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Objective: The objective of this study was to assess the effectiveness of tofacitinib vs TNF inhibitors (TNFis) in Korean patients with RA., Methods: The study used data from a single academic referral hospital's registries of biologic DMARDs (bDMARDs) and tofacitinib and examined remission rates based on the DAS28-ESR after 12 months. Multivariable logistic regression analysis was used to estimate the odds ratio (OR) for achieving remission with tofacitinib compared with TNFi, adjusting for potential confounders., Results: This analysis included 665 patients (200 on tofacitinib and 455 on TNFis) who were followed up for at least 12 months. Of these, 96 patients in the tofacitinib group (48.0%) and 409 patients in the TNFi group (89.9%) were treatment-naïve to bDMARDs. Intention-to-treat analysis revealed no significant difference in the remission rates between the two groups (18.0% vs 19.6%, P = 0.640). Multivariable analysis demonstrated comparable remission rates with tofacitinib and TNFi (OR 1.204, 95% CI 0.720-2.013). In the subpopulation naïve to Janus kinase inhibitors (JAKis) and bDMARDs, tofacitinib showed better remission rates than TNFis (OR 1.867, 95% CI 1.033-3.377). Tofacitinib had more adverse events but similar rates of serious adverse events to TNFis., Conclusion: In real-world settings, there was no significant difference in remission rates at 12 months between the tofacitinib and TNFi groups. In terms of safety, tofacitinib exhibited a higher incidence of adverse events compared with TNFis, while the occurrence of serious adverse events was comparable between the groups., Trial Registration: ClinicalTrials.gov, https://clinicaltrials.gov, NCT02602704., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objectives: To investigate the trends in immunomodulator use and pregnancy outcomes among pregnant women with systemic lupus erythematosus (SLE), a condition requiring medication to maintain disease activity., Methods: This descriptive study used data from the National Health Information Database in Korea from 2002 to 2018. We included 5,044 pregnancies initiated between 2005 and 2017 in 3,120 SLE patients. Annual trends in SLE therapy, drug utilisation patterns during the preconception and pregnancy periods, and pregnancy outcomes were analysed., Results: Pregnancy compatible immunosuppressant (PC-IS) and hydroxychloroquine use during the first trimester were 10.7% and 41.4%, respectively. Most SLE medications exhibited a decline in usage from the preconception period to the first trimester. A prescription rate of 0.9% for pregnancy incompatible immunosuppressants (PIC-IS) was observed during the first trimester, and the incidence of live births, stillbirths, and abortions remained consistent from 2005 to 2017., Conclusions: Insufficient usage of hydroxychloroquine and PC-IS, along with a reduction in PIC-IS usage primarily during early pregnancy rather than before conception, highlights the unmet need for preconceptional family planning with appropriate medication management strategies in SLE pregnancies., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objectives: This study aimed to investigate the association between the genetic burden of systemic lupus erythematosus (SLE) and the loss of tolerance to self-nuclear antigens in the preclinical stage., Methods: We analysed genetic data from 349 Korean individuals who tested positive for autoantibodies in the preclinical stage, along with 33,596 healthy controls and 2057 patients with SLE. Genome-wide and pathway-specific polygenic risk scores (PRSs) of SLE were calculated based on 180 known non-human leukocyte antigen (non-HLA) SLE loci, HLA-DRB1 classical alleles, and predefined immune-related pathways to subsequently correlate with clinical phenotypes, particularly the presence of antinuclear antibodies (ANAs) at various titre thresholds., Results: Individuals with preclinical autoimmune conditions exhibited significantly higher SLE PRSs than healthy controls (P = 2.99 × 10 -5 ), with a significantly upward trend between ANA titres and PRS (P = 1.12 × 10 -3 ). Stratification analysis revealed that preclinical-stage individuals with PRSs exceeding the means of age- and sex-matched PRSs among patients with SLE were at a significantly higher risk of ANA development (odds ratio = 2.25; P = 8.12 × 10 -3 at a dilution factor of 1:80). Pathway-specific PRS analysis identified the significant enrichment of SLE-risk effects in nine pathways, such as signalling related to reactive oxygen species production, T cell receptor, B cell receptor, and cytokines, in ANA-positive preclinical individuals (P adjusted < 0.05)., Conclusions: Our findings illustrate that the genetic burden of SLE may lead to a crucial transition from normal to preclinical autoimmune conditions prior to the pathogenic stage by increasing the susceptibility to and levels of ANAs., Competing Interests: Competing interests All authors declare they have no competing interests., (Copyright © 2025 European Alliance of Associations for Rheumatology (EULAR). Published by Elsevier B.V. All rights reserved.)

To evaluate the incidence and risk of cardiovascular disease (CVD) among Korean patients with systemic lupus erythematosus (SLE) comparing them to diabetes patients and the general population. This nationwide cohort study focused on incident SLE patients aged over 40 years, matched with diabetes patients and the general population (1:4:4 ratio). CVD was defined as ischaemic heart disease, ischaemic stroke, and cardiac arrest. Incidence rate and incidence rate ratio (IRR) of CVD were calculated using generalised estimating equation models. The Fine-Gray model assessed risk factors for CVD in both SLE and diabetes patients. The study included 4272 incident SLE patients, 17,003 diabetes patients, and 17,088 from the general population. SLE patients had higher CVD risk compared to the general population, with adjusted IRRs of 1.99 for overall CVD. Diabetes patients showed increased CVD risk, but to a lesser extent, with an IRR of 1.39. SLE patients aged 40-59 years displayed a significantly elevated CVD risk. Advanced age, male gender, and current use of glucocorticoids, immunosuppressive, and anti-platelet agents were associated with increased CVD risk in SLE patients. SLE patients have a higher risk of CVD compared to the general population, more so than diabetes patients., Competing Interests: Declarations. Competing interests: The authors declare no competing interests. Ethical approval and Consent to Participate: The data used in this study were obtained from the National Health Insurance Service (NHIS) database, which does not contain information that can directly identify individuals or link subjects through identifiers. Consequently, the Institutional Review Board (IRB) of Hanyang University Hospital (IRB file No. HYUH 2020–05-041) granted an exemption from review. The requirement for informed consent was also waived by the Hanyang University Hospital IRB due to the use of de-identified data. This study was conducted in accordance with the ethical standards of the Declaration of Helsinki., (© 2025. The Author(s).)

