, Pascual E: International survey on the diagnosis and management of gout. Annals of the rheumatic diseases2007, 66(12):1685-1686. Disclosure of Interests Mi Ryoung Seo Grant/research support from: I received KRW 15 million (approximately 1,300 USD) in research funding for this study from CHODANG Pharm., Ji Na Yeo: None declared, Hee Jung Ryu: None declared, Hyo-Jin Choi: None declared, Han Joo Baek: None declared

Author(s): Deodhar, Atul; Gensler, Lianne S; Sieper, Joachim; Clark, Michael; Calderon, Cesar; Wang, Yuhua; Zhou, Yiying; Leu, Jocelyn H; Campbell, Kim; Sweet, Kristen; Harrison, Diane D; Hsia, Elizabeth C; van der Heijde, Desiree | Abstract: ObjectiveTo evaluate the efficacy and safety of ustekinumab in 3 randomized, placebo-controlled studies in patients with axial spondyloarthritis (SpA). Studies 1 and 2 included patients with radiographic axial SpA (anti-tumor necrosis factor [anti-TNF]-naive patients and patients with inadequate response or intolerance to anti-TNF, respectively); study 3 patients had nonradiographic axial SpA.MethodsIn all 3 studies, patients were randomly assigned (1:1:1) to receive subcutaneous ustekinumab at 45 mg or 90 mg or placebo up to 24 weeks, after which placebo-treated patients were rerandomized to receive ustekinumab at 45 mg or 90 mg. The primary end point in studies 1 and 2 was the proportion of patients who met the Assessment of SpondyloArthritis international Society criteria for 40% improvement in disease activity (achieved an ASAS40 response). The primary end point in study 3 was the proportion of patients who achieved an ASAS20 response. Other disease activity and safety measures were also evaluated. A week 24 analysis of study 1 was preplanned to determine continuation of studies 2 and 3.ResultsFor study 1, the primary and major secondary end points were not met, and the study was discontinued. As a result, studies 2 and 3 were prematurely discontinued before they were fully enrolled. For all 3 studies, neither ustekinumab dose group demonstrated clinically meaningful improvement over placebo on key efficacy end points. The proportion of patients experiencing adverse events in the ustekinumab groups was consistent with that in previous studies.ConclusionIn these 3 placebo-controlled trials, efficacy of ustekinumab in the treatment of axial SpA was not demonstrated. The safety profile was consistent with that of studies in other indications.

Objectives This study aimed to investigate the effect of short-term exposure to ambient particulate matter less than 10 μm in diameter (PM10) on occurrence of acute gout flares in the general population and identify susceptible groups accordingly. Methods The data of emergency department (ED) cases with acute gout flare in Incheon city, Korea between January 1st 2008 and December 31st 2015 were collected from the National Health Insurance Service claims data. The levels of PM10 and meterological measurements were provided by the Ministry of Environment and the National Meterological Office, respectively. To estimate the risk of daily ED visits due to acute gout flare, these time-series data set were analyzed using generalized additive models with Poisson distribution, including daily average PM10 level, temperature, relative humidity, day of the week, national holiday, season, and date. Results The risk of daily ED visits for acute gout flares per interquartile range increment of the average daily PM10 levels significantly increased in the cumulative lag 0–7 model (relative risk, 1.018; 95% confidence interval, 1.008–1.027, P Conclusions Our time-series study demonstrated a modest, but significant effect of short-term exposure to PM10 on ED visits for acute gout flares. Ambient PM10 may be a newly identified environmental risk factor for acute gout flares.

