Jung-Yoon Choe

Sung Hae Chang, M.D., Ph.D., M.P.H., Gregory C. McDermott, M.D., M.P.H., Yeon-Ah Lee, M.D., Ph.D., Eun Ha Kang, M.D., Ph.D., M.P.H., Yong-Beom Park, M.D., Ph.D., Jung-Yoon Choe, M.D., Ph.D., Eun Young Lee, M.D., Ph.D., Jeffrey A. Sparks, M.D., M.M.S.c.. J Rheum Dis -0001;0:. https://doi.org/10.4078/jrd.2025.0161

Ji-Won Kim, M.D., Ph.D., Jun Sik Yoon, M.D., Ph.D., Sojeong Park, M.P.H., Hasung Kim, M.P.H., Bo Young Kim, M.D., Hwajeong Lee, M.D., Ph.D., Sung-Hoon Park, M.D., Ph.D., Seong-Kyu Kim, M.D., Ph.D., Jung-Yoon Choe, M.D., Ph.D.. J Rheum Dis -0001;0:. https://doi.org/10.4078/jrd.2025.0070

Bo Young Kim, M.D., Ji-Won Kim, M.D., Ph.D., Hwajeong Lee, M.D., Ph.D., Sung-Hoon Park, M.D., Ph.D., Seong-Kyu Kim, M.D., Ph.D., Jung-Yoon Choe, M.D., Ph.D.. J Rheum Dis 2025;32:252-63. https://doi.org/10.4078/jrd.2025.0039

Objective: To investigate baseline and change of pulmonary damage biomarkers (serum Krebs von den Lungen 6 [KL-6], human surfactant protein D [hSP-D], and matrix metalloproteinase 7 [MMP-7]) with rheumatoid arthritis–associated interstitial lung disease (RA-ILD) progression.Methods: In the Korean Rheumatoid Arthritis Interstitial Lung Disease (KORAIL) cohort, a prospective cohort, we enrolled patients with RA and ILD confirmed by chest computed tomography imaging and followed annually. ILD progression was defined as worsening in physiological and radiological domains of the 2022 American Thoracic Society, European Respiratory Society, Japanese Respiratory Society, and Latin American Thoracic Society guideline for progressive pulmonary fibrosis (PPF). Associations between biomarkers and RA-ILD progression were analyzed using multivariable Cox regression, adjusting for potential confounders.Results: We analyzed 136 patients with RA-ILD (mean age 66.5 yrs, 30% male, 60.3% with usual interstitial pneumonia pattern). During a median 3.0 years of follow-up, 47 patients (34.6%) experienced progression. Higher baseline KL-6 and hSP-D levels were associated with higher risk of ILD progression (multivariable hazard ratios [HRs] 1.37 [95% CI 1.03-1.82] and 1.51 [95% CI 1.09-2.08], respectively), whereas only the highest quartile of MMP-7 showed an increased risk (multivariable HR 2.60 [95% CI 1.07-6.33]). Increasing levels of serum KL-6 at 1 year showed the strongest association with progression (ΔKL-6: multivariable HR 2.00 [95% CI 1.29-3.11]), additionally adjusting for baseline biomarker levels.Conclusion: In this first prospective study to apply PPF criteria to RA-ILD, 34.6% progressed over 3 years. Higher baseline KL-6 and hSP-D were associated with progression. In follow-up, greater change in KL-6 was associated with progression. Serial measurement of pulmonary damage biomarkers may predict RA-ILD progression and may be helpful in monitoring patients and treatment decisions.