Background: To investigate cancer incidence and the potential influence of immunosuppressive agents in Korean systemic lupus erythematosus (SLE) patients., Methods: We conducted a retrospective analysis utilizing data from the Korea Healthcare Bigdata Linked Platform, which integrated the National Central Cancer Registry and National Health Insurance Service databases covering the period 2008-2017. Incidence rates (IRs) per 10,000 person-years (PYs) for site-specific cancers of SLE patients were calculated using ICD-O-3 codes. Multivariable logistic regression analysis was utilized to assess the association between immunosuppressive agents and cancer development in SLE patients., Results: A total of 10,013 predominantly female (91%) Korean SLE patients with a mean age of 36.9 ± 15.2 years were included. During a follow-up of 62,268.5 PYs, 368 patients developed cancer. The IRs per 10,000 PYs for total, solid, and hematologic cancers were 59.07, 54.09, and 5.78, respectively. The most prevalent cancers (measured in IRs per 10,000 PYs) were thyroid (17.01, 95% CI 13.78-20.25), breast (8.67, 95% CI 6.36-10.98), stomach (4.49, 95% CI 2.83-6.16), colorectal (4.17, 95% CI 2.57-5.78), and cervical (3.85, 95% CI 2.31-5.39). Approximately half (50.8%) of SLE patients with cancer were diagnosed at the localized Surveillance, Epidemiology, and End Results (SEER) stage. No statistically significant association was found between immunosuppressive agents and cancer development (Odds Ratio 1.03, 95% CI 0.80-1.34)., Conclusion: Our study shows that Korean SLE patients using immunosuppressive agents are not significantly more likely to develop cancer. Further research with extended observation is warranted to corroborate these findings., Competing Interests: Declarations. Ethics approval and consent to participate: The databases extracted from NHID could not be identified directly or through identifiers linked to the subjects. Therefore, our study was exempted by the Institutional Review Board (IRB) of Hanyang University Hospital (IRB file NO. HYUH 2020–05-041). Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Ankylosing spondylitis (AS) is a chronic inflammatory disease affecting the axial skeleton, resulting in severe pain, decreased mobility, and irreversible structural damage. This study explores the evolving prevalence, patient demographics, and treatment trends for AS in the Korean population from 2010 to 2023, alongside advancements in targeted therapies. This population-based study utilized data from the National Health Insurance Database covering 2010 to 2023. AS cases were identified using at least two ICD-10 (International Classification of Diseases, 10th Revision) codes and rare intractable disease registration codes, excluding diagnoses of rheumatoid arthritis and systemic lupus erythematosus. The annual prevalence of AS was calculated and standardized to the 2017 population. Patient characteristics, comorbidities, and treatment patterns were assessed. The prevalence of AS increased from 26.76 per 100,000 individuals in 2010 to 81.87 per 100,000 in 2023. The proportion of patients over 50 years rose from 19.5 to 32.5%, and female representation increased from 17.9 to 24.0%. Comorbidities such as metabolic syndrome and musculoskeletal complications became more prevalent. Tumor necrosis factor-alpha inhibitor prescriptions rose from 29.7 to 41.6%, while the use of conventional synthetic disease-modifying antirheumatic drugs declined. The introduction of interleukin-17 and Janus kinase (JAK) inhibitors, particularly as second- and third-line therapies, marked a significant development. The prevalence of AS has surged between 2010 and 2023, particularly among older and female patients. The concurrent rise in comorbidities underscores the need for integrated care. Future research should focus on optimizing therapeutic sequences and evaluating long-term outcomes in this changing patient population., Competing Interests: Declarations. Consent for publication: The use of secondary claims data permitted the study to obtain a waiver of informed consent. Competing interests: The authors declare no competing interests. Ethical approval and consent to participate: The study protocol received an exemption from review by the Institutional Review Board at Hanyang University due to its use of anonymized secondary data (IRB No: HYUH202401047-HE001), and informed consent requirements were waived. Ethical statement: The study protocol was exempted from review by the Institutional Review Board of Hanyang University, as it involved the use of anonymized secondary data (IRB No: HYUH202401047-HE001). The requirement for informed consent was also waived., (© 2025. The Author(s).)

Analysis of healthcare utilization, such as hospitalization duration and medical costs, is crucial for policymakers and doctors in experimental and epidemiological investigations. Herein, we examine the healthcare utilization data of patients with systemic lupus erythematosus (SLE). The characteristics of the SLE data were measured over a 10-year period with outliers. Multivariate linear models with multivariate normal error distributions are commonly used to evaluate long series of multivariate longitudinal data. However, when there are outliers or heavy tails in the data, such as those based on healthcare utilization, the assumption of multivariate normality may be too strong, resulting in biased estimates. To address this, we propose multivariate t-linear models (MTLMs) with an autoregressive moving-average (ARMA) covariance matrix. Modeling the covariance matrix for multivariate longitudinal data is difficult since the covariance matrix is high dimensional and must be positive-definite. To address these, we employ a modified ARMA Cholesky decomposition and hypersphere decomposition. Several simulation studies are conducted to demonstrate the performance, robustness, and flexibility of the proposed models. The proposed MTLMs with ARMA structured covariance matrix are applied to analyze the healthcare utilization data of patients with SLE., (© 2024 John Wiley & Sons Ltd.)

Background: This study aimed to identify key priorities for the development of guidelines for information and communication technology (ICT)-based patient education tailored to the needs of patients with rheumatic diseases (RDs) in the Republic of Korea, based on expert consensus., Methods: A two-round modified Delphi study was conducted with 20 rheumatology, patient education, and digital health literacy experts. A total of 35 items covering 7 domains and 18 subdomains were evaluated. Each item was evaluated for its level of importance, and the responses were rated on a 4-point Likert scale. Consensus levels were defined as "high" (interquartile range [IQR] ≤ 1, agreement ≥ 80%, content validity ratio [CVR] ≥ 0.7), "Moderate" (IQR ≥ 1, agreement 50-79%, CVR 0.5-0.7), and "Low" (IQR > 1, agreement < 50%, CVR < 0.5)., Results: Strong consensus was reached for key priorities for developing guidelines in areas such as health literacy, digital health literacy, medical terminology, user interface, and user experience design for mobile apps. Chatbot use and video (e.g., YouTube) also achieved high consensus, whereas AI-powered platforms such as ChatGPT showed moderate-to-high agreement. Telemedicine was excluded because of insufficient consensus., Conclusion: The key priorities identified in this study provide a foundation for the development of ICT-based patient education guidelines for RDs in the Republic of Korea. Future efforts should focus on integrating digital tools into clinical practice to enhance patient engagement and improve clinical outcomes., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2025 The Korean Academy of Medical Sciences.)

Objectives: To estimate the direct healthcare cost progression from before to after systemic lupus erythematosus (SLE) diagnosis and to compare healthcare costs by disease severity., Methods: Patients with incident SLE diagnosed between 2008 and 2018 were identified from the Korean National Health Insurance database. Annual direct healthcare costs for 5 years before and after SLE were estimated and compared with those of age-, sex- and calendar month-matched (1:4) controls, without SLE. Direct healthcare costs were compared by disease severity of SLE using regression analysis., Results: Among 11 173 patients with SLE and 45 500 subjects without SLE, annual direct healthcare costs per person increased in the year before SLE diagnosis and peaked in the first year after diagnosis. They were 7.7-fold greater in the SLE patients than in the subjects without SLE ($5871 vs $759). Severe SLE was associated with 3.284-fold (95% CI: 3.075, 3.507) higher annual costs than mild SLE during the year after diagnosis. Older age (age 60-79 years), lupus nephritis, interstitial lung diseases, and comorbidities such as avascular necrosis and chronic kidney disease were associated with higher annual direct healthcare costs (times [95% CI]) in the first year after diagnosis: age 60-69: 1.119 (1.034, 1.211); age 70-79: 1.470 (1.342, 1.611); lupus nephritis: 1.794 (1.711, 1.881); interstitial lung diseases: 1.435 (1.258, 1.638); avascular necrosis: 6.208 (4.541, 8.487); and chronic kidney disease: 1.858 (1.673, 2.064)., Conclusion: Patients with SLE incurred significantly higher direct healthcare costs than subjects without SLE during the first year after diagnosis. Disease severity, older age, major organ involvements and comorbidities were associated with increased healthcare costs., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objective: This review aimed to map the existing the information and communication technology (ICT)-based patient education for autoimmune inflammatory rheumatic diseases and identify key effectiveness factors and guidelines for professionals., Methods: A scoping review systematically reviewed PubMed, Cochrane library, EMBASE and Web of Science. We designed search strategies to identify ICT-based patient education for autoimmune inflammatory rheumatic diseases focused on rheumatoid arthritis, ankylosing spondylitis, and systemic lupus erythematosus, published between January 2011 and October 2023. Data extraction was independently screened by two reviewers according to the eligibility criteria., Results: Of 13,861 records, 18 met the eligibility criteria. Most studies were randomized controlled trials, primarily conducted in the USA, focusing on rheumatoid arthritis. ICT-based interventions included web-based platforms, aiming to improve self-management, medication adherence, with most interventions showing significant improvements. Digital tools such as websites, chatbots were common. Five groups representing the ICT functions were identified: digital self-management tools, multimedia learning materials, personalized educational sessions, behavior change and empathy games, and interactive online communities and peer support. Most studies lacked theoretical frameworks, or guidelines for developing patient education., Conclusion: ICT-based patient education has significant potential for enhancing self-management and behavior changes in patients with autoimmune inflammatory rheumatic diseases., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Yoon-Kyoung Sung reports financial support was provided by the Ministry of Health & Welfare, Republic of Korea. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Objective: Systemic lupus erythematosus (SLE) is characterised by variability of disease activity patterns over time. This study aimed to investigate the trajectories of SLE disease severity patterns, identify clinical and demographic variables, and assess the association between trajectories of SLE disease severity and all-cause mortality., Methods: A retrospective cohort of newly diagnosed patients with SLE was established using the Korean nationwide healthcare claims information database between 1st January 2008 and 31st December 2016. Using group-based trajectory modelling (GBTM), they were clustered based on the trajectory of SLE disease severity patterns during a two-year follow-up from the cohort entry date. We performed Cox proportional hazards models to compare the mortality between trajectories of SLE disease severity patterns., Results: A total of 8901 patients with SLE were included in the analysis from 2008 to 2016. Five distinct SLE disease severity trajectories were identified as optimal: consistently severe (4.6 %), mild-then-moderate (11.6 %), moderate-then-mild (15.1 %), consistently moderate (30.4 %), and consistently mild (38.3 %). Patients with consistently mild disease severity were more likely to be older; those with consistently severe disease severity were more likely to be male with more comorbidities than other groups. Compared to the consistently mild disease severity, the other trajectory groups showed a higher risk of all-cause mortality., Conclusion: Through GBTM, dynamic two-year severity trajectories of newly diagnosed SLE were identified. Patients' demographics and comorbidities attributed to changes in SLE severity trajectories, which may inform evidence for clinical decision-making., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 Published by Elsevier Ltd.)