Background:Gout shows a seasonal variation that widely differs among geographic areas, and we previously reported a seasonal effect on gout in Korea. However, we had no information regarding changes in diet and had only limited laboratory data because this was a retrospective study in patients receiving a urate-lowering therapy. Therefore, we designed this prospective study to elucidate the seasonality and associated factors of gout attacks in Korea.Objectives:To evaluate the seasonality and associated factors of the incidence of gout attacks in Korea.Methods:We prospectively enrolled patients with gout attacks who were treated at nine rheumatology clinics between January 2015 and July 2018 and followed them for 1-year. Demographic data, clinical and laboratory features, and meteorological data including seasonality were collected.Results:Two hundred-five patients (males, 94.1%) were enrolled. The proportion of patients with initial gout attacks was 46.8% (n = 96). The mean age, body mass index, attack duration, and serum uric acid level at enrollment were 50.5 years, 26.1, 10.2 days, and 7.3 mg/dL, respectively. Gout attacks were most common during spring (43.4%,P< 0.001) and in March (23.4 %,P< 0.001). A similar pattern of seasonality was observed in the group with initial gout attacks. Alcohol was the most common provoking factor (39.0%), particularly during summer (50.0%). The mean diurnal temperature change on the day of the attack was highest in the spring (10.3°C), followed by winter (9.1°C), summer (8.1°C), and fall (8.0°C) (P= 0.027). The mean change in humidity between the 2 consecutive days (the day before and the day of the attack) was significantly different among the seasons (3.4%, spring; 0.2%, summer; 0.4%, fall; -3.9%, winter;P= 0.015). One hundred twenty-five (61%) patients completed 1-year follow-up (51% in the initial attack group). During the follow-up period, 51 gout flares developed (18 in the initial attack group). No significant seasonal variation in the follow-up flares was found.Conclusion:In this prospective study, the most common season and month of gout attacks in Korea were spring and March, respectively. Alcohol was the most common provoking factor, particularly during summer. Diurnal temperature changes on the day of the attack and humidity changes from the day before the attack to the day of the attack were associated with gout attack in our cohort.References:[1]Choi HJ, Lee CH, Lee JH et al. Seasonality of gout in Korea: a multicenter study. J Korean Med Sci 2015;30:240-4.Disclosure of Interests: :None declared

Introduction Despite the availability of axial spondyloarthritis (SpA) recommendations proposed by various rheumatology societies, we considered that a region-specific guideline was of substantial added value to clinicians of the Asia-Pacific region, given the wide variations in predisposition to infections and other patient factors, local practice patterns, and access to treatment across countries. Materials and methods Systematic reviews were undertaken of English-language articles published between 2000 and 2016, identified from MEDLINE using PubMed, EMBASE and Cochrane databases. The strength of available evidence was graded using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach. Recommendations were developed through consensus using the Delphi technique. Results Fourteen axial SpA treatment recommendations were developed based on evidence summaries and consensus. The first 2 recommendations cover non-pharmacological approaches to management. Recommendations 3 to 5 describe the following: the use of non-steroidal anti-inflammatory drugs as first-line symptomatic treatment; the avoidance of long-term corticosteroid use; and the utility of conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) for peripheral or extra-articular manifestations. Recommendation 6 refers to the indications for biological DMARDs (bDMARDs). Recommendation 7 deals specifically with screening for infections endemic to Asia, prior to use of bDMARDs. Recommendations 7 to 13 cover the role of bDMARDs in the treatment of active axial SpA and include related issues such as continuing therapy and use in special populations. Recommendation 14 deals with the utility of surgical intervention in axial SpA. Conclusion These recommendations provide up-to-date guidance for treatment of axial SpA to help meet the needs of patients and clinicians in the Asia-Pacific region.

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

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

Background/Aims: This study was undertaken to perform a cross-cultural adaptation of the Behcet’s Disease Current Activity Form (BDCAF, version 2006) questionnaire to the Korean language and to evaluate its reliability and validity in a population of Korean patients with Behcet’s disease (BD). Methods: A cross-cultural study was conducted among patients with BD who attended our rheumatology clinic between November 2012 and March 2013. There were 11 males and 35 females in the group. The mean age of the participants was 48.5 years and the mean disease duration was 6.4 years. The first BDCAF ques tionnaire was completed on arrival and the second assessment was performed 20 minutes later by a different physician. The test-retest reliability was analyzed by computing κ statistics. Kappa scores of > 0.6 indicated a good agreement. To assess the validity, we compared the total BDCAF score with the patient’s/clinician’s perception of disease activity and the Korean version of the Behcet’s Disease Quality of Life (BDQOL). Results: For the test-retest reliability, good agreements were achieved on items such as headache, oral/genital ulceration, erythema, skin pustules, arthralgia, nausea/vomiting/abdominal pain, and diarrhea with altered/frank blood per rectum. Moderate agreement was observed for eye and nervous system involvement. We achieved a fair agreement for arthritis and major vessel involvement. Signifi cant correlations were obtained between the total BDCAF score with the BDQOL and the patient’s/clinician’s perception of disease activity (p < 0.05). Conclusions: The Korean version of the BDCAF is a reliable and valid instrument for measuring current disease activity in Korean BD patients.

