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1.
Yonsei Medical Journal ; : 697-704, 2023.
Article in English | WPRIM | ID: wpr-1003221

ABSTRACT

Purpose@#To assess the drug retention rate of interleukin-17 inhibitors (IL-17is) over long-term observation in patients with axial spondyloarthritis (axSpA) in whom treatment with tumor necrosis factor inhibitors (TNFis) failed and to determine baseline factors associated with discontinuation of IL-17is. @*Materials and Methods@#This retrospective cohort study included 68 patients with axSpA started on IL-17is after an inadequate response or intolerance to ≥1 TNFis. Drug retention rates at 1, 2, and 3 years were assessed. Baseline (i.e., at initiation of IL-17is) factors associated with discontinuation of IL-17is were evaluated using multivariable Cox proportional hazard regression analysis. @*Results@#Over 1933.9 person-months of observation in 68 patients, discontinuation of IL-17is occurred in 27 (39.7%) patients. Twenty (29.4%) patients discontinued IL-17is because of ineffectiveness, and 7 (10.3%) patients discontinued IL-17is because of adverse events. The 1-year, 2-year, and 3-year drug retention rates for IL-17is were 71.9%, 66.5%, and 62.0%, respectively. Current smoking was associated with a higher risk of IL-17is discontinuation [adjusted hazard ratio (HR)=2.256, 95% confidence interval (CI)=1.053–4.831, p=0.036], while previous use of ≥3 TNFis (vs. 1) was significantly associated with a lower risk of IL-17is discontinuation (adjusted HR=0.223, 95% CI=0.051–0.969, p=0.045). @*Conclusion@#In patients with axSpA in whom TNFis failed, the long-term drug retention rate of IL-17is appears to be acceptable, with a 3-year drug retention rate of approximately 60%. Current smoking was associated with a higher risk of discontinuing IL-17is, whereas previous use of ≥3 TNFis was associated with a lower risk of discontinuing IL-17is.

2.
The Korean Journal of Internal Medicine ; : 620-640, 2023.
Article in English | WPRIM | ID: wpr-1003066

ABSTRACT

We aimed to develop evidence-based recommendations for treating axial spondylarthritis (axSpA) in Korea. The development committee was constructed, key clinical questions were determined, and the evidence was searched through online databases including MEDLINE, Embase, Cochrane, KoreaMed, and Kmbase. Systematic literature reviews were conducted, quality of evidence was determined, and draft recommendations were formulated according to the Grading of Recommendations Assessment, Development, and Evaluations methodology. Recommendations that reached 80% consensus among a voting panel were finalized. Three principles and 21 recommendations were determined. Recommendations 1 and 2 pertain to treatment strategies, regular disease status assessment, and rheumatologist-steered multidisciplinary management. Recommendations 3 and 4 strongly recommend patient education, exercise, and smoking cessation. Recommendations 5–12 address pharmacological treatment of active disease using nonsteroidal anti-inflammatory drugs, glucocorticoids, sulfasalazine, biologics, and Janus kinase inhibitors. Recommendations 13–16 address treatment in stable disease. We suggest against spa and acupuncture as therapies (Recommendation 17). Recommendations 18 and 19 pertain to total hip arthroplasty and spinal surgery. Monitoring of comorbidities and drug toxicities are recommended (Recommendations 20 and 21). Recommendations for axSpA treatment in a Korean context were developed based on comprehensive clinical questions and evidence. These are intended to guide best practice in the treatment of axSpA.