Effective management of rheumatoid arthritis (RA) necessitates the accurate measurement of disease activity using a treat-to-target strategy established as a cornerstone approach. Disease activity assessment tools such as the Disease Activity Score in 28 joints (DAS28), Simplified Disease Activity Index, Clinical Disease Activity Index, and Routine Assessment of Patient Index Data 3 have been internationally validated and recognised. In Korea, the government initiated a quality assessment program mandating routine measurement of DAS28 to ensure high-quality RA management. However, whether the DAS28 is the most suitable disease activity measurement tool in the Korean clinical environment is a topic worth considering. In this review, we comprehensively examined disease activity measurement tools and their performance in the Korean context. We also propose a new strategy for measuring RA disease activity, tailored to the different situations encountered by physicians in routine clinical practice. This review may contribute to the improvement of the quality of care for patients with RA in Korea., Competing Interests: CONFLICT OF INTEREST S.K.C. has been an editorial board member of the Journal of Rheumatic Diseases since June 2020, but has no role in the decision to publish this article., (Copyright © 2024 by The Korean College of Rheumatology. All rights reserved.)

Objectives: To determine the risk factors for mortality in Korean patients with rheumatoid arthritis (RA)-associated interstitial lung disease (ILD) in comparison to patients with RA but without ILD (RA-nonILD)., Methods: Data were extracted from a single-centre prospective cohort of RA patients with a chest computed tomography scan at an academic referral hospital in Korea. Patients with RA-ILD enroled between May 2017 and August 2022 were selected, and those without ILD were selected as comparators. The mortality rate was calculated, and the causes of each death were investigated. We used Cox proportional hazard regression with Firth's penalised likelihood method to identify the risk factors for mortality in patients with RA-ILD., Results: A total of 615 RA patients were included: 200 with ILD and 415 without ILD. In the RA-ILD group, there were 15 deaths over 540.1 person-years (PYs), resulting in mortality rate of 2.78/100 PYs. No deaths were reported in the RA-nonILD group during the 1669.9 PYs. The primary causes of death were infection (nine cases) and lung cancer (five cases), with only one death attributed to ILD aggravation. High RA activity (adjusted HR 1.87, CI 1.16-3.10), baseline diffusing capacity for carbon monoxide (DLCO) < 60% (adjusted HR 4.88, 95% CI 1.11-45.94), and usual interstitial pneumonia (UIP) pattern (adjusted HR 5.13, 95% CI 1.00-57.36) were identified as risk factors for mortality in RA-ILD patients., Conclusion: Patients with RA-ILD have an elevated risk of mortality compared with those without ILD. Infection-related deaths are the main causes of mortality in this population. High RA activity, low DLCO, and the UIP pattern are significantly associated with the mortality in patients with RA-ILD., (© 2024. The Author(s).)

Background: To evaluate the effectiveness of Korean Red Ginseng (KRG) in managing fatigue in Korean patients with rheumatic diseases., Methods: Patients were randomly assigned to KRG (2 g/day, n = 60) or placebo (n = 60) groups for 12 weeks of blind phase and then open-label KRG from weeks 12 to 24 (placebo-KRG, continuous-KRG). The primary outcome was the improvement rate in fatigue, defined by an increase in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue scores at 12 weeks. Secondary outcomes included changes in FACIT-Fatigue and fatigue visual analog scale (VAS) between 0 and 12 weeks and those changes in both indices at 24 weeks., Results: The study enrolled 120 patients (Sjogren syndrome [n = 53], rheumatoid arthritis [n = 43], or both diseases [n = 24]). The mean age was 50.9 ± 11.6 years, with 97.5% being female. Baseline characteristics were similar between the two groups. The improvement rate in FACIT-Fatigue after 12 weeks was higher in the KRG group than in the placebo group, but the difference was statistically insignificant (38.3% vs. 26.7%, p = 0.242). Improvement in fatigue was observed in both groups by increases in FACIT-F (4.6 vs. 4.0) and reductions in fatigue VAS (-16.0 vs. -12.2) scores at 12 weeks. The most frequently reported adverse events during KRG use were pruritus and urticarial, with no significant difference between the two groups., Conclusion: Both KRG and placebo groups showed significant reductions in fatigue. KRG treatment for 24 weeks did not reduce fatigue symptoms more than the placebo in patients with rheumatic diseases.

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., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objectives: We aimed to investigate medication utilisation trends during pregnancy and identify factors associated with adverse pregnancy outcomes (APOs) in patients with rheumatoid arthritis (RA)., Methods: Female patients with RA aged 20-50 years were identified from the Korean national health insurance database between 2010 and 2020. Pregnancy episodes were divided into two groups according to pregnancy outcome: the delivery group and the APO group (abortion and stillbirth). The characteristics and medication utilisation patterns were compared between the two groups, and multivariable logistic regression analysis was conducted to identify the factors associated with APOs., Results: A total of 5728 pregnancy episodes were included, comprising 4576 delivery episodes and 1152 APO episodes. The mean maternal age for all pregnancy episodes was 33.7 years; 33.3 years in the delivery group and 33.7 years in the APO group. Hydroxychloroquine was the most commonly used conventional synthetic disease-modifying antirheumatic drug (DMARD) during the preconception period and pregnancy in both groups. The prescription rate of all DMARDs decreased rapidly during pregnancy. In the multivariable analysis, use of methotrexate (adjusted OR (aOR): 2.14, 95% CI 1.57 to 2.92) and leflunomide (aOR: 2.68, 95% CI 1.39 to 5.15) within 3 months before conception was associated with APOs., Conclusion: Methotrexate and leflunomide are associated with an increased possibility of APOs, emphasising the importance of appropriate medication adjustment when planning for pregnancy., Competing Interests: Competing interests: Y-KS has received research grants from Bristol-Myers Squibb, Eisai, Pfizer and JW Pharmaceutical. DHY has received research grants from Celltrion, has served as an outside board of Celltrion and is on the speakers’ bureau of Celltrion and Celltrion Healthcare., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The strongest genetic risk factor for rheumatoid arthritis (RA) has been known as HLA-DRB1 based on amino acid positions 11, 71, and 74. This study analyzed the association between specific HLA-DRB1 locus and treatment response to abatacept or TNF inhibitors (TNFi) in patients with seropositive RA. A total of 374 Korean RA patients were treated with abatacept (n = 110) or TNFi (n = 264). Associations between HLA-DRB1 and treatment response after 6 months were analyzed using multivariable logistic regression. Seropositive RA patients with HLA-DRB1 shared epitope (SE) had a favorable response to abatacept (OR = 3.67, P = 0.067) and an inversely associated response to TNFi (OR 0.57, P = 0.058) based on EULAR response criteria, but the difference was not statistically significant in comparison to those without SE. In analyses using amino acid positions of HLA-DRB1, a significant association was found between valine at amino acid position 11 of SE and good response to abatacept (OR = 6.46, P = 5.4 × 10 -3 ). The VRA haplotype also showed a good response to abatacept (OR = 4.56, P = 0.013), but not to TNFi. Our results suggest that treatment response to abatacept or TNFi may differ depending on HLA-DRB1 locus in seropositive RA, providing valuable insights for selecting optimal therapy., (© 2024. The Author(s).)

