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Objective Anti-TNF biologics have been widely used to ameliorate disease activity in patients with RA. However, a large fraction of patients show a poor response to these agents. Moreover, no clinically applicable predictive biomarkers have been established. This study aimed to identify response-associated biomarkers using longitudinal transcriptomic data in two independent RA cohorts. Methods RNA sequencing data from peripheral blood cell samples of Korean and Caucasian RA cohorts before and after initial treatment with anti-TNF biologics were analysed to assess treatment-induced expression changes that differed between highly reliable excellent responders and null responders. Weighted correlation network, immune cell composition, and key driver analyses were performed to understand response-associated transcriptomic networks and cell types and their correlation with disease activity indices. Results In total, 305 response-associated genes showed significantly different treatment-induced expression changes between excellent and null responders. Co-expression network construction and subsequent key driver analysis revealed that 41 response-associated genes played a crucial role as key drivers of transcriptomic alteration in four response-associated networks involved in various immune pathways: type I IFN signalling, myeloid leucocyte activation, B cell activation, and NK cell/lymphocyte–mediated cytotoxicity. Transcriptomic response scores that we developed to estimate the individual-level degree of expression changes in the response-associated key driver genes were significantly correlated with the changes in clinical indices in independent patients with moderate or ambiguous response outcomes. Conclusion This study provides response-specific treatment-induced transcriptomic signatures by comparing the transcriptomic landscape between patients with excellent and null responses to anti-TNF drugs at both gene and network levels. [ABSTRACT FROM AUTHOR]

We aimed to determine the risk of herpes zoster (HZ) in Korean rheumatoid arthritis (RA) patients on tofacitinib compared with tumor necrosis factor inhibitor (TNFi) treatment. From the prospective cohorts of RA patients who started tofacitinib or TNFi in an academic referral hospital in Korea, patients who started tofacitinib between March 2017 and May 2021 and those who started TNFi between July 2011 and May 2021 were included. Baseline characteristics of tofacitinib and TNFi users were balanced through inverse probability of treatment weighting (IPTW) using the propensity score including age, disease activity of RA and medication use. The incidence rate of HZ in each group and incidence rate ratio (IRR) were calculated. A total of 912 patients were included: 200 tofacitinib and 712 TNFi users. There were 20 cases of HZ among tofacitinib users and 36 among TNFi users during observation period of 331.4 person-years (PYs) and 1950.7 PYs, respectively. In IPTW analysis with a balanced sample, IRR of HZ was 8.33 (95% confidence interval 3.05–22.76). Tofacitinib use increased the risk of HZ compared with TNFi in Korean patients with RA, but the rate of serious HZ or permanent discontinuation of tofacitinib due to HZ event was low. [ABSTRACT FROM AUTHOR]

Objective: Deciding which drug to choose for targeted therapy is an important step in sequential treatment for rheumatoid arthritis (RA). This study aimed to identify factors for selecting Janus kinase inhibitors (JAKis) rather than biologic disease-modifying antirheumatic drugs (bDMARDs) in patients with RA in real-world practice. Methods: We selected RA patients starting JAKis or bDMARDs from single-center prospective cohorts in Korea. Patients were divided into JAKi, tumor necrosis factor (TNF) inhibitor, and non-TNF inhibitor groups. We performed multinomial logistic regression analyses to identify factors associated with selecting JAKis. Results: 145, 205, and 89 patients were included in the JAKi, TNF inhibitor, and non-TNF inhibitor groups. In multinomial regression analysis, the JAKi group was older than the TNF inhibitor group (OR 1.03, 95% confidence interval [CI] 1.01–1.05) but younger than the non-TNF inhibitor group (OR 0.97, CI 0.95–1.00). The JAKi group was less likely to have chronic pulmonary diseases compared with the TNF inhibitor group (OR 0.07, CI 0.01–0.56) or the non-TNF inhibitor group (OR 0.06, CI 0.01–0.50). Higher disease activity assessed by physician (OR 1.80, CI 1.51–2.38) and previous tacrolimus use (OR 2.05, CI 1.20–3.51) were factors suggesting selection of JAKis than TNF inhibitors. Conclusion: Age, pulmonary comorbidities, previous tacrolimus use, and high disease activity assessed by physician were factors influencing the selection of JAKis for RA patients in Korea. [ABSTRACT FROM AUTHOR]