3.
Journal of Rheumatic Diseases ; : 151-169, 2023.
Article in English | WPRIM | ID: wpr-1001531

ABSTRACT

We aimed to develop evidence-based recommendations for treating axial spondylarthritis (axSpA) in Korea. The development committee was constructed, key clinical questions were determined, and the evidence was searched through online databases including MEDLINE, Embase, Cochrane, KoreaMed, and KMbase. Systematic literature reviews were conducted, quality of evidence was determined, and draft recommendations were formulated according to the Grading of Recommendations Assessment, Development, and Evaluations methodology. Recommendations that reached 80% consensus among a voting panel were finalized. Three principles and 21 recommendations were determined. Recommendations 1 and 2 pertain to treatment strategies, regular disease status assessment, and rheumatologist-steered multidisciplinary management. Recommendations 3 and 4 strongly recommend patient education, exercise, and smoking cessation. Recommendations 5~12 address pharmacological treatment of active disease using nonsteroidal anti-inflammatory drugs, glucocorticoids, sulfasalazine, biologics, and Janus kinase inhibitors.Recommendations 13~16 address treatment in stable disease. We suggest against spa and acupuncture as therapies (Recommendation 17). Recommendations 18 and 19 pertain to total hip arthroplasty and spinal surgery. Monitoring of comorbidities and drug toxicities are recommended (Recommendations 20 and 21). Recommendations for axSpA treatment in a Korean context were developed based on comprehensive clinical questions and evidence. These are intended to guide best practice in the treatment of axSpA.

4.
The Korean Journal of Internal Medicine ; : 546-556, 2023.
Article in English | WPRIM | ID: wpr-977372

ABSTRACT

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. @*Conclusions@#Our interim findings reveal JAKi have comparable effectiveness and safety to bDMARDs at 24 weeks after treatment initiation.

5.
Yonsei Medical Journal ; : 241-251, 2022.
Article in English | WPRIM | ID: wpr-927157

ABSTRACT

Purpose@#Here, we aimed to elucidate the differences in microbiota composition between patients with gout and those with asymptomatic hyperuricemia (asHU) and determine the effect of uric acid-lowering therapy (ULT) on the gut microbiome. @*Materials and Methods@#Stool samples from patients with asHU (n=8) and three groups of gout patients, i.e., acute gout patients before ULT (0ULT, n=14), the same acute gout patients after 30-day ULT (30ULT, n=9), and chronic gout patients after ≥6-month ULT (cULT, n=18) were collected and analyzed using 16S rRNA gene-based pyrosequencing. The composition of microbial taxonomy and communities, species diversity, and relationships among microbial communities were elucidated by bioinformatic analysis. @*Results@#Gout patients showed less diverse gut microbiota than asHU patients. The microbiota of the asHU group exhibited a higher Firmicutes-to-Bacteroidetes (F/B) ratio and lower Prevotella-to-Bacteroides (P/B) ratio than the gout group; significantly, the F/B ratio increased in gout patients after ULT. Moreover, a balanced enterotype populated asHU patients compared to gout patients. Notably, the gut microbiota in asHU patients had a higher proportion of taxa with potentially anti-inflammatory effects compared to the gut microbiota in gout patients. @*Conclusion@#We found that microbial composition differs between asHU and gout patients. The differential gut microbiota in asHU patients may protect against gout development, whereas that in gout patients may have a role in gout provocation. ULT in gout patients altered the gut microbiota, and may help alleviate gout pathology and mitigate gout progression.

6.
Yonsei Medical Journal ; : 814-821, 2021.
Article in English | WPRIM | ID: wpr-904301

ABSTRACT

Purpose@#To evaluate whether vascular uptake on 18 F-fluorodeoxyglucose positron emission tomography/computed tomography ( 18F-FDG PET/CT) during the clinically inactive state of Takayasu arteritis (TAK) is associated with disease relapse. @*Materials and Methods@#Patients with TAK who underwent 18F-FDG PET/CT during the clinically inactive state of the disease between 2006 and 2019 were included. Clinically inactive disease was defined as a status not fulfilling the National Institutes of Health (NIH) criteria for active disease in TAK. Relapse was defined as recurrence of clinically active disease after a clinically inactive period, requiring change in the treatment regimen. Vascular uptake on 18F-FDG PET/CT was assessed using target/background ratio (TBR), calculated as arterial maximum standardized uptake value (SUV)/mean SUV in venous blood pool. Multivariable Cox regression analysis was performed to identify factors associated with relapse. @*Results@#A total of 33 patients with clinically inactive TAK were included. During a median observation period of 4.5 (0.9–8.1) years, relapse occurred in 9 (27.3%) patients at median 1.3 (0.7–6.9) years. Notably, TBR [1.5 (1.3–1.8) vs. 1.3 (1.1–1.4), p=0.044] was significantly higher in patients who relapsed than in those who did not. On multivariable Cox regression analysis, the presence of NIH criterion 2 [adjusted hazard ratio (HR): 7.044 (1.424–34.855), p=0.017] and TBR [adjusted HR: 11.533 (1.053–126.282), p=0.045] were significantly associated with an increased risk of relapse. @*Conclusion@#Vascular uptake on 18F-FDG PET/CT and the presence of NIH criterion 2 are associated with future relapse in patients with clinically inactive TAK.