Introduction: Biosimilars are increasing selected as a cost-effective treatment option in the management of immune-mediated inflammatory diseases. Despite equivalent efficacy of biosimilars was demonstrated compared with the originators in randomized controlled trials, biosimilar uptake is often impacted by lack of confidence in these products by the patients. The Patient Reported Outcomes for SB5, an adalimumab biosIMILAR, in patients with rheumatoid arthritis (RA) and ankylosing spondylitis (AS) (PRO-SIMILAR) study was designed to evaluate the efficacy of SB5, from the perspectives of the patients in real world settings. Methods and analysis: PRO-SIMILAR is an ongoing phase IV, single-arm, open-label trial conducted in 35 hospitals across Korea. The study is designed for 1000 adult patients with RA and AS (at least ≥300 in each group) treated in routine clinical practice. Participants are treated with SB-5 40 mg every other week for 52 weeks. The primary efficacy endpoint is European quality of life-5 dimensions-5 level index score at week 52 compared to baseline. The secondary efficacy endpoints are changes in disease activity index scores, proportion of patients achieving remission and clinical response, and rate of SB5 persistence. The safety and exploratory endpoints are include assessments of adverse events, immunogenicity, and pen/syringe preference. Data are collected at baseline, 12, 24 (for RA), 36 (for AS), and 52 weeks.

Objective: Chondrocyte apoptosis has been considered a crucial mechanism that is responsible for cartilage destruction in osteoarthritis (OA). The mechanism of interleukin-37 (IL-37) on chondrocyte apoptosis has not been clearly determined in the pathogenesis of OA. Here, we explored the role of IL-37 in the regulation of cellular apoptosis in rat chondrocytes stimulated by IL-1β. Methods: Rat chondrocytes were used in in vitro study, and were stimulated with IL-1β (10 ng/mL) and/or recombinant IL-37 (rIL-37; 100 ng/mL) after cytotoxicity assessments using these cytokines were conducted. After rIL-37 treatment of chondrocytes stimulated with IL-1β, the cell proliferation assay, apoptosis assays, including expression of mitochondrial apoptosis-related markers, flow cytometry analysis of annexin V-FITC/propidium iodide (PI), cell cycle analysis, and Hoechst 33342 staining, and reactive oxygen species (ROS) measurement were used. Results: IL-1β induced expression of inflammatory cytokines and triggered degradation of the extracellular matrix of rat chondrocytes, but this effect was significantly attenuated by rIL-37 treatment. Enhanced ROS generation following IL-1β stimulation was reduced in a dose-dependent manner after stimulation with rIL-37. IL-1β induced pro-apoptotic markers and suppressed anti-apoptotic markers in rat chondrocytes. Flow cytometry using annexin V-FITC/PI revealed that IL-1β increased the apoptosis rate of rat chondrocytes, and that this effect was markedly reversed by treatment with rIL-37. Conclusions: IL-37 potently attenuated IL-1β-mediated apoptosis of rat chondrocytes by blocking ROS production. This study suggests that IL-37 can serve as a novel anti-cytokine therapy in OA by blocking chondrocyte apoptosis.

Objective: The pleiotropic effect of hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) is responsible for potent defense against inflammatory response. This study evaluated the inhibitory effects of HMG-CoA reductase inhibitors on the monosodium urate (MSU)-induced inflammatory response through the regulation of interleukin-37 (IL-37) expression. Methods: Serum was collected from patients with gout (n = 40) and from healthy controls (n = 30). The mRNA and protein expression of the target molecules IL-1β, IL-37, caspase-1, and Smad3 were measured in THP-1 macrophages stimulated with MSU, atorvastatin, or rosuvastatin using a real-time quantitative polymerase chain reaction and Western blot assay. Transfection with IL-1β or Smad3 siRNA in THP-1 macrophages was used to verify the pharmaceutical effect of statins in uric-acid-induced inflammation. Results: Serum IL-37 levels in gout patients were significantly higher than in controls (p < 0.001) and was associated with the serum uric acid level (r = 0.382, p = 0.008). THP-1 cells stimulated with MSU markedly induced IL-37 mRNA expression and the transition of IL-37 from the cytoplasm to the nucleus. Recombinant IL-37 treatment dose-dependently inhibited activation of caspase-1 and IL-1β in MSU-induced inflammation. Atorvastatin and rosuvastatin attenuated caspase-1 activation and mature IL-1β expression but augmented translocation of IL-37 from the cytoplasm to the nucleus. Atorvastatin and rosuvastatin induced phosphorylation of Smad3 in THP-1 cells treated with MSU crystals. Statins potently attenuated translocation of IL-37 from the cytoplasm to the nucleus in THP-1 macrophages transfected with Smad3 siRNA compared to cells with negative control siRNA. Conclusions: This study revealed that statins inhibit the MSU-induced inflammatory response through phosphorylated Smad3-mediated IL-37 expression in THP-1 macrophages.