Objectives: We conducted the cross‐cultural adaptation and validation of the Leeds Satisfaction Questionnaire (LSQ) for patients with rheumatoid arthritis (RA) in Korea. Methods: The adaptation of the LSQ from English into Korean was based on guidelines for cross‐cultural adaptation for self‐report measures. Patients with RA were recruited from an outpatient clinic of a university hospital in South Korea. Validation of the Korean‐LSQ with Rasch models was carried out using WINSTEPS. Model fit was determined by Infit and Outfit statistics (≥0.50 and ≤1.50), including the separation index (≥2.00) and reliability index (≥0.80). Results: The data set comprised 125 patients (82.4% female), with median (interquartile range) age 49.0 (37‐57) years, and disease duration of 2.5 (1.2‐3.8) years. The total and subscale scores of the Korean‐LSQ demonstrated excellent or good test‐retest reliability (0.88 for total, 0.71‐0.82 for subscales), and items in the scale also revealed a high internal consistency (α = 0.93). The six subscales of the Korean‐LSQ were found to have a good fit to the Rasch model and good reliability (Person separation index = 2.63 and reliability index = 0.87; item separation index = 37.03 and reliability index >0.99). In addition, the unidimensionality of the scale was confirmed by the principal component analysis based on the Rasch residuals. Conclusion: Fit to the Rasch model confirmed that the construct validity, reliability, and unidimensionality of the LSQ were preserved following the adaptation into Korean. The Korean‐LSQ is a valid and reliable tool for measuring satisfaction with care in Korean patients with RA. [ABSTRACT FROM AUTHOR]

Objective: To compare the effectiveness of azathioprine (AZA) and cyclosporine (CsA) as initial treatments for patients with idiopathic inflammatory myopathies (IIM). Methods: A retrospective cohort study was conducted using information from the National Health Insurance Service database of Republic of Korea. Patients with IIM who had started AZA or CsA as initial treatment between January 2007 and December 2011 were selected for the study. They were followed from the day of treatment initiation to the occurrence of study outcomes or the end of the study until December 2016. Effectiveness outcomes, defined as switching the drug or adding immunosuppressants, and discontinuation of corticosteroids, were compared between the two groups. The Cox proportional-hazards model was used to calculate the adjusted relative risk (aRR) with 95% confidence interval (CI) between the AZA and CsA groups. Results: A total of 376 patients with incident IIM who used AZA (n = 288) or CsA (n = 88) were identified. The aRR of switching the drug or adding immunosuppressants (1.45 [95% CI 0.99–2.11]) was not significantly different between the CsA and AZA groups. Among patients who were treated with corticosteroids at baseline, the rate of discontinuation of corticosteroids was not different between the two groups (1.69 [95% CI 0.82–3.47]). Conclusions: The effectiveness of AZA and CsA as initial treatments for the management of IIM was comparable. [ABSTRACT FROM AUTHOR]

Background: To identify factors for starting biosimilar TNF inhibitors (TNFI) in patients with rheumatic diseases. Methods and finding: Using a national claims database, we identified patients with rheumatoid arthritis (RA) or ankylosing spondylitis (AS) who had used TNFIs since they were approved in Korea in 2004. We assessed changes in the proportion of each form of TNFI used between 2004 and 2017. We then selected patients starting on TNFIs between 2013 and 2017 to identify factors for starting biosimilars. In RA (n = 4,216), biosimilars were more likely to be initiated in clinics [odds ratio (OR) 2.54] and in the metropolitan area (OR, 2.02), but were less likely to be initiated in general hospitals (OR 0.40) or orthopedics (OR 0.44). In AS (n = 2,338), biosimilars were common at the hospital level (OR 2.20) and tended to increase over the years (OR 1.16), but were initiated less in orthopedics (OR 0.07). In addition, RA patients were more likely to initiate biosimilars in combination with methotrexate (OR 1.37), but biosimilars were not initiated frequently by patients with higher comorbidity scores (OR 0.97) or receiving glucocorticoids (OR 0.67). The patient factors favoring biosimilar in AS use were not clear. Conclusions: In Korea, the proportion of biosimilar TNFIs has increased. Type of institution and physician specialty are more important than patient factors in affecting biosimilar use. In RA, biosimilar TNFIs tend to be initiated in combination with MTX, and are less likely to be initiated in patients taking glucocorticoids or in those with high comorbidities. [ABSTRACT FROM AUTHOR]