7.
Yonsei Medical Journal ; : 814-821, 2021.
Article in English | WPRIM | ID: wpr-896597

ABSTRACT

Purpose@#To evaluate whether vascular uptake on 18 F-fluorodeoxyglucose positron emission tomography/computed tomography ( 18F-FDG PET/CT) during the clinically inactive state of Takayasu arteritis (TAK) is associated with disease relapse. @*Materials and Methods@#Patients with TAK who underwent 18F-FDG PET/CT during the clinically inactive state of the disease between 2006 and 2019 were included. Clinically inactive disease was defined as a status not fulfilling the National Institutes of Health (NIH) criteria for active disease in TAK. Relapse was defined as recurrence of clinically active disease after a clinically inactive period, requiring change in the treatment regimen. Vascular uptake on 18F-FDG PET/CT was assessed using target/background ratio (TBR), calculated as arterial maximum standardized uptake value (SUV)/mean SUV in venous blood pool. Multivariable Cox regression analysis was performed to identify factors associated with relapse. @*Results@#A total of 33 patients with clinically inactive TAK were included. During a median observation period of 4.5 (0.9–8.1) years, relapse occurred in 9 (27.3%) patients at median 1.3 (0.7–6.9) years. Notably, TBR [1.5 (1.3–1.8) vs. 1.3 (1.1–1.4), p=0.044] was significantly higher in patients who relapsed than in those who did not. On multivariable Cox regression analysis, the presence of NIH criterion 2 [adjusted hazard ratio (HR): 7.044 (1.424–34.855), p=0.017] and TBR [adjusted HR: 11.533 (1.053–126.282), p=0.045] were significantly associated with an increased risk of relapse. @*Conclusion@#Vascular uptake on 18F-FDG PET/CT and the presence of NIH criterion 2 are associated with future relapse in patients with clinically inactive TAK.

8.
Journal of Rheumatic Diseases ; : 1-3, 2020.
Article in English | WPRIM | ID: wpr-786148

ABSTRACT

No abstract available.


Subject(s)
Propensity Score , Uveitis, Anterior
9.
Yonsei Medical Journal ; : 951-957, 2020.
Article | WPRIM | ID: wpr-833385

ABSTRACT

Purpose@#To compare the clinical characteristics and renal outcomes between patients who initially had lupus nephritis (LN) at the onset of systemic lupus erythematosus (SLE) (initial-onset LN) and those who developed LN within 5 years after SLE onset (early-onset LN). @*Materials and Methods@#SLE patients with biopsy-proven LN were retrospectively reviewed. The clinical parameters and renal outcomes were compared between initial-onset and early-onset LN groups. We used Cox regression analysis to estimate risk of worse renal outcomes according to the onset time of LN. @*Results@#Of all 136 LN patients, 92 (67.6%) and 44 (32.4%) patients were classified into the initial-onset and early-onset LN groups, respectively. The initial-onset LN group had higher prevalences of class IV LN (54.3% vs. 34.1%, ,p=0.027), impaired renal function (34.8% vs. 11.4%, p=0.004), microscopic hematuria (73.9% vs. 54.5%, p=0.024), and higher urine protein/creatinine ratio [4626.1 (2180.0–6788.3) mg/g vs. 2410.0 (1265.0–5168.5) mg/g,p=0.006] at LN diagnosis. Renal relapse (46.3% vs. 25.7%, p=0.039) and progression to chronic kidney disease (CKD) or end-stage renal disease (ESRD) were more common (24.4% vs. 8.3%, p=0.042) in the initial-onset LN group. In Cox regression analysis, the initial-onset LN group had higher risks of renal relapse [adjusted hazard ratio (HR) 3.56, 95% confidence interval (CI) 1.51–8.35,p=0.004] and progression to CKD or ESRD (adjusted HR 4.57, 95% CI 1.03–20.17,p=0.045), compared with the early-onset LN group. @*Conclusion@#Patients with LN at SLE onset may have more severe renal presentations and experience worse renal outcomes than those who develop LN within 5 years.

