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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.

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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]

ABSTRACT 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. [ABSTRACT FROM AUTHOR]

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).)

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.)

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.)

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.

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.)

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.