Aim: To compare medication prescriptions for patients with knee osteoarthritis (KOA) in the real world in Korea and Japan. Methods: This retrospective and descriptive population‐based study was conducted using claims data provided by Health Insurance Review and Assessment in Korea and JMDC Inc in Japan. We defined individuals as KOA patients if they had an International Classification of Diseases 10 (ICD10) code for gonarthrosis (M17) and were ≥50 years old in 2012. Korean and Japanese patients were matched for age and sex using frequency matching. Patients were observed for 1 year from the first month of the ICD10 code M17 in 2012. We described baseline characteristics including prevalence of comorbidities, and use of medication for KOA during the observational period. Results: The median age was 59 and the percentage of women was 61.4 in both countries (N = 1 133 138 in Korea, N = 10 498 in Japan). The prevalence of nonsteroidal anti‐inflammatory drug (NSAID) usage in Japan (74.7%) was significantly higher than that in Korea (59.0%). Analgesics such as acetaminophen and symptomatic slow‐acting drugs for OA (SYSADOA) were significantly more frequently used in Korea (25.8%) than in Japan (9.4%). Intra‐articular injection (IAI) of corticosteroids or hyaluronic acid was performed more frequently in Japanese patients (57.3%) than Korean patients (30.5%). Conclusions: Medication patterns for KOA in Korea and Japan are described for the first time. Use of NSAIDs and IAI were more common in Japan, while other pain killers and SYSADOA were more commonly prescribed in Korea. [ABSTRACT FROM AUTHOR]

Abstract: Aim: Osteonecrosis (ON), also known as avascular necrosis, is an important cause of physical disability in rheumatic disease. When this condition affects multiple structures, disability is increased. The purpose of this study was to describe the clinical characteristics of Korean patients with multifocal ON associated with rheumatic disease and to compare them with those of previously reported cases. Methods: We reviewed the clinical characteristics of eight Korean patients with multifocal ON, defined by the involvement of three or more anatomic sites, associated with rheumatic disease in a single referral academic hospital, and compared them with those of 19 similar cases previously reported in the literature. Results: All eight patients were female, with median age of 26 years. All had underlying systemic lupus erythematosus (SLE) and had been using corticosteroids. The most common site affected by ON was the knee joint. However, in contrast to our patients, the previous reported cases had other rheumatic diseases such as myositis, scleroderma and antiphospholipid syndrome. In comparison between Korean multifocal ON patients with SLE and those of previous reports, shoulder joint involvement was higher in previous reports. Common features in patients from both groups were knee joint involvement and prevalent use of corticosteroids. Conclusion: Our findings indicate that multifocal ON is common in young SLE patients who have been using corticosteroids and the most commonly involved site is the knee. [ABSTRACT FROM AUTHOR]

To identify the factors associated with perceived unmet medical needs in human immunodeficiency virus (HIV)-infected adults, we analyzed the results from a series of city-wide cross-sectional surveys of HIV-infected adults living in Seoul, Korea. Multivariate logistic regression analysis was used to identify factors related to unmet medical needs. Among the 775 subjects included in the study, 15.4% had perceived unmet medical needs. Significant factors included age group (35-49 years; adjusted odds ratio [aOR], 1.80; 95% confidence interval [CI], 1.06-3.06), lower monthly income (aOR, 3.75 for the <$900/mo group and 2.44 for the $900-$1800/mo group; 95% CI, 1.68-8.35 and 1.18-5.04, respectively), beneficiaries of the National Medical Aid Program (aOR, 1.78; 95% CI, 1.01-3.17), recent CD4 cell counts <500/μL (aOR, 1.53; 95% CI, 1.01-2.33). Taken together, these data reveal strong associations of middle age and low socioeconomic status with perceived unmet medical needs among HIV-infected adults. [ABSTRACT FROM AUTHOR]

