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.
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.
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.
ABSTRACT
Purpose@#To investigate correlations between myositis-specific autoantibodies (MSA) or myositis-associated antibodies (MAA) and clinical features, thereby demonstrating the utility of clinicoserologic classification in idiopathic inflammatory myopathies (IIM) patients. @*Materials and Methods@#We conducted a multicenter study of 108 adult patients (age ≥18 years) who were diagnosed with IIM by Peter and Bohan criteria or 2004 European Neuromuscular Centre (ENMC) criteria. Clinical data were obtained by medical record review. Immunoblot assay with Euroline strip (EUROIMMUN, Germany) was performed using the sera of dermatomyositis (DM, n=56), polymyositis (PM, n=45), amyopathic DM (n=5), DM sine dermatitis (n=1), and immune mediated necrotizing myopathy (n=1) patients. Patients were classified based on two classifications: 2017 EULAR/ACR and novel clinicoserologic classification. @*Results@#According to 2017 EULAR/ACR criteria, DM and PM were the most and the second most frequent entities. Overlap myositis was the major entity of IIM, and the frequency of PM was significantly lower when applying clinicoserologic classification criteria. Sixty-nine (63.9%) patients had one or more MSA, and 61 (56.5%) patients had one or more MAA. Interstitial lung disease was closely associated with anti-MDA5 and anti-ARS, and DM-specific skin lesions were frequently observed in patients with antiTIF1γ, anti-SRP, and anti-MDA5. @*Conclusion@#The clinicoserologic criteria based on MSA/MAA positivity could reflect more precise clinical features of IIM. Establishment of a laboratory system routinely available to screen for MSA/MAA status will be beneficial to provide precise diagnosis and proper management of IIM patients.
ABSTRACT
Objective@#The increase in mortality in rheumatoid arthritis (RA) patients with interstitial lung disease (ILD) is well known. However, there are few studies on serum markers that can evaluate acute exacerbation or prognosis in RA-ILD patients. The purpose of this study was to identify the association between biomarkers and lung lesions in patients with RA-ILD. @*Methods@#We analyzed 153 patients with serum samples in a prospective, multicenter cohort of Korean RA-ILD patients. The serum levels of biomarkers, matrix metalloproteinase (MMP-7), surfactant protein-D (SP-D), and Krebs von den Lungen-6 (KL-6) were measured and correlated with forced vital capacity (FVC), diffusing capacity for carbon monoxide (DLCO) and the results of computed tomography (CT). CT results were interpreted semi-quantitatively according to the extent of lung lesions (grade 1, 0%∼ 25%; grade 2, 26%∼50%; grade 3, 51%∼75%; grade 4, 76%∼100%). @*Results@#MMP-7, SP-D, and KL-6 were negatively correlated with FVC (MMP-7, r=−0.267, p=0.001; SP-D, r=−0.250, p=0.002; KL-6, r=−0.223, p=0.006) and DLCO (MMP-7, r=−0.404, p＜0.001; SP-D, r=−0.286, p=0.001; KL-6, r=−0.226, p=0.007). In addition, MMP-7, SP-D, and KL-6 tended to increase with higher grades of lung lesions on CT (MMP-7, p=0.013; SP-D, p＜0.001; KL-6, p＜0.001). @*Conclusion@#MMP-7, SP-D, and KL-6 can be used to evaluate the functional and anatomical status of lung involvement in the RA-ILD patients.
ABSTRACT
Purpose@#To investigate correlations between myositis-specific autoantibodies (MSA) or myositis-associated antibodies (MAA) and clinical features, thereby demonstrating the utility of clinicoserologic classification in idiopathic inflammatory myopathies (IIM) patients. @*Materials and Methods@#We conducted a multicenter study of 108 adult patients (age ≥18 years) who were diagnosed with IIM by Peter and Bohan criteria or 2004 European Neuromuscular Centre (ENMC) criteria. Clinical data were obtained by medical record review. Immunoblot assay with Euroline strip (EUROIMMUN, Germany) was performed using the sera of dermatomyositis (DM, n=56), polymyositis (PM, n=45), amyopathic DM (n=5), DM sine dermatitis (n=1), and immune mediated necrotizing myopathy (n=1) patients. Patients were classified based on two classifications: 2017 EULAR/ACR and novel clinicoserologic classification. @*Results@#According to 2017 EULAR/ACR criteria, DM and PM were the most and the second most frequent entities. Overlap myositis was the major entity of IIM, and the frequency of PM was significantly lower when applying clinicoserologic classification criteria. Sixty-nine (63.9%) patients had one or more MSA, and 61 (56.5%) patients had one or more MAA. Interstitial lung disease was closely associated with anti-MDA5 and anti-ARS, and DM-specific skin lesions were frequently observed in patients with antiTIF1γ, anti-SRP, and anti-MDA5. @*Conclusion@#The clinicoserologic criteria based on MSA/MAA positivity could reflect more precise clinical features of IIM. Establishment of a laboratory system routinely available to screen for MSA/MAA status will be beneficial to provide precise diagnosis and proper management of IIM patients.