Aim To describe the prevalence and characteristics of fibromyalgia (FM) in patients with underlying rheumatic disease, and to compare it by three different measures. Methods We studied 546 patients with chronic rheumatic diseases who attended our rheumatology clinic. If patients answered all of a screening questionnaire with yes, then we considered patients to be having widespread pain as assessed by the fibromyalgia impact questionnaire (FIQ), widespread pain index (WPI), and symptom severity (SS). A physician administered the tender point (TP) exam and clinician's judgment of FM. We collected demographics, clinical and laboratory features. Results One hundred and sixty-four (30.0%) patients among 546 cases had a further exam. The male-to-female count was 25 : 139. The mean age was 49.7 years, disease duration 3.7 years, TP counts 4.2, FIQ score 47.0 and WPI with SS score was 11.1. We classified 17 patients (10.4%) with concomitant FM with widespread pain by tender point exam, 56 patients (34.2%) by WPI with SS, and 36 patients (22.0%) by a clinician's judgment. A total of 70.6% (n = 12) of those classified as FM by 1990 American College of Rheumatology (ACR) criteria wee categorized as FM by clinician's judgment, while 33.3% by clinician's judgment were classified by 1990 ACR criteria. Conclusions We found a 10.4~34.2% prevalence of concomitant FM in the patients with chronic widespread pain. The 1990 ACR criteria were the most restrictive except for SLE. Although The 2010 ACR criteria had a wide spectrum, it can be used for FM diagnosis even in the patient with underlying rheumatic diseases.

The purpose of this study is to examine the patient-reported outcomes (PRO) after discontinuing nonsteroidal anti-inflammatory drugs (NSAIDs) and clinical factors associated with a favorable outcome in patients with rheumatoid arthritis (RA) in remission or with low-disease activity (LDA). A 16-week prospective open-label trial was conducted at eight rheumatology clinics in Korea. RA patients with 28-joint disease activity score based on erythrocyte sedimentation rate (DAS28-ESR)

We evaluated the COX-2 inhibitors, etoricoxib and celecoxib, in Korean patients with osteoarthritis (OA).This study included patients (≥ 40 years of age) with a clinical and radiographic diagnosis of knee OA. Patients were randomized to etoricoxib 30 mg (qd) or celecoxib 200 mg (qd) in a 12 week randomized, controlled, double-blind study. Prior NSAID users were to demonstrate a worsening of symptoms upon withdrawal of medication. Efficacy endpoints included the time-weighted average change from baseline in the WOMAC VA 3.0 Pain Subscale (100 mm Visual Analog Scale [VAS]; primary endpoint), the WOMAC VA 3.0 Physical Function Subscale (100 mm VAS), and Patient Global Assessment of Disease Status (PGAD) (100 mm VAS). The primary hypothesis was that etoricoxib 30 mg is non-inferior to celecoxib 200 mg as assessed by the primary endpoint (the non-inferiority margin was set at 10 mm VAS). Adverse events (AEs), laboratory parameters, and vital signs were monitored.There were 239 patients (89.5% female; mean age: 63.3 years) randomized to etoricoxib 30 mg (n = 120) and celecoxib 200 mg (n = 119). The differences (etoricoxib vs celecoxib) in least square (LS) mean change (95% CI) for WOMAC Pain, WOMAC Physical Function, and PGAD were -1.63 mm (-5.37, 2.10), -1.32 mm (-4.88, 2.23), and -1.09 mm (-5.48, 3.30), respectively. Drug-related clinical AEs occurred in 6.7% (etoricoxib) and 2.5% (celecoxib) of patients. This study was limited because it was not designed or powered to adequately capture and evaluate rare AEs associated with NSAID treatment.Etoricoxib 30 mg administered once daily in Korean patients with knee OA demonstrated non-inferior clinical efficacy to celecoxib 200 mg over 12 weeks of treatment as assessed by all primary and secondary outcomes. Etoricoxib 30 mg qd and celecoxib 200 mg qd were generally safe and well tolerated.NCT01554163.