Many studies have investigated risk factors for suicidal ideation and suicide attempt; however, most have failed to show differences in risk factors between suicidal ideation and suicide attempt among the human immunodeficiency virus (HIV)-infected population. This study was designed to identify differences in risk factors between suicidal ideation and suicide attempts among HIV-infected adults in Seoul. A face-to-face survey of 457 HIV-infected adults was conducted by the Seoul Metropolitan Government in 2013. Multivariate logistic regression analysis was used to identify factors associated with suicidal ideation and suicide attempt. Among 422 participants, 44% had suicidal ideation, and 11% had suicide attempts. The independent risk factors for suicidal ideation were young and middle age, living with someone, history of AIDS-defining opportunistic disease, history of treatment for depression, lower social support, and psychological status. Beneficiaries of National Medical Aid, economic barriers to treatment, history of treatment for depression, and lower psychological status were independently associated with suicide attempts. Patients with HIV in Korea were treated without cost in some centers. Thus, experiencing an economic barrier to treatment might be due in part to ignorance of HIV care policies. Our findings indicate that suicide attempts are associated with socioeconomic factors and information inequality regarding medical care. In conclusion, suicidal ideation closely associated with the psychosocial factors, whereas suicide attempt demonstrates a stronger association with socioeconomic factors. Suicide prevention measures should be implemented to provide information to help HIV-infected patients. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to investigate the prevalence of osteoporosis in rheumatoid arthritis (RA) patients and to analyze the risk factors in these patients using the KORean Observational study Network for Arthritis (KORONA) database.Methods: Among the RA patients in the KORONA who were recruited between July 2009 and December 2011, postmenopausal women with bone mineral density (BMD) results within one year from the time of KORONA enrollment were included in this study. The baseline characteristics of patients in three groups, defined by BMD results, were compared. The BMD measurement rates and prevalence of osteoporosis in the study patients were calculated in accordance with age and gender subgroups. Multivariable logistic regression analysis was used to explore the association between osteoporosis and demographics and disease-related risk factors.Results: Of 1322 postmenopausal woman patients with RA in whom BMD was measured within one year of study enrollment, 619 patients (46.8 %) were in the osteoporosis group (T-score ≤ -2.5 SD). RA patients with osteoporosis had a higher frequency of previous fractures than those in other groups, especially fractures of the femur (p = 0.004) and wrist (p = 0.042). Advanced age (≥70 years; OR = 2.28, 95 % CI: 1.40-3.58), lower body mass index (<25; OR = 2.14, 95 % CI:1.52-3.02), longer disease duration (≥10 years; OR = 1.46, 95 % CI: 1.07-2.00), higher cumulative glucocorticoid dose (OR = 1.03, 95 % CI: 1.01-1.05), and higher Health Assessment Questionnaire score (OR = 1.37, 95 % CI:1.11-1.69) were independent risk factors for osteoporosis.Conclusion: A large percentage (90.8 %) of RA patients enrolled in the KORONA cohort had osteoporosis and osteopenia. Nevertheless, BMD measurement rates in this population remained low, despite high risk groups of fractures. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

This study aimed to develop an identification algorithm for validating the International Classification of Diseases-Tenth diagnostic codes for rheumatoid arthritis (RA) in the Korean National Health Insurance (NHI) claims database. An individual copayment beneficiaries program for rare and intractable diseases, including seropositive RA (M05), began in South Korea in July 2009. Patients registered in this system pay only 10 % of their total medical costs, but registration requires an official report from a doctor documenting that the patient fulfills the 1987 ACR criteria. We regarded patients registered in this system as gold standard RA and examined the validity of several algorithms to define RA diagnosis using diagnostic codes and prescription data. We constructed nine algorithms using two highly specific prescriptions (positive predictive value >90 % and specificity >90 %) and one prescription with high sensitivity (>80 %) and accuracy (>75 %). A total of 59,823 RA patients were included in this validation study. Among them, 50,082 (83.7 %) were registered in the individual copayment beneficiaries program and considered true RA. We tested nine algorithms that incorporated two specific regimens [biologics and leflunomide alone, methotrexate plus leflunomide, or more than 3 disease-modifying anti-rheumatic drugs (DMARDs)] and one sensitive drug (any non-steroidal anti-inflammatory drug (NSAID), any DMARD, or any NSAID plus any DMARD). The algorithm that included biologics, more than 3 DMARDs, and any DMARD yielded the highest accuracy (91.4 %). Patients with RA diagnostic codes with prescription of biologics or any DMARD can be considered as accurate cases of RA in Korean NHI claims database. [ABSTRACT FROM AUTHOR]