To determine the increased risk of major adverse cardiovascular events (MACE) in patients with systemic lupus erythematosus (SLE) compared to the general population in Korea. Using data from the National Health Insurance Service database spanning 2008 to 2018, incident SLE patients aged 18 years and above were selected along with a 1:4 age- and sex-matched control group. The crude incidence rate (IR) of MACE was calculated as the number of events per 1000 person-years and the IR ratio (IRR) for MACE was adjusted using generalized estimating equations. Subgroup analysis was conducted to evaluate the risk differences of overall MACE and its composites based on age and sex stratification. The study included 8568 SLE patients and 34,272 controls. The cumulative IR of MACE per 1000 person-years in SLE patients and controls were 4.08 and 1.30, respectively. After adjusting for confounders, SLE patients had a higher risk of MACE compared to the general population (adjusted IRR of 2.40 [95% confidence interval [CI] 1.88-3.05]), with no gender differences observed. The increased risk of MACE in SLE patients was highest in the 18-39 age group (IRR 11.70, 95% CI 5.95-23.01) and gradually decreased with age. The increased risk of ischemic stroke (IRR 2.41, 95% CI 1.84-3.15) and myocardial infarction (IRR 2.19, 95% CI 1.30-3.68) in SLE patients was comparable. The risk of MACE in SLE patients is 2.40 times higher than that of the general population, with a higher relative risk observed in younger individuals., (© 2024. The Author(s).)

Objectives: This study developed an algorithm for identifying pregnancy episodes and estimating the last menstrual period (LMP) in an administrative claims database and applied it to investigate the use of pregnancy-incompatible immunosuppressants among pregnant women with systemic lupus erythematosus (SLE)., Methods: An algorithm was developed and applied to a nationwide claims database in Korea. Pregnancy episodes were identified using a hierarchy of pregnancy outcomes and clinically plausible periods for subsequent episodes. The LMP was estimated using preterm delivery, sonography, and abortion procedure codes. Otherwise, outcome-specific estimates were applied, assigning a fixed gestational age to the corresponding pregnancy outcome. The algorithm was used to examine the prevalence of pregnancies and utilization of pregnancy-incompatible immunosuppressants (cyclophosphamide [CYC]/mycophenolate mofetil [MMF]/methotrexate [MTX]) and non-steroidal anti-inflammatory drugs (NSAIDs) during pregnancy in SLE patients., Results: The pregnancy outcomes identified in SLE patients included live births (67%), stillbirths (2%), and abortions (31%). The LMP was mostly estimated with outcome-specific estimates for full-term births (92.3%) and using sonography procedure codes (54.7%) and preterm delivery diagnosis codes (37.9%) for preterm births. The use of CYC/MMF/MTX decreased from 7.6% during preconception to 0.2% at the end of pregnancy. CYC/MMF/MTX use was observed in 3.6% of women within 3 months preconception and 2.5% during 0-7 weeks of pregnancy., Conclusions: This study presents the first pregnancy algorithm using a Korean administrative claims database. Although further validation is necessary, this study provides a foundation for evaluating the safety of medications during pregnancy using secondary databases in Korea, especially for rare diseases.

Objective: To compare the risk of end-stage renal disease (ESRD) between patients with early-onset lupus nephritis (EOLN) and those with delayed-onset LN (DOLN)., Methods: This retrospective study of incident cases of systemic lupus erythematosus (SLE) used nationwide Korean claims databases and data from 2008 through 2018. We divided LN patients into two groups: the EOLN group (with LN onset within 12 months of SLE diagnoses) and the DOLN group (with LN onset later than 12 months after SLE diagnoses). Patients were observed from the date of LN diagnosis to the development of ESRD, death, or the last follow-up. Cox proportional hazards modeling was used to predict hazard ratios (HRs) for progression to ESRD with death as a competing risk., Results: We identified 3779 incident SLE patients who developed LN during follow-up: 60 % (n = 2281) had EOLN, and 40 % (n = 1489) had DOLN. Sixty-nine patients with EOLN (3.0 %) and 29 patients with DOLN (1.9 %) progressed to ESRD. After adjusting for confounders, the ESRD risk associated with EOLN was comparable to the risk associated with DOLN (HR 1.10, 95 % confidence interval [CI] 0.57 to 2.11). In the subgroup of patients on aggressive immunosuppressive therapy (670 with EOLN and 179 with DOLN), the ESRD risk was higher in the DOLN group (HR 2.6, 95 % CI 1.11 to 6.10)., Conclusion: The risk of ESRD was comparable between patients with EOLN and DOLN. However, among patients on aggressive immunosuppressive therapy, compared with EOLN, DOLN was associated with a higher risk of progression to ESRD., Competing Interests: Declaration of Competing Interest YKS has received research grants from Bristol-Myers Squibb, Eisai, Pfizer, and JW Pharmaceutical. Other authors declare that there is no conflict of interest., (Copyright © 2023. Published by Elsevier Inc.)

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by diverse organ system disabilities, predominantly affecting young females. The clinical manifestations of SLE encompass various organs, including the kidney, cardiovascular system, and central nervous system. Young females with SLE experience higher mortality rates than the general population, making it imperative to gain insights into the disease patterns and associated factors. The current review examines the epidemiological studies to analyze the prevalence, incidence, and mortality trends of SLE in Korea and compares them with the findings from other countries. We aim to identify potential similarities, differences, and factors contributing to the burden of SLE in different populations by exploring the comparative epidemiological aspects. The knowledge derived from this comparison would aid in advancing the overall management of SLE in Korea., Competing Interests: CONFLICT OF INTEREST S.K.C. has been an editorial board member since June 2020, but has no role in the decision to publish this article., (Copyright © 2023 by The Korean College of Rheumatology. All rights reserved.)

Objective: There was a safety concern about an increased risk of thromboembolic events in patients with rheumatoid arthritis (RA) treated with Janus kinase inhibitors (JAKis). This study aimed to determine the risk of venous thromboembolism (VTE) in Korean patients with RA treated with JAKis compared with tumour necrosis factor (TNF) inhibitors., Methods: Using the National Health Insurance Service database between 2015 and 2019, patients with prevalent RA who started JAKi or TNF inhibitor were selected as the study population. All participants were naïve to targeted therapy. Patients that had experienced any VTE event or used anticoagulant agents within 30 days were excluded. Demographic and clinical characteristics were all balanced by stabilised inverse probability of treatment weighting (sIPTW) using propensity score. The Cox proportional hazard model considering death as a competing risk was used to evaluate the risk of VTE in JAKi users compared with TNF inhibitor users., Results: A total of 4,178 patients were included: 871 JAKi users and 3,307 TNF inhibitor users were followed up for 1,029.2 person-years (PYs) and 5,940.3 PYs, respectively. With a balanced sample after sIPTW, the incidence rates (IR) of VTE were 0.06 per 100 PYs (95% confidence interval [CI] 0.00-1.23) in JAKi users and 0.38 per 100 PYs (95% CI 0.25-0.58) in TNF inhibitor users. The hazard ratio was 0.18 (95% CI 0.01-3.47) after adjusting for unbalanced variables after performing sIPTW., Conclusion: There is no increased risk of VTE in RA patients treated with JAKis compared with TNF inhibitors in Korea., Competing Interests: Declaration of Competing Interest YKS has received research grants from Bristol-Myers Squibb, Eisai, Pfizer, and JW Pharmaceutical. Other authors declare that there are no conflicts of interest., (Copyright © 2023. Published by Elsevier Inc.)

Cellular endocytosis is an essential phenomenon which induces cellular reactions, such as waste removal, nutrient absorption, and drug delivery, in the process of cell growth, division, and proliferation. To observe capacitance responses upon endocytosis on a single-cell scale, this study combined an optical tweezer that can optically place a single cell on a desired location with a capacitance sensor and a cell incubation chamber. Single HeLa cancer cell was captured and moved to a desired location through optical trapping, and the single-cell capacitance change generated during the epidermal growth factor (EGF) molecule endocytosis was measured in real time. It was found that single HeLa cells showed a larger increase in capacitance values compared to that of the single NIH3T3 cells when exposed to varying EGF concentrations. In addition, the capacitance change was in proportion to the cell's EGF receptor (EGFR) level when cells of different levels of EGFR expression were tested. An equation derived from these results was able to estimate the EGFR expression level of a blind-tested cell. The biosensor developed in this research can not only quickly move a single cell to a desired location in a non-invasive manner but also distinguish specific responses between cancer and normal cells by continuous measurement of real-time interactions of a single cell in culture to the external ligands., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background/aims: We aimed to compare the effectiveness and safety of Janus kinase inhibitors (JAKi) vs. biologic disease- modifying antirheumatic drugs (bDMARD) in Korean patients with rheumatoid arthritis (RA) who had an inadequate response to conventional synthetic DMARDs., Methods: A quasi-experimental, multi-center, prospective, non-randomized study was conducted to compare response rates between JAKi and bDMARDs in patients with RA naïve to targeted therapy. An interim analysis was performed to estimate the proportion of patients achieving low disease activity (LDA) based on disease activity score (DAS)-28- erythroid sedimentation rate (ESR) (DAS28-ESR) at 24 weeks after treatment initiation and to evaluate the development of adverse events (AEs)., Results: Among 506 patients enrolled from 17 institutions between April 2020 and August 2022, 346 (196 JAKi group and 150 bDMARD group) were included in the analysis. After 24 weeks of treatment, 49.0% of JAKi users and 48.7% of bDMARD users achieved LDA (p = 0.954). DAS28-ESR remission rates were also comparable between JAKi and bDMARD users (30.1% and 31.3%, respectively; p = 0.806). The frequency of AEs reported in the JAKi group was numerically higher than that in the bDMARDs group, but the frequencies of serious and severe AEs were comparable between the groups., Conclusion: Our interim findings reveal JAKi have comparable effectiveness and safety to bDMARDs at 24 weeks after treatment initiation.