The objectives of the study are to demonstrate the non-inferiority of PG201 (Layla®) 600 mg in comparison with celecoxib 200 mg for the treatment of symptomatic knee osteoarthritis (OA). In total, 309 patients were randomly assigned to receive either the test drug, PG201 600 mg (n = 154) or celecoxib 200 mg (n = 155). The primary efficacy variable was improvement in mean 100-mm pain VAS score from baseline to the final visit (week 8), and this value was compared between the 2 treatment groups. Secondary outcome variables included changes from baseline in the Western Ontario and McMaster Universities Arthritis Index (WOMAC) pain VAS score and subscale score, patient’s global assessment of disease status quality of life (short form-36) and responder index at weeks 4 and 8. For safety assessment, adverse events were recorded at each clinical visit. At weeks 8, the 100-mm pain VAS scores were significantly decreased in patients receiving both PG201 600 mg (p

Aim The aim of this study was to investigate the association between mean platelet volume (MPV) and clinical manifestations, disease activity or infection in patients with Behcet's disease (BD). Methods In total, 193 patients diagnosed with BD according to the international criteria for BD were enrolled. Demographic data, clinical manifestations and laboratory results were collected by medical interviews and reviewing medical records. Results The female : male ratio was 2 : 1 and the age of symptom onset was 32.2 ± 11.1 years. The age at diagnosis of BD was 44.7 ± 11.1 years and the follow-up duration was 4.7 ± 3.8 years. MPV at diagnosis were significantly lower than of age and sex-matched controls (8.2 ± 1.2 vs. 8.6 ± 1.2 fL, P < 0.0001). Lower MPV was not related to organ involvement except skin diseases. During follow-up, MPV was lower in BD flare than in stable BD (8.2 ± 1.4 vs. 9.1 ± 1.4 fL, P < 0.0001) in the same patients. MPVs were significantly higher in cases of accompanying infections than in those with both BD flare and stable BD (9.3 ± 1.4 vs. 8.1 ± 1.3 fL, P = 0.018 and 9.7 ± 1.4 vs. 8.8 ± 1.0 fL, P = 0.001, respectively). Conclusions MPV was significantly lower in patients with BD than controls. MPV declined in BD flare and increased in cases of infection in same patients. MPV may be useful as a marker of BD activity and its monitoring can be helpful for differentiating BD flare from infection in BD patients.

Our aim was to investigate the efficacy of monthly oral ibandronate in Korean women with rheumatoid arthritis and reduced bone mineral density (BMD) receiving long-term glucocorticoids.Patients (n = 167 women) were randomly assigned (1:1) to receive ibandronate 150 mg or placebo every 4 weeks. Patients had taken glucocorticoid (equivalent of daily prednisolone ≥5 mg) for 3 or more consecutive months before enrollment, and had a lumbar spine 1 to 4 (L1-L4) T-score of-1.0 and ≥ -2.5. Both groups were provided with daily calcium carbonate and cholecalciferol. The primary end point was the L1 to L4 BMD percent changes at 48 weeks compared with baseline.Baseline characteristics were comparable between the 2 groups. BMD percent changes in L1 to L4 at 48 weeks were significantly different between the ibandronate versus the placebo group (+3.7% [5.1%] vs -1.9% [4.4%], respectively; P0.0001). BMD percent changes at 48 weeks in femur neck and total hip also had similar results (P = 0.0073 and P = 0.0031, respectively). Decrease of serum type 1 collagen C-terminal telopeptide was significant at both 24 and 48 weeks in the ibandronate group. There was no incident of fragility fracture in both groups during the study period. Safety profiles, including adverse events, were comparable between the 2 groups.Monthly oral ibandronate for 48 weeks is well tolerated and effective in reducing bone mineral loss in women with rheumatoid arthritis on long-term glucocorticoid therapy. Longer follow-up studies are needed to investigate the benefit of ibandronate on fracture rate reduction in this subset of patients. ClinicalTrials.gov identifier: NCT01287533.