10.
Journal of Rheumatic Diseases ; : 41-45, 2019.
Article in English | WPRIM | ID: wpr-719462

ABSTRACT

OBJECTIVE: To evaluate the fate of abstracts presented at scientific meetings of the Korean College of Rheumatology (KCR). METHODS: This study examined the abstracts presented at annual meetings of the KCR from 2005 to 2014. Only original studies were selected, excluding case reports. A manual search was conducted using PubMed, KoreaMed, Cochrane Library, and Embase to track the published articles. The abstracts were considered to have been published if the authors, title, study design, and results were the same for a published article. In addition, they were considered published if the author and the study design matched, even if the results of the abstract and the results of the published articles were not identical. RESULTS: A total of 928 abstracts from 2005 to 2014 were analyzed. Of the 928 abstracts, 468 (50.43%) abstracts were published in a peer-reviewed journal and the mean time to publication was 19 months. Of the 468 abstracts, 414 were published in a science citation index extended (SCI[E]) journal, and 54 were published in non-SCI(E) journals. The proportion of SCI(E) articles increased annually. The average impact factor for the SCI(E) journals was 2.93. In subgroup analysis, the abstracts that were awarded the best oral or best poster presentation were more likely to be published as full-length articles with a higher impact factor than the abstracts not awarded. CONCLUSION: Half of the abstracts presented in the KCR annual meetings were published in a peer-reviewed journal. Approximately 90% of the articles were published in a SCI(E) journal.


Subject(s)
Awards and Prizes , Korea , Publications , Rheumatology
11.
The Korean Journal of Internal Medicine ; : 1224-1233, 2018.
Article in English | WPRIM | ID: wpr-718009

ABSTRACT

BACKGROUND/AIMS: The objective of this study was to determine the efficacy and safety of add-on therapy with certolizumab pegol (CZP) in active rheumatoid arthritis (RA) patients of a single ethnicity. METHODS: In this 24-week, phase 3, randomized, double-blind, placebo-controlled trial, eligible patients (n = 127) were randomized 2:1 to subcutaneous CZP + methotrexate (MTX; 400 mg at week 0, 2, and 4 followed by 200 mg every 2 weeks) or placebo + MTX. RESULTS: At week 24, the American College of Rheumatology criteria for 20% (ACR20) response rate was significantly greater with CZP + MTX than with placebo (66.7% vs. 27.5%, p < 0.001). Differences in ACR20 response rates for CZP vs. placebo were significant from week 1 (p < 0.05) and remained significant through week 24. The CZP group reported significant improvement in physical function and disability compared to the placebo group (p < 0.001) at week 24, as assessed by Korean Health Assessment Questionnaire-Disability Index (KHAQ-DI). Post hoc analysis indicated that the proportion of patients who had ACR70 responses, Disease Activity Score 28 (DAS28) low disease activity, and DAS28 remission at week 24 was greater in CZP + MTX-treated patients who achieved a decrease in DAS28 ≥ 1.2 (43.8%) at week 4 than in nonresponders. Among 18 (22.2%) and 14 patients (35.0%) in CZP and placebo groups who had latent tuberculosis (TB), none developed active TB. Most adverse events were mild or moderate. CONCLUSIONS: CZP treatment combined with MTX in active RA patients with moderate to severe disease activity and an inadequate response to MTX resulted in rapid onset of efficacy, which is associated with better clinical outcome at week 24 and has an acceptable safety profile, especially in an intermediate TB-burden population.