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., (© 2023. The Author(s).)

Background: To introduce a prospective cohort for rheumatoid arthritis (RA) patients with interstitial lung disease (ILD) and to identify their clinical features in comparison with RA patients without ILD., Methods: Using a multidisciplinary collaborative approach, a single-center cohort for RA patients with ILD (RA-ILD) was established in May 2017, and enrolment data from May 2017 to March 2021 were used to compare the clinical features of RA patients without ILD (RA-non ILD). Multivariable logistic regression analysis was used to identify factors associated with ILD in RA patients., Results: Among 148 RA-ILD and 410 RA-non ILD patients, participants in the RA-ILD group were older (65.8 ± 9.9 vs. 58.0 ± 10.4 years, P < 0.001) and included more males (35.8% vs. 14.6%, P < 0.001) than in the RA-non ILD group. The RA-ILD group had a higher proportion of late-onset RA patients (age ≥ 60 years) than in the comparator group (43.9% vs. 14.2%, P < 0.001). Multivariable logistic regression analysis showed that higher age at RA onset (OR 1.056, 95% CI 1.021-1.091), higher body mass index (BMI; OR 1.65, 95% CI 1.036-2.629), smoking history (OR 2.484, 95% CI 1.071-5.764), and oral glucocorticoid use (OR 3.562, 95% CI 2.160-5.874) were associated with ILD in RA patients, whereas methotrexate use was less likely to be associated with ILD (OR 0.253, 95% CI 0.155-0.412)., Conclusions: Higher age at RA onset, smoking history, and higher BMI were associated with the presence of ILD among RA patients. Oral glucocorticoids were more frequently used whereas methotrexate was less likely to be used in RA-ILD patients., (© 2023. The Author(s).)

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., Competing Interests: DHY has received research grants from Celltrion, has served as a consultant for Celltrion, and is on the speakers’ bureau of Celltrion and Celltrion Healthcare. YKS has received research grants from Bristol-Myers Squibb, Eisai, Pfizer, and JW Pharmaceutical. There are no patents, and no products in development or being marketed to declare. This does not alter our adherence to PLOS ONE policies on sharing data and materials. Other authors declare no conflicts of interest., (Copyright: © 2023 Song et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objective: To determine the risk of malignancy in Korean patients with rheumatoid arthritis (RA) receiving Janus kinase inhibitors (JAKis) compared with tumour necrosis factor inhibitors (TNFis)., Methods: A retrospective cohort of patients with RA initiating their first JAKi or TNFi was established using the Korean National Health Insurance database between 2015 and 2019. They were followed up from treatment initiation to the occurrence of malignancy, drug discontinuation, death or until December 2019. Baseline features of the patients were balanced through inverse probability of treatment weighting (IPTW) using a propensity score. A Cox proportional hazard model was established to estimate the HR for malignancy risk in JAKi users compared with TNFi users., Results: A total of 4929 patients (1064 JAKi-treated and 3865 TNFi-treated patients) were included, and the observation periods were 1288.6 person-years (PYs) for JAKi users and 6823.8 PYs for TNFi users. The incidence rates of overall malignancy were 0.54 per 100 PYs (95% CI 0.26 to 1.14) in JAKi users and 0.85 per 100 PYs (95% CI 0.66 to 1.10) in TNFi users. In IPTW analysis with a balanced sample (4101 JAKi-treated and 5131 TNFi-treated patients), HR was 0.83 (95% CI 0.55 to 1.27) for overall malignancy: 0.77 (95% CI 0.50 to 1.19) for solid malignancy and 2.86 (95% CI 0.41 to 20.00) for haematological malignancy., Conclusion: Malignancy risk in Korean patients with RA was not increased with JAKi use compared with TNFi use., Competing Interests: Competing interests: Y-KS has received research grants from Bristol-Myers Squibb, Eisai, Pfizer and JW Pharmaceutical. Other authors declare no conflict of interest., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: MUC5B variant rs35705950 is the common and most significant risk variant for rheumatoid arthritis-interstitial lung disease (RA-ILD) in Western populations. However, little is known about its significant association with RA-ILD in Asian populations. We here investigate the association of rs35705950 with Korean patients with RA-ILD., Methods: In this cross-sectional study, we genotyped rs35705950 in 2444 patients with RA. Among them, 683 patients with RA who have chest CT were divided into RA-ILD and RA-noILD. RA-ILD was classified as usual interstitial pneumonia (UIP) and other than UIP. The associations of rs35705950 with RA-ILD and its subtype were analysed using multivariable regression adjusted for age at RA diagnosis. Meta-analysis of a previously reported Japanese dataset and Korean dataset obtained for this study was conducted., Results: The minor allele (T) frequency of rs35705950 was 0.37%, 1.43% and 2.38% in 2444 patients with RA, 105 patients with RA-ILD and 63 patients with UIP, respectively. Genotypic association of rs35705950 with RA-ILD was insignificant (OR 2.49, 95% CI 0.64 to 9.69, p=0.187), but showed significant association with UIP (OR 4.90, 95% CI 1.23 to 19.59, p=0.024) compared with RA-noILD. In meta-analysis (123 UIP and 878 RA-noILD) combining our data with previously reported Japanese data, this variant was found to be significantly associated with UIP (OR 3.51, 95% CI 1.19 to 10.37, p=0.023)., Conclusion: MUC5B variant rs35705950 is a rare but significant risk factor for Asian patients with RA-ILD with UIP, suggesting a sharing of the genetic background between Asian and Western populations., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

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., (© 2022 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.)

Objective: To establish the reliability and validity of the Korean version of LupusPRO version 1.7 (v1.7) for systemic lupus erythematosus (SLE) patients., Methods: LupusPRO v1.7 was translated into Korean, followed by pretesting among five native Korean speakers. We administered the LupusPRO v1.7 survey to five SLE patients and made minor changes to clarify the language. Then, 133 SLE patients participated in the validation procedure. In each domain, the internal consistency reliability (ICR) and test-retest reliability (TRR) were assessed using Cronbach's alpha and the intra-class correlation coefficient (ICC), respectively. Criterion validity was evaluated using Spearman's correlation coefficient with the other measures such as SF-36, EQ-5D VAS, and SELENA-SLEDAI PGA. Construct validity was assessed by confirmatory factor analysis (CFA) using the unweighted least square estimation method., Results: The mean age of the 133 patients was 36.14 years, and 97% of them were women. Analysis of 130 returned questionnaires revealed that most ICRs of the Korean LupusPRO v1.7 domains were acceptable, with Cronbach's alphas in the range of 0.579-0.949, and most TRRs were good with ICCs from 0.582 to 0.851. Criterion validities presented significant correlations between the LupusPRO v1.7 and other measures validated. In the analysis of the CFA model, the goodness of fit indices demonstrated an acceptable fit. Factor loadings for most individual items were between 0.548 and 0.985. The average variance extracted (AVE) and composite reliability (CR) of most domains were greater than 0.5 and 0.7, respectively, demonstrating acceptable convergent and discriminant validities., Conclusions: The Korean version of LupusPRO v.17 had acceptable reliability and validity.