Background/Aims The clinical manifestations of Behcet disease (BD) have been reported to differ according to country, region, and race. Gender, onset age, and human leukocyte antigen (HLA)-B51 have also been known as the factors that influence the clinical features of BD. The aim of this study is to investigate the clinical phenotypes of Korean patients who visited the rheumatology clinic with BD with respect to gender, onset age, and HLA-B51. Methods Total 193 Korean patients (129 females and 64 males) fulfilling the international criteria for BD were retrospectively assessed. Results The mean age at disease onset and disease duration of the BD patients were 32.2 ± 11.1 and 14.2 ± 9.3 years, retrospectively. Females suffered more frequently from genital ulcers (90.7% vs. 75.0%, p < 0.01), peripheral arthritis (67.4% vs. 43.8%, p < 0.01), and inf lammatory low back pain (38.8% vs. 23.4%, p = 0.03) than males, while skin involvement was more frequent in males than in females (90.6% vs. 75.2%, p = 0.01). The patients with late onset of BD (> 40 years) suffered from neurologic involvement (15.9% vs. 4.2%, p = 0.007) more frequently than those with early onset of BD. The patients with HLA-B51 showed earlier onset of disease than without HLA-B51 (28.3 ± 11.4 years vs. 33.8±11.6 years, p = 0.02) and the neurologic and gastrointestinal involvements were more frequent in the patients without HLA-B51 than with HLA-B51 (17.2% vs. 2.5%, p = 0.02 and 20.7% vs. 2.5%, p = 0.01, respectively). Conclusions The clinical phenotypes in Korean patients with BD may be influenced by gender, onset age and HLA-B51.

Objectives To identify non-major histocompatibility complex susceptible genes that might contribute to Behcet9s disease (BD). Methods We performed a genome-wide association study using DNA samples from a Korean population consisting of 379 BD patients and 800 controls. A replication study was performed in a Japanese population (363 BD patients and 272 controls). To evaluate the functional implication of the target single nucleotide polymorphisms (SNP), gene expression levels in peripheral T cells, allele-specific modulation of promoter activity and biological effect of mRNA knockdown were investigated. Results We found a novel association of BD to the GIMAP locus, mapped to chromosome 7q36.1 (rs1608157, p=6.01×10 −8 in a minor allele dominant model; rs11769828, allele based p=1.60×10 −6 ). A fine mapping study identified an association with four additional SNP: rs1522596 (OR=1.45, p=7.70×10 −6 ) in GIMAP4 ; rs10266069 (OR=1.32, p=2.67×10 −4 ) and rs10256482 (OR=1.27, p=5.27×10 −4 ) in GIMAP2 ; and rs2286900 (OR=1.61, p=3.53×10 −5 ) in GIMAP1 areas. Replication study using DNA samples from the Japanese population validated the significant association between BD and the GIMAP locus. The GIMAP4 promoter construct plasmid with the minor allele of rs1608157 displayed significantly lower activity than one with the major allele. Moreover, CD4 T cells from BD patients showed a lower level of GIMAP4 mRNA, and GIMAP4 knockdown was protective against Fas-mediated apoptosis. Conclusions These results suggest that a GIMAP cluster is a novel susceptibility locus for BD, which is involved in T-cell survival, and T-cell aberration can contribute to the development of BD.

Chronic obstructive pulmonary disease (COPD) is one of the causes of cor pulmonale. Cor pulmonale patients with pulmonary hypertension have a significant lower survival rate than patients without. However, there is no conclusive treatment options in cor pulmonale and pulmonary hypertension associated with COPD until now. We report a patient with cor pulmonale and pulmonary hypertension associated with severe form of COPD and tuberculous destroyed lung who achieved marked clinical, functional and echocardiographic hemodynamic improvements with inhaled iloprost for six months.

Objectives: Interleukin (IL)4+CD8+ regulatory T cells (Treg) obtained from peripheral blood mononuclear cells (PBMCs) from patients with ankylosing spondylitis (AS) by coculture with autologous dendritic cells (DC) have been previously described. In the present work, the proportions of IL4+CD8+ T cells in PB from patients with AS and controls are examined; in addition the conditions required for the generation of IL4+CD8+ Treg cells and their frequency in T cell lines from patients with AS and controls are investigated. Methods: CD8+ T cells were either stimulated non-specifically ex vivo and intracellular cytokines examined, or cocultured with DC and other stimuli, for 2 weeks. The resulting lines were analysed for cytokine expression. Clones derived from these lines were tested for regulatory function. Results: PBMCs from patients with AS and from human leukocyte antigen (HLA)-B27+ healthy controls contained a higher frequency of IL4+CD8+ T cells than those from HLA-B27− controls. Likewise, CD8+ T cell lines obtained by coculture with DC contained a higher ratio of IL4+ to interferon (IFN)γ+ cells when obtained from patients with AS or HLA-B27+ controls. T cell clones obtained from these lines showed regulatory activity. Outgrowth of IL4+ CD8+ T cells required contact with DC, but not maturation with lipopolysaccharide (LPS); allogeneic DC were also effective. Coculture with lymphoblastoid cells, or anti-CD3/CD28 microbeads, produced only expansion of IFNγ-producing CD8+ T cells. Conclusions: The higher proportion of CD8+ cells which can produce IL4 in PB and in expanded CD8+ T cell lines suggests an altered pattern of CD8+ T cell differentiation in AS and in HLA-B27+ healthy individuals. This predisposition to generate IL4+CD8+ T cells may play a role in pathogenesis of spondyloarthritis.