Several studies of rheumatoid arthritis (RA) incidence and prevalence indicate that occurrence of the disease varies significantly among different populations. We aimed to estimate the prevalence and incidence of RA in South Korea. We used Korean National Health Insurance (NHI) claims data to estimate the prevalence of RA in 2007-2009 and the incidence of RA in 2008. On the basis of our previous validation study, the presence of RA was defined by the diagnostic code for RA with biologic or non-biologic disease-modifying anti-rheumatic drugs in the same claim in each year. To estimate the incidence of RA, we identified cases of RA in 2008 and set the 12-month period prior to 2008 as a disease-free period. Among the incident case of 2008, only patients who continued treatment in 2009 were defined as true incident case of RA in 2008. The corresponding prevalence estimates were 0.26 % (95 % CI 0.25-0.27) in 2006, 0.27 % (95 % CI 0.26-0.28) in 2007, and 0.27 % (95 % CI 0.26-0.28) in 2008. The incidence of RA in 2008 was estimated at 42/100,000 (95 % CI 29.3-54.7) in the general population of South Korea. Data gathered nationwide through the NHI yielded estimates of RA prevalence and incidence in South Korea. This study is the first report of nationwide prevalence and incidence of South Korea and those are comparable to values for other countries in Asia. [ABSTRACT FROM AUTHOR]

The aim of the study was to identify factors influencing the health-related quality of life (HR-QOL) for Korean RA patients and factors associated with each dimension of the EQ-5D. Two hundred and twenty-five RA patients were recruited from one University Hospital in Seoul, South Korea. Their clinical and socio-demographic data were widely collected by means of interviews, self-administered questionnaires, and clinical examinations. Multiple logistic regression analyses were performed to determine the factors influencing QOL and factors associated with each dimension of the EQ-5D. The mean EQ-5D utility observed for Korean RA patients was 0.60 (−0.29 to 1.0). Functional disability measured with Health Assessment Questionnaire (OR = 10.0, CI 2.8-34.5), disease activity score (DAS) 28 (OR = 2.6, CI 1.4-4.9), and pain VAS (OR = 2.2, CI 1.2-4.1) was three main factors influencing on QOL of RA patients. Although the functional disability consistently showed significant associations with all dimensions, various factors were associated with the each five specific dimension of EQ-5D. Pain (OR = 2.5, CI 1.4-4.6), history of hospitalization (OR = 2.1, CI 1.0-4.3), and men (OR = 2.6, CI 1.0-6.8) were associated with lower QOL in mobility. Use of alternative medicine (OR = 2.0, CI 1.1-3.7) and disease activity (OR = 3.1, CI 1.7-5.7) were associated with lower self-care QOL. For the patients with discomfort in usual activity, pain (OR = 4.7, CI 2.4-9.2) and the presence of anemia (OR = 2.3, CI 1.2-4.5) were major influencing factors. Higher disease activity (OR = 4.5, CI 1.0-21.2) and pain (OR = 3.3, CI 1.9-5.8) were associated with the pain/discomfort dimension of EQ-5D, and the pain (OR = 3.3, CI 1.9-5.8) was an independent associating factor of anxiety/depression. The strongest determinants of lower QOL in Korean RA patients were functional disability, higher disease activity, and subjective pain. However, various factors are influencing on the QOL for RA patients according to aspects of QOL. It suggested that clinicians should pay more attention to other factors of RA patients as well as clinical remission to improve their QOL. [ABSTRACT FROM AUTHOR]