Background: To investigate the use of cyclooxygenase-2 (COX-2) inhibitors as an initial drug treatment for knee osteoarthritis (OA) patients., Methods: From 2013 to 2015, patients with knee OA were identified from the Korean nationwide claims database. Among them, we extracted incident cases of knee OA to identify the initial drug treatment. Trends in the use of non-steroid anti-inflammatory drugs (NSAIDs) including COX-2 inhibitors were analyzed during the first year after their diagnosis. Associated factors for COX-2 inhibitor use were examined using a multivariate logistic regression model., Results: We identified 2,857,999 incident knee OA patients (955,259 in 2013, 981,314 in 2014, and 921,426 in 2015). The mean ± standard deviation age of patients was 64.2 ± 9.8 years. The frequency of COX-2 inhibitor use as initial treatment increased from 3.5% in 2013 to 7.2% in 2015 ( P < 0.01). In patients taking the medication regularly for one year after diagnosis (medication possession ratio ≥ 50%), COX-2 inhibitor use also rapidly increased from 5.5% in 2013 to 11.1% in 2015 ( P < 0.01). However, the frequencies of non-selective NSAID and analgesic use did not decrease remarkably. Factors associated with patients using COX-2 inhibitors on initial drug treatment were older age (odds ratio [OR], 1.08), female (OR, 1.24), and comorbidity (OR, 1.03). Type of institution, physician speciality, and insurance type of patients were also associated., Conclusion: In Korea, COX-2 inhibitors have rapidly increased as an initial treatment for knee OA patients, but it has not appeared to reduce the use of non-selective NSAIDs and analgesics., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2022 The Korean Academy of Medical Sciences.)

Nanoparticles consisting of a condensed nucleic acid core surrounded by protective layers which aid to overcome extracellular and intracellular hurdles to gene delivery (i. e., core-shell nanoparticles, CSNPs) synthetically mimic viruses. The outer shells shield the core and are particularly designed to enable facilitated release of the gene payload into the cytoplasm, the major limiting step in intracellular gene delivery. The hypothetical proton sponge effect and degradability in response to a stimulus (i. e., mildly acidic pH in the endosome) are two prevailing, although contested, principles in designing effective carriers for intracellular gene delivery via endosomal escape. Utilizing the highly flexible chemical-tuning of the polymeric shell via surface-initiated photo-polymerization of the various monomers at different molecular ratios, the effects of proton buffering capacity, acid-degradability, and endosomal membrane-lysis property on intracellular delivery of plasmid DNA by CSNPs were investigated. This study demonstrated the equivalently critical roles of proton buffering and acid-degradability in achieving efficient intracellular gene delivery, independent of cellular uptake. Extended proton buffering resulted in further improved transfection as long as the core structure was not compromised. The results of the study present a promising synthetic strategy to the development of an efficient, chemically-tunable gene delivery carrier., (© 2022 Wiley-VCH GmbH.)

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., (© 2021. The Author(s).)

Objective: To determine the risk of herpes zoster (HZ) in Korean patients with rheumatoid arthritis (RA) receiving Janus kinase inhibitors (JAKis)., Methods: We performed a nested case-control study with 1:10 matching for sex and age using single-centre prospective cohorts of patients with RA receiving targeted therapy in Korea. Then we performed conditional logistic regression analyses to determine the risk associated with JAKi use compared with biologic disease-modifying antirheumatic drug (bDMARD) use, with adjusting for various factors. We also used logistic regression analysis to identify other risk factors for the development of HZ in JAKi users., Results: From a total of 1147 patients, 61 cases and 610 matched controls were selected. In conditional logistic regression analysis, JAKi use did not increase the risk of HZ development (OR 1.35, 95% CI 0.70 to 2.61) after adjusting for other factors. Rather, duration of RA less than 10 years (OR 0.54, 95% CI 0.30 to 0.97) and having had three or more previous targeted therapies (OR 5.29, 95% CI 1.45 to 19.31) were risk factors for HZ. Among JAKi users, higher disease activity score 28-erythrocyte sedimentation rate (DAS28-ESR) (OR 1.44, 95% CI 1.06 to 1.97) was identified as a risk factor in addition to three or more previous targeted therapies (OR 10.12, 95% CI 1.92 to 53.49)., Conclusions: The number of previous targeted therapies, but not JAKi use, was identified as a risk factor for HZ development in Korean patients with RA in a real-world setting. High disease activity was an additional risk factor for JAKi users., Competing Interests: Competing interests: Y-KS has received research grants from Bristol-Myers Squibb, Eisai, Pfizer and JW Pharmaceutical. Other authors declare that there is no conflict of interest., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: This study aimed to evaluate the crude incidence rates and relative risk of malignancy in Korean patients with SLE., Methods: We conducted a retrospective nationwide cohort study using databases from the National Health Insurance Service in Korea. All prevalent SLE patients aged over 19 were identified from January 2012 to December 2014 and observed until the diagnosis of malignancy, death, or end of the study, December 2015. The crude incidence rates (IRs) and standardised incidence ratios (SIRs) of overall and site-specific malignancies in SLE patients were estimated., Results: We identified 17,854 SLE patients and during the observation period (60,511 person-years [PYs]), 768 solid malignancies (126.9/10,000 PYs) and 68 haematologic malignancies (11.2/10,000 PYs) occurred in SLE patients. In SLE patients, breast and reproductive system and thyroid cancers occurred predominantly, followed by liver and colon cancers. The SIRs of overall, solid, and haematologic malignancies of SLE patients compared to the general population were 1.8 (95% confidence interval [CI] 1.6-1.9), 1.7 (95% CI 1.5-1.8), and 5.9 (95% CI 4.8-7.3), respectively. In solid malignancies, head and neck (2.7, 95% CI 1.1-4.2), bladder (2.4, 95% CI 1.1-3.8), liver (1.9, 95% CI 1.4-2.3), pancreas (1.9, 95% CI 1.3-2.6), lung (1.8, 95% CI 1.2-2.4), colon (1.7, 95% CI 1.3-2.2), thyroid (1.6, 95% CI 1.3-1.8) and breast and reproductive system (1.5, 95% CI 1.2-1.7) cancers are at increased risk in SLE patients., Conclusion: An increased risk of haematologic and solid malignancies was observed in Korean patients with SLE compared to the general population., (© 2021. The Author(s).)

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., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2021 The Korean Academy of Medical Sciences.)

Electrical impedance biosensors combined with microfluidic devices can be used to analyze fundamental biological processes for high-throughput analysis at the single-cell scale. These specialized analytical tools can determine the effectiveness and toxicity of drugs with high sensitivity and demonstrate biological functions on a single-cell scale. Because the various parameters of the cells can be measured depending on methods of single-cell trapping, technological development ultimately determine the efficiency and performance of the sensors. Identifying the latest trends in single-cell trapping technologies afford opportunities such as new structural design and combination with other technologies. This will lead to more advanced applications towards improving measurement sensitivity to the desired target. In this review, we examined the basic principles of impedance sensors and their applications in various biological fields. In the next step, we introduced the latest trend of microfluidic chip technology for trapping single cells and summarized the important findings on the characteristics of single cells in impedance biosensor systems that successfully trapped single cells. This is expected to be used as a leading technology in cell biology, pathology, and pharmacological fields, promoting the further understanding of complex functions and mechanisms within individual cells with numerous data sampling and accurate analysis capabilities.

Objective: To evaluate the risk of non-vertebral fractures in patients with gout compared with those with rheumatoid arthritis (RA)., Methods: Using claims data from Medicare (2008-2015), we conducted a cohort study of patients with gout versus RA matched on age, sex, and index date with a 1:1 ratio. The primary outcome was a composite endpoint of non-vertebral fractures including hip, pelvis, humerus, and wrist identified with the validated algorithms. We also assessed hip fractures separately. Multivariable Cox proportional hazards regression estimated the hazard ratio (HR) for the outcomes in gout versus RA adjusted for 45 covariates., Results: We included a total of 134,157 matched pairs of gout and RA patients (mean age: 73.7 years). Risk factors for fracture were more prevalent in RA, while other comorbidities including obesity, coronary heart disease, hypertension, and diabetes were more common in gout. Over the mean 2.8 years follow-up, the incidence rate (IR)/1000 person-year (PY) of non-vertebral fractures was 10.42 in gout and 15.01 in RA. For hip fractures, the IR/1000 PY was 4.86 in gout and 7.73 in RA. The multivariable HR associated with gout versus RA was 0.84 (95% confidence interval (CI) 0.80-0.88) for non-vertebral fractures and 0.76 (95% CI 0.71-0.82) for hip fractures. Stratified analyses by age, sex, prior fractures, steroid use, and TNF inhibitor use showed similar results., Conclusions: In this large cohort of older patients, gout was associated with a modestly decreased risk of non-vertebral or hip fractures versus RA. However, non-vertebral fractures occurred frequently in both gout and RA.