Background: SKI306X, which consists of biologically active ingredients from Clematis mandsburica, Tricbosantbes kirilowii, and Prunella vulgaris, was developed and tested in preclinical trials in Korea. Those studies found that SKI306X was associated with an anti-inflammatory and analgesic effect, and that it can delay the destruction of cartilage in rheumatoid arthritis (RA). Objective: The aim of this study was to compare the pain relief and tolerability of SKI306X and celecoxib in patients with RA. Methods: This study was a 6-week, multicenter, randomized, double-blind, double-dummy, Phase III, noninferiority clinical trial. Eligible patients were aged 18 to 80 years, had a history of RA with a disease duration of ≥3 months, and were functional American College of Rheumatology (ACR) class I, II, or III before entry. After a washout period of 2 weeks, patients were randomized to SKI306X 200 mg TID or celecoxib 200 mg BID for 6 weeks. The primary end point was a change in patient assessment of pain intensity using a visual analog scale (VAS). The secondary end points were a 20% improvement in response rate as defined by the ACR (ACR20) and the frequency of rescue medication use. Results after 3 and 6 weeks of treatment were compared with baseline and between treatment groups, and all patients were assessed for adverse events (AEs), clinical laboratory data, and vital signs. AEs were identified based on spontaneous reports by patients during interviews conducted by the investigators and the study coordinator. Results: Two hundred twenty-two Korean patients from 7 medical centers were assessed and 183 were enrolled and randomized to 1 of 2 treatment groups. Ninety-one patients (10 male, 81 female; mean [SD] age, 52.13 [12.64] years; mean [SD] duration of RA, 9.08 [10.23] years; no. [%] of ACR class I, II, and III, 13 [14.29], 44 [48.35] and 34 [37.36] patients, respectively) received SKI306X 200 mg TID and 92 patients (10 male, 82 female; mean [SD] age, 51.78 [10.94] years; mean [SD] duration of RA, 8.78 [7.78] years; no. [%] of ACR class I, II, and III, 14 [15.22], 44 [47.83], and 34 [36.96] patients, respectively) received celecoxib 200 mg BID. An analysis of the change in reported pain intensity as determined by VAS (mm) score between baseline and week 3 (mean [SD], 13.64 [16.62] vs 14.45 [15.89]), and between baseline and week 6 (18.4 [20.8] vs 17.9 [19.1], respectively) suggested that SKI306X was not inferior to celecoxib. The number of patients who achieved ACR20 response rate was not significantly different between the SKI306X group and the celecoxib group at week 3 (16/87 [18.4%] vs 24/87 [27.6%], respectively) and at week 6 (29/87 [33.3%] vs 29/87 [33.3%]). The frequency of rescue medication use was not significantly different between the SKI306X group and celecoxib group at week 3 (54/87 [62.1%] vs 47/87 [54.0%], respectively) or week 6 (57/87 [65.5%] vs 49/87 [56.3%]). Drug-related AEs were reported by 27 (29.7%) patients in the SKI306X group and 22 (23.9%) patients in the celecoxib group. The most frequent drug-related AEs were epigastric pain (9/91 [9.9%]) in the SKI306X group and glutamyltranferase elevation (4/92 [4.3%]) in the celecoxib group. No significant between-group differences were observed in the prevalence of drug-related clinical- or laboratory-determined AEs. Conclusion: The results of this study suggest that SKI306X was generally well tolerated and not inferior to celecoxib in regard to pain relief in these Korean patients with RA.