Objective To investigate the risk of cardiovascular disease (CVD) associated with increasing dose of a non-steroidal anti-inflammatory drug (NSAID) in patients with ankylosing spondylitis (AS). Methods Using the Korean National Health Insurance database, patients newly diagnosed with AS without prior CVD between 2010 and 2018 were included in this nationwide cohort study. The primary outcome was CVD, a composite outcome of ischaemic heart disease, stroke or congestive heart failure. Exposure to NSAIDs was evaluated using a time-varying approach. The dose of NSAIDs was considered in each exposure period. Cox proportional hazard regression was used to investigate the risk of CVD associated with NSAID use. Results Of the 19 775 patients (mean age, 36 years; 75% were male), 19 706 received NSAID treatment. During follow-up period of 98 290 person-years, 1663 cases of CVD occurred including 1157 cases of ischaemic heart disease, 301 cases of stroke and 613 cases of congestive heart failure. Increasing dose of NSAIDs was associated with incident CVD after adjusting for confounders (adjusted HR (aHR) 1.10; 95% CI 1.08 to 1.13). Specifically, increasing dose of NSAIDs was associated with incident ischaemic heart disease (aHR 1.08; 95% CI 1.05 to 1.11), stroke (aHR 1.09; 95% CI 1.04 to 1.15) and congestive heart failure (aHR 1.12; 95% CI 1.08 to 1.16). The association between NSAID dose and higher CVD risk was consistent in different subgroups. Conclusion In a real-world AS cohort, higher dose of NSAID treatment was associated with a higher risk of CVD, including ischaemic heart disease, stroke and congestive heart failure.

Min Wook So, M.D., Ph.D., Sang-Hyon Kim, M.D., Ph.D., Dong Wook Kim, M.D., Ph.D., Yoon-Kyoung Sung, M.D., Ph.D., MPH, Jung-Yoon Choe, M.D., Ph.D., Sang-Il Lee, M.D., Ph.D., Jin-Wuk Hur, M.D., Ph.D., Hye-Soon Lee, M.D., Ph.D., Sang-Heon Lee, M.D., Ph.D., Jin Ran Kim, PharmD. J Rheum Dis 2024;31:86-96. https://doi.org/10.4078/jrd.2023.0045

Objective: The pleiotropic effect of hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) is responsible for potent defense against inflammatory response. This study evaluated the inhibitory effects of HMG-CoA reductase inhibitors on monosodium urate (MSU)-induced inflammatory response through the regulation of interleukin-37 (IL-37) expression. Methods: Serum was collected from patients with gout (n = 40) and from healthy controls (n = 30). The mRNA and protein expression of target molecules IL-1b, IL-37, caspase-1, and Smad3 was measured in THP-1 cells stimulated with MSU, atorvastatin, or rosuvastatin using real-time quantitative polymerase chain reaction and Western blot assay. Transfection with IL-1b or Smad3 siRNA in THP-1 cells was used to verify the pharmaceutical effect of statins in uric acid-induced inflammation. Results: Serum IL-37 level in gout patients was significantly higher than in controls (p < 0.001) and was associated with serum uric acid level (r = 0.382, p = 0.008). THP-1 cells stimulated with MSU markedly induced IL-37 mRNA expression and transition of IL-37 from cytoplasm to nucleus. Recombinant IL-37 treatment dose-dependently inhibited activation of caspase-1 and IL-1b in MSU-induced inflammation. Atorvastatin and rosuvastatin attenuated caspase-1 activation and mature IL-1b expression but augmented translocation of IL-37 from cytoplasm to nucleus. Atorvastatin and rosuvastatin induced phosphorylation of Smad3 in THP-1 cells treated with MSU crystals. Statins potently attenuated translocation of IL-37 from cytoplasm to nucleus in THP-1 cells transfected with Smad3 siRNA compared to cells with negative control siRNA. Conclusion: This study revealed that statins inhibit MSU-induced inflammatory response through augmentation of phosphorylated Smad3-mediated IL-37 expression in THP-1 cells.