Subject(s)
Humans , Arthritis, Rheumatoid , Certolizumab Pegol , Latent Tuberculosis , Methotrexate , Rheumatology
12.
Journal of Rheumatic Diseases ; : 227-235, 2017.
Article in English | WPRIM | ID: wpr-31831

ABSTRACT

OBJECTIVE: Failure of first-line anti-tumor necrosis factor (TNF) agents in in rheumatoid arthritis patients leads to decisions among second-line biologic agents. To better inform these decisions, the therapeutic effectiveness of rituximab is compared with other second-line biologic agents in this observational study. METHODS: Between November 2011 and December 2014, study subjects were observed for 12 month periods. Patients with an inadequate response to initial anti-TNF agent received either rituximab or alternative anti-TNF agents (adalimumab/etanercept/infliximab) based on the preference of patients and physicians. The efficacy end point of this study was the change in 28-joint count Disease Activity Score (DAS28) at six and 12 months from baseline. Safety data were also collected. RESULTS: Ninety patients were enrolled in the study. DAS28 at six months did not change significantly whether the patients were treated with rituximab or alternative anti-TNF agents in intention-to-treat analysis (n=34, −1.63±0.30 vs. n=31, −2.05±0.34) and standard population set analysis (n=31, −1.51±0.29 vs. n=24, −2.21±0.34). Similarly, the change in DAS28 at 12 months did not reach statistical significance (−1.82±0.35 in the rituximab vs. −2.34±0.44 in the alternative anti-TNF agents, p=0.2390). Furthermore, the incidences of adverse events were similar between two groups (23.5% for rituximab group vs. 25.8% for alternative anti-TNF agents group, p=0.7851). CONCLUSION: Despite the limitations of our study, switching to rituximab or alternative anti-TNF agents after failure of the initial TNF antagonist showed no significant therapeutic difference in DAS28 reduction.


Subject(s)
Humans , Arthritis, Rheumatoid , Biological Factors , Biological Products , Incidence , Necrosis , Observational Study , Rituximab
13.
Journal of Rheumatic Diseases ; : 27-34, 2017.
Article in English | WPRIM | ID: wpr-160553

ABSTRACT

OBJECTIVE: This study was performed to assess the cost-effectiveness of cyclooxygenase-2 (COX2)-selective inhibitor, non-selective non-steroidal anti-inflammatory drugs (NSAIDs), and non-selective NSAID with proton pump inhibitors (PPIs) while considering upper and lower gastrointestinal (GI) safety in patients with rheumatoid arthritis (RA). METHODS: A Markov model was used to estimate the costs and effectiveness. Estimates of therapeutic efficacy and upper/lower GI safety were based on results from large randomized controlled trials. The main outcome measure was cost effectiveness, based on the quality-adjusted life years (QALYs) gained. Safety parameters included clinical upper GI symptoms, uncomplicated ulcer, upper GI bleeding, upper GI perforation, clinical lower GI symptoms, lower GI bleeding, and lower GI perforation. Cost data were obtained from patients treated in a tertiary referral center in Korea. RESULTS: The expected three year cost was 3,052,800 Korean won (KRW) for COX2-selective inhibitor, 3,170,800 KRW for nonselective NSAID, and 3,325,900 KRW for non-selective NSAID with PPI. QALYs were 2.87446, 2.85320, and 2.85815, respectively. The total cost for COX2-selective inhibitor use was lower than non-selective NSAID, but QALY was higher, indicating that the incremental cost effectiveness ratio of COX2-selective inhibitor is superior. CONCLUSION: COX2-selective inhibitor has reasonable cost-effectiveness adjusted for upper and lower GI toxicity for patients with RA in Korea.


Subject(s)
Humans , Arthritis, Rheumatoid , Cost-Benefit Analysis , Cyclooxygenase 2 , Hemorrhage , Korea , Outcome Assessment, Health Care , Proton Pump Inhibitors , Quality-Adjusted Life Years , Tertiary Care Centers , Ulcer
14.
Journal of Rheumatic Diseases ; : 337-339, 2016.
Article in English | WPRIM | ID: wpr-34294

ABSTRACT

No abstract available.