Backgrounds/aims: This study was performed to reveal the usefulness of the trabecular bone score (TBS) in assessing bone strength in patients with ankylosing spondylitis (AS) in comparison with dual-energy X-ray absorptiometry (DXA) methods., Methods: A total of 215 AS patients (75.8% male) were enrolled from a single university hospital in Korea. Demographic and clinical information were assessed. Patients completed X-rays of the cervical and lumbar spine (L-spine), and spinal ankyloses were quantified using the modified Stoke AS Spine Score (mSASSS). Hip, anteroposterior and lateral L-spine bone mineral density (BMD) and TBS were assessed by DXA methods. Clinical characteristics and bone strength measurement results were compared between male and female AS patients. The accuracy of each bone strength evaluation method in predicting Fracture Risk Assessment Tool (FRAX) scores indicating moderate or higher fracture risk was compared by receiver operating characteristic curves in patients aged ≥ 40 years. Correlations between each bone strength measurement method and mSASSS were examined., Results: Male patients showed higher mSASSS and less prevalent peripheral joint involvement compared to female patients (p < 0.05). TBS, hip BMD, and L-spine lateral BMD showed comparably high areas under the curve (AUCs) for predicting FRAX-major osteoporotic fractures (MOF) ≥ 10% (AUC ranged 0.72 to 0.76). TBS negatively correlated with mSASSS in both male and female patients (p < 0.01)., Conclusion: TBS could predict the risk of MOF and is not influenced by spinal osteoproliferation in AS patients, even in those with advanced spinal changes.

Objective: We aimed to investigate the prevalence, incidence and cause-specific mortality of RA-associated interstitial lung disease (RA-ILD) among older US patients with RA., Methods: We performed a nationwide cohort study using Medicare claims data (parts A, B and D for 2008-2017). RA was identified with a validated algorithm using RA diagnosis codes and DMARD prescription. RA-ILD was identified with a validated algorithm using ILD diagnosis codes by a rheumatologist/pulmonologist. RA-ILD was categorized as prevalent or incident relative to the initial RA observation (baseline/index date). We compared the total mortality of RA-ILD to RA without ILD using multivariable Cox regression, adjusting for baseline covariates. For cause-specific mortality, Fine and Gray subdistribution hazard ratios (sdHRs) were estimated to handle competing risks of alternative mortality causes., Results: Among 509 787 RA patients (mean age 72.6 years, 76.2% female), 10 306 (2.0%) had prevalent RA-ILD at baseline. After baseline, 13 372 (2.6%) developed RA-ILD during 1 873 127 person-years of follow-up (median 3.0 years/person). During follow-up, 38.7% of RA-ILD patients died compared with 20.7% of RA patients without ILD. After multivariable adjustment, RA-ILD had an HR of 1.66 (95% CI 1.60, 1.72) for total mortality. Accounting for competing risk of other causes of death, RA-ILD had an sdHR of 4.39 (95% CI 4.13, 4.67) for respiratory mortality and an sdHR of 1.56 (95% CI 1.43, 1.71) for cancer mortality compared with RA without ILD., Conclusions: RA-ILD was present or developed in nearly 5% of patients in this nationwide study of older patients with RA. Compared with RA without ILD, RA-ILD was associated with excess total, respiratory and cancer mortality that was not explained by measured factors., (© The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Purpose: To identify predictors of low health-related quality of life (HRQoL) and depression in ankylosing spondylitis (AS) patients with a focus on gender differences., Methods: We conducted a cross-sectional cohort study. Both AS-related clinical data and contextual factors were obtained. HRQoL and depressive mood were assessed by EuroQol-5 dimension (EQ-5D) and the Center for Epidemiological Studies Depression Scale (CES-D), respectively. Gender-stratified multivariable logistic regression analyses were performed., Results: Among 211 patients, 161 were males. Males had similar disease activity and higher radiographic damage compared with females. There was no significant difference in EQ-5D index score between genders. CES-D score was higher in females. Higher ASDAS-C-reactive protein (CRP) was associated with low HRQoL in both males (Odds ratio [OR] 4.25, 95% confidence interval [CI] 2.42-7.46) and females (OR 2.94, 95% CI 1.02-8.48). Being employed was associated with decreased possibility of having low HRQoL in males (OR 0.39, 95% CI 0.16-0.95). Regarding depression, higher ASDAS-CRP (OR 1.87, 95% CI 1.03-3.40), current smoking (OR 2.98, 95% CI 1.09-8.15), and being employed (OR 0.17, 95% CI 0.06-0.46) were associated with depression in males. For females, living with a partner was related to depression (OR 0.08, 95% CI 0.01-0.93)., Conclusion: AS patients with high disease activity are likely to be suffering from low HRQoL. Both disease-related factors and contextual factors were associated with depression, and predictors showed some differences between genders. Awareness of gender differences in comprehensive assessment can lead us to better personalized management in AS patients., (© 2021. The Author(s), under exclusive licence to Springer Nature Switzerland AG part of Springer Nature.)

Objective: To evaluate the effectiveness of bazedoxifene in preventing bone loss in patients with rheumatoid arthritis (RA) receiving low-dose glucocorticoids (GCs)., Methods: In this randomized, controlled, open-label study, we assigned postmenopausal women with osteopenia who had been receiving low-dose GCs for RA to two groups: a group receiving bazedoxifene (20 mg/day) with elemental calcium 1200 mg and vitamin D 800 IU daily (bazedoxifene group) and a group receiving the same doses of calcium and vitamin D only (control group). As primary outcome, bone mineral density (BMD) change in the lumbar spine (L-spine) from baseline to 48 weeks was assessed. Changes in BMD in the femur, trabecular bone score, bone turnover markers, and development of fracture were assessed as secondary outcomes. For intention-to-treat analysis, 20 completed data sets were created by applying multiple imputations by chained equations., Results: A total of 114 patients (57 patients in each group) were recruited. A significant increase in L-spine BMD (0.015 g/cm 2 , P = 0.007) was observed in the bazedoxifene group, and the increase was significantly higher than in the control group (0.013, 95% CI 0.0003-0.026, P = 0.047). Reductions in bone turnover markers in the bazedoxifene group were significantly greater than in the control group. Only one fracture was observed in the bazedoxifene group, while four fractures developed in the control group., Conclusion: In postmenopausal patients with RA receiving low-dose GCs, bazedoxifene improved BMD and reduced bone turnover markers. However, the change in BMD did not exceed the least significant change., Trial Registration: ClinicalTrials.gov, NCT02602704 .

Purpose: Accurately identifying patients with psoriasis (PsO) is crucial for generating real-world evidence on PsO disease course and treatment utilization., Methods: We developed nine claims-based algorithms for PsO using a combination of the International Classification of Diseases (ICD)-9 codes, specialist visit, and medication dispensing using Medicare linked to electronic health records data (2013-2014) in two healthcare provider networks in Boston, Massachusetts. We calculated positive predictive value (PPV) and 95% confidence interval (CI) for each algorithm using the treating physician's diagnosis of PsO via chart review as the gold standard. Among the confirmed PsO cases, we assessed their PsO disease activity., Results: The nine claims-based algorithms identified 990 unique patient records. Of those, 918 (92.7%) with adequate information were reviewed. The PPV of the algorithms ranged from 65.1 to 82.9%. An algorithm defined as ≥1 ICD-9 diagnosis code for PsO and ≥1 prescription claim for topical vitamin D agents showed the highest PPV (82.9%). The PPV of the algorithm requiring ≥2 ICD-9 diagnosis codes and ≥1 prescription claim for PsO treatment excluding topical steroids was 81.1% but higher (82.5%) when ≥1 diagnosis was from a dermatologist. Among 411 PsO patients with adequate information on PsO disease activity in EHRs, 1.5-5.8% had no disease activity, 31.3-36.8% mild, and 26.9-35.1% moderate-to-severe across the algorithms., Conclusions: Claims-based algorithms based on a combination of PsO diagnosis codes and dispensing for PsO-specific treatments had a moderate-to-high PPV. These algorithms can serve as a useful tool to identify patients with PsO in future real-world data pharmacoepidemiologic studies., (© 2021 John Wiley & Sons Ltd.)