Subject(s)
Blood Platelets
15.
Korean Journal of Medicine ; : 739-744, 2011.
Article in Korean | WPRIM | ID: wpr-36752

ABSTRACT

Henoch-Schonlein purpura (HSP) is an immunologically mediated systemic vasculitis of small blood vessels that primarily involves the skin, gastrointestinal tract, joints, and kidneys. HSP is a relatively common vasculitic syndrome in children, which usually resolves within several weeks, and requires no treatment. The pulmonary parenchymal involvement of HSP is a rare complication that predominantly occurs in adolescents and adults. Mortality following HSP pulmonary presentation is extremely high. Here, we report a case of HSP combined with pulmonary hemorrhage as a presentation of the vasculitic involvement of the lung. Recently, we experienced a case of a 49-year-old male patient with HSP who presented with palpable purpura, enteritis, and glomerulonephritis. Following the diagnosis of HSP, the patient developed sudden pulmonary hemorrhage due to the pulmonary involvement of vasculitis, and recovered following glucocorticoid therapy.


Subject(s)
Adolescent , Adult , Child , Humans , Male , Middle Aged , Blood Vessels , Enteritis , Gastrointestinal Tract , Glomerulonephritis , Glucocorticoids , Hemorrhage , Joints , Kidney , Lung , Purpura , IgA Vasculitis , Skin , Systemic Vasculitis , Vasculitis
16.
Yonsei Medical Journal ; : 113-120, 2011.
Article in English | WPRIM | ID: wpr-146138

ABSTRACT

PURPOSE: This study was performed to determine whether the serum concentrations of interleukin (IL)-6 family cytokines are elevated in patients with rheumatoid arthritis (RA) and to investigate the relationship between IL-6 family cytokine levels and disease activity in RA patients. MATERIALS AND METHODS: We obtained serum samples from 40 patients with RA and 40 age- and sex-matched healthy controls, and we assessed the clinical parameters of disease activity, including the 28-joint disease activity score (DAS28) and C-reactive protein (CRP) levels. Serum samples from five patients with high disease activity (DAS28 > 5.1) were also collected at the eighth week of treatment. Serum concentrations of IL-6, IL-11, and leukemia inhibitory factor (LIF) were measured using an enzyme-linked immunosorbent assay (ELISA). RESULTS: Serum concentrations of IL-6 family cytokines, including IL-6, IL-11, and LIF, were significantly elevated in patients with RA compared to those of healthy controls. Although there was no significant relationship between IL-6 family cytokine levels and DAS28, the IL-6 levels of patients with RA showed a significant correlation with CRP levels. After eight weeks of medical treatment in patients with high disease activity, a decrease in DAS28 was associated with a significant decrease in the serum concentrations of IL-6 and IL-11. CONCLUSION: The serum concentrations of IL-6 family cytokines were significantly elevated in patients with RA, and they decreased with medical treatment. These findings suggest a possible role for IL-6 family cytokines in the pathogenesis of RA.


Subject(s)
Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Young Adult , Arthritis, Rheumatoid/blood , C-Reactive Protein/analysis , Cytokines/blood , Enzyme-Linked Immunosorbent Assay , Interleukin-11/blood , Interleukin-6/blood , Leukemia Inhibitory Factor/blood
18.
The Journal of the Korean Rheumatism Association ; : 153-161, 2010.
Article in Korean | WPRIM | ID: wpr-182265

ABSTRACT

OBJECTIVE: This study investigated the effect of rosiglitazone, a synthetic peroxisome proliferator-activated receptor-gamma (PPAR-gamma) agonist, on pro-inflammatory gene expressions and cellular proliferation of fibroblast like synoviocyte (FLS) from patients with rheumatoid arthritis (RA), and to determine whether these actions are mediated by nuclear factor-kappaB (NF-B) down-regulation. METHODS: Synovial tissues from patients with RA were obtained during total knee replacement surgery, and FLS were isolated. RA FLS were subsequently treated with 10 micrometer, 50 micrometer and 150 micrometer rosiglitazone with or without TNF-alpha (10 ng/mL) stimulation. FLS proliferation in response to rosiglitazone treatment was measured by MTT assay, and mRNA expressions of IL-1beta, IL-6, CCL-2, CCL-7, COX-2 and MMP-9 were determined by real-time quantitative RT-PCR. The effects of rosiglitazone on NF-kappaB activation were evaluated using electrophoretic mobility shift assay (EMSA). RESULTS: Rosiglitazone treatment without TNF-alpha induced a dose-dependent reduction in mRNA expressions of IL-1beta, IL-6, CCL-2, CCL-7, COX-2 and MMP-9 from RA FLS. When TNF-alpha were treated with rosiglitazone, mRNA expressions of COX-2, MMP-9 were reduced dose-dependently. But mRNA expressions of IL-1beta, IL-6, CCL-2, CCL-7 were increased in 10 micrometer rosiglitazone with TNF-alpha and then decreased as the concentration of rosiglitazone increased. Rosiglitazone treatment also suppressed FLS proliferation in a dose-dependent manner, and EMSA showed decreased NF-kappaB expression with rosiglitazone treatment. CONCLUSION: Rosiglitazone suppressed cellular proliferation and mRNA expressions of pro-inflammatory mediators by down-regulating the NF-kappaB signaling pathway in RA FLS. The outcomes suggest that activation of PPAR-gamma can be a novel therapeutic approach in RA.


Subject(s)
Humans , Arthritis, Rheumatoid , Arthroplasty, Replacement, Knee , Cell Proliferation , Down-Regulation , Electrophoretic Mobility Shift Assay , Fibroblasts , Gene Expression , Interleukin-6 , NF-kappa B , Peroxisomes , RNA, Messenger , Thiazolidinediones , Tumor Necrosis Factor-alpha
19.
The Journal of the Korean Rheumatism Association ; : 344-346, 2009.
Article in Korean | WPRIM | ID: wpr-187827

ABSTRACT

No abstract available.


Subject(s)
Osteitis Deformans , Skull
20.
Yonsei Medical Journal ; : 288-294, 2008.
Article in English | WPRIM | ID: wpr-30672

ABSTRACT

PURPOSE: To determine the levels of bone and cartilage turnover markers in men with ankylosing spondylitis (AS) and to investigate their associations with disease activity, bone mineral density, and radiographic damage of the spine. PATIENTS AND METHODS: This cross-sectional study enrolled 35 men with newly diagnosed AS. The bone mineral densities (BMD) of their lumbar spines and proximal femurs, Bath AS Disease Activity Index (BASDAI), and Bath AS Radiographic Index (BASRI) were evaluated. Urinary C-terminal telopeptide fragments of type I collagen (CTX-I) and type II collagen (CTX-II) levels were determined by enzyme-linked immunosorbent assay, and serum levels of bone-specific alkaline phosphatase (BALP) and osteocalcin were determined by an enzyme immunoassay. Levels of biochemical markers were compared with those of 70 age-matched healthy men. RESULTS: Patients with AS had significantly higher mean urinary CTX-I and CTX-II levels than control subjects (p < 0.05). Elevated urinary CTX-I levels correlated well with BASDAI, femoral BMD, and femoral T score (p < 0.05), and elevated urinary CTX-II levels correlated well with spinal BASRI (p < 0.05) in patients with AS. Mean serum BALP and osteocalcin levels did not differ between patients and controls and did not show any significant correlations with BMD, BASDAI, or BASRI in men with AS. Conclusions: Elevated CTX-I reflects disease activity and loss of femoral BMD while elevated CTX-II levels correlate well with radiographic damage of the spine, suggesting the usefulness of these markers for monitoring disease activity, loss of BMD, and radiographic damage in men with AS.


Subject(s)
Adolescent , Adult , Humans , Male , Alkaline Phosphatase/blood , Biomarkers/analysis , Bone Density , Bone and Bones/metabolism , Cartilage/metabolism , Collagen Type I/urine , Collagen Type II/urine , Cross-Sectional Studies , Enzyme-Linked Immunosorbent Assay , Immunoassay/methods , Osteocalcin/blood , Spondylitis, Ankylosing/metabolism
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