Background/aims: This study was performed to undertake cross-cultural adaptation and validation of the Educational Needs Assessment Tool (ENAT) in rheumatoid arthritis (RA) for use in Korea., Methods: The study involved two main phases: cross-cultural adaptation of the ENAT from English into Korean, and validation of the Korean ENAT. The first phase followed the established process of cross-cultural adaptation of self-report measures, and in the second phase, the Korean ENAT data were analyzed using the Rasch measurement model. Fit to the model was determined using the observed data infit and outfit statistics. Additional tests of validity included unidimensionality and internal consistency., Results: Adequate conceptual equivalence was achieved following the adaptation process. A total of 123 patients completed the Korean ENAT. The mean age was 46.7 ± 12.3 years and the majority of patients (81.3%) were female. Thirty-five of the 39 items gave good fit to the model. The four items deviating from the model had infit and outfit > 1.50. The item separation index (5.26) and item reliability index (0.97) provided evidence for good reliability of items. All seven domains of the Korean ENAT fit the Rasch model. The internal consistency of the Korean ENAT was high, and unidimensionality was confirmed (person separation index, 3.41; reliability index, 0.92; item separation index, 16.82; reliability index, 1.00)., Conclusion: Using the standard procedure for cross-cultural adaptation, the ENAT has been adapted into Korean, and Rasch analysis has confirmed the construct validity, reliability, and unidimensionality of the Korean ENAT.

Objectives: To compare healthcare utilization and medical costs between patients with seronegative (SN) and seropositive (SP) rheumatoid arthritis (RA)., Methods: We conducted a nationwide population study using the Korean health insurance claims database in 2016. We divided patients with RA into SN and SP groups and compared healthcare utilization including medications, medical utilization, and direct medical costs for 1 year between the groups in a cross-sectional analysis. Differences in costs between patients with SPRA and SNRA were assessed using the quantile regression model. We performed longitudinal analysis using data from 2012 and 2016 to examine changes over time., Results: A total of 103,815 SPRA and 75,809 SNRA patients were included in the analyses. The SPRA group used significantly more methotrexate (73.2% versus 30.3%) and biologic agents (7.9% versus 2.9%) than the SNRA group. The number of RA-related outpatient visits [6.0 ± 3.7 versus 4.4 ± 4.0 times/year, standardized difference (SD) = 0.41] and annual medical costs per patient ($1027 versus $450/year, SD = 0.25) were higher in the SPRA group than the SNRA group. Quantile regression results indicated that the incremental cost of seropositivity on total medical costs of RA patients gradually increased as medical costs approached the upper quantile. The annual direct medical costs for each patient between 2012 and 2016 increased in both groups: by 25.1% in the SPRA group and 37.6% in the SNRA group., Conclusion: Annual RA-related direct medical costs and RA-related healthcare utilization per patient are higher in patients with SPRA than those with SNRA., Competing Interests: Conflict of interest statement: YKS has received research grants from Bristol-Myers Squibb, Eisai, Pfizer, and JW Pharmaceutical. HK, SKC, SC, SGI, SYJ, and EJJ have nothing to declare., (© The Author(s), 2021.)

Glucocorticoids are used to treat many autoimmune and inflammatory diseases. However, an adverse systemic effect is a deleterious effect on bone, which may lead to glucocorticoid-induced osteoporosis, characterized by a rapid and transient increase in bone resorption and fracture risk, which may increase rapidly within 3 months of commencing oral glucocorticoids. Therefore, early risk assessment and intervention are crucial for preventing fractures in patients receiving glucocorticoids. Recent practice guidelines recommend an assessment for fracture risk in patients beginning or receiving glucocorticoids for more than 3 months, and they have suggested fracture risk assessment tool values for identifying patients who need preventive treatment. Bisphosphonates are currently the recommended first-line therapy for the prevention and treatment of glucocorticoid-induced osteoporosis. These have been shown to increase the bone mineral density in the spine and hip and to decrease the incidence of vertebral fractures. Recently, a more potent antiresorptive agent, denosumab, has been shown to increase the bone density in patients receiving glucocorticoids. Teriparatide has been shown to have a preventive effect on vertebral fractures, but not on nonvertebral fractures. In this article we aimed to provide an update on glucocorticoid-induced osteoporosis by focusing on the assessment of its risk and treatment options.

Background: We aimed to examine the uptake of infliximab and etanercept biosimilars in patients with rheumatoid arthritis (RA) and its economic implication for healthcare expenditure., Methods: Using Korean Health Insurance Review and Assessment Service National Patient Samples, we extracted RA patients who used biologic disease modifying anti-rheumatic drugs (bDMARDs) between 2009 and 2018. Descriptive statistics were used to explain the basic features of the data. We calculated the proportion of users of each bDMARD among total patients with bDMARDs half-yearly. We assessed changes in the utilization proportions of bDMARDs including 4 tumor necrosis factor inhibitors (TNFis) and 2 non-TNFis, which have been approved for RA in Korea: etanercept, infliximab, adalimumab, golimumab, tocilizumab, and abatacept, and analyzed the changes in market share of biosimilars among the bDMARDs after their introduction. Overall trends of medical costs for each bDMARD were presented over the 10-year period., Results: Since the introduction of the biosimilar TNFis in 2012, the proportion of their use among bDMARDs steadily increased to 15.8% in 2018. While there has been a gradual increase in the use of biosimilar TNFis, the use of the corresponding originators has been decreasing. The introduction of biosimilar TNFis has resulted in a decrease in the medical costs of patients using either originator or biosimilar TNFis., Conclusion: In Korea, the proportional use of biosimilar TNFis has gradually increased since their introduction. The availability of less expensive biosimilar TNFis seems to have brought about a decrease in the medical costs of users of the originators., Competing Interests: Yoon-Kyoung Sung has received research grants from Bristol-Myers Squibb, Eisai, Pfizer, and JW Pharmaceutical. Soo-Kyung Cho, Sun-Young Jung, Hyoungyoung Kim, Yeo-Jin Song, and Kyungeun Lee have nothing to declare., (© 2021 The Korean Academy of Medical Sciences.)

Background: Patients with rheumatoid arthritis (RA) undergoing targeted therapy have a higher risk of developing tuberculosis (TB). This requires diagnosis and treatment of latent tuberculosis infection (LTBI). We aimed to evaluate whether diagnosis and treatment of LTBI in RA are effective in Korea, and to estimate the risk of TB development by calculating the incidence rate of active TB among RA patients receiving targeted therapy., Methods: We analyzed data from two prospective cohort studies of RA patients who received biologic disease-modifying antirheumatic drugs (bDMARDs) or Janus kinase (JAK) inhibitor. We selected new starters of targeted therapy and classified them into three groups receiving tumor necrosis factor (TNF) inhibitor, non-TNF inhibitor, and JAK inhibitor, respectively. We then compared LTBI prevalence, treatments, and active TB incidence during first-line therapy in each group., Results: A total of 765 RA patients (574 TNF inhibitor users, 132 non-TNF inhibitor users, and 59 JAK inhibitor users) were included in this study. Observation periods were 1,255.2 person-years (PYs), 264.7 PYs, and 53.3 PYs, respectively. All 765 patients underwent LTBI screening, and the positivity rate was 26.5% (n = 203). Of the 203 LTBI-positive patients, 189 (93.1%) received treatment. Only one patient, who was in the TNF inhibitor group, and was negative for the interferon gamma release assay (IGRA), did not receive LTBI treatment and developed active TB during follow-up., Conclusion: Although the prevalence of LTBI in RA patients who started targeted therapy was slightly elevated, the Korean guidelines specifying LTBI screening and treatment were effective in preventing latent TB from becoming active., Competing Interests: DHY received research grants from Celltrion and HR, and is on the speakers bureau of Celltrion and Celltrion Healthcare. YKS received research grants from Bristol-Myers Squibb, Eisai, Pfizer, and JW Pharmaceutical. YJS, SKC, HK, HWK, EN, and SCB have no disclosures to declare. All authors declare no conflict of interest associated with this work., (© 2021 The Korean Academy of Medical Sciences.)