ABSTRACT
Objective@#The increase in mortality in rheumatoid arthritis (RA) patients with interstitial lung disease (ILD) is well known. However, there are few studies on serum markers that can evaluate acute exacerbation or prognosis in RA-ILD patients. The purpose of this study was to identify the association between biomarkers and lung lesions in patients with RA-ILD. @*Methods@#We analyzed 153 patients with serum samples in a prospective, multicenter cohort of Korean RA-ILD patients. The serum levels of biomarkers, matrix metalloproteinase (MMP-7), surfactant protein-D (SP-D), and Krebs von den Lungen-6 (KL-6) were measured and correlated with forced vital capacity (FVC), diffusing capacity for carbon monoxide (DLCO) and the results of computed tomography (CT). CT results were interpreted semi-quantitatively according to the extent of lung lesions (grade 1, 0%∼ 25%; grade 2, 26%∼50%; grade 3, 51%∼75%; grade 4, 76%∼100%). @*Results@#MMP-7, SP-D, and KL-6 were negatively correlated with FVC (MMP-7, r=−0.267, p=0.001; SP-D, r=−0.250, p=0.002; KL-6, r=−0.223, p=0.006) and DLCO (MMP-7, r=−0.404, p＜0.001; SP-D, r=−0.286, p=0.001; KL-6, r=−0.226, p=0.007). In addition, MMP-7, SP-D, and KL-6 tended to increase with higher grades of lung lesions on CT (MMP-7, p=0.013; SP-D, p＜0.001; KL-6, p＜0.001). @*Conclusion@#MMP-7, SP-D, and KL-6 can be used to evaluate the functional and anatomical status of lung involvement in the RA-ILD patients.
ABSTRACT
Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease with highly variable clinical and immunological manifestations. Classification and diagnosis of SLE are complicated by the multi-organ nature of the disease and by our incomplete understanding of its pathophysiology. The 1997 update of the 1982 American College of Rheumatology (ACR) criteria for SLE has been widely used for classification of SLE. In order to improve clinical relevance and early diagnosis, the Systemic Lupus Erythematosus International Collaborating Clinics (SLICC) group suggested the 2012 SLICC criteria. These sets of classification criteria have unweighted lists of various serological and clinical findings typical of SLE, can be fulfilled by reaching a sum score of points. The only exception is biopsy-proven lupus nephritis with autoantibodies in the 2012 SLICC criteria. In an attempt to overcome limitations of the previous sets of SLE classification criteria, the new 2019 SLE European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) classification criteria for SLE have been recently published. The 2019 EULAR/ACR criteria include positive ANA at least once as obligatory entry criterion; followed by additive hierarchically clustered and weighted criteria. The structure and weighting of criteria constitute a paradigm shift in the classification of SLE. In the validation cohort, the new criteria had a sensitivity of 96.1% and specificity of 93.4%. This review attempts to delineate the history, performance and limitations of the current sets of SLE criteria.
ABSTRACT
Background@#We purposed to evaluate the seasonality and associated factors of the incidence of gout attacks in Korea. @*Methods@#We prospectively enrolled patients with gout attacks who were treated at nine rheumatology clinics between January 2015 and July 2018 and followed them for 1-year. Demographic data, clinical and laboratory features, and meteorological data including seasonality were collected. @*Results@#Two hundred-five patients (men, 94.1%) were enrolled. The proportion of patients with initial gout attacks was 46.8% (n = 96). The median age, body mass index, attack duration, and serum uric acid level at enrollment were 50.0 years, 25.4, 5.0 days, and 7.4 mg/dL, respectively. Gout attacks were most common during spring (43.4%, P < 0.001) and in March (23.4%, P < 0.001). A similar pattern of seasonality was observed in the group with initial gout attacks. Alcohol was the most common provoking factor (39.0%), particularly during summer (50.0%). The median diurnal temperature change on the day of the attack was highest in the spring (9.8°C), followed by winter (9.3°C), fall (8.6°C), and summer (7.1°C) (P = 0.027). The median change in humidity between the 2 consecutive days (the day before and the day of the attack) was significantly different among the seasons (3.0%, spring; 0.3%, summer; −0.9%, fall; −1.2%, winter; P = 0.015). One hundred twenty-five (61%) patients completed 1-year follow-up (51% in the initial attack group). During the follow-up period, 64 gout flares developed (21 in the initial attack group). No significant seasonal variation in the follow-up flares was found. @*Conclusion@#In this prospective study, the most common season and month of gout attacks in Korea are spring and March, respectively. Alcohol is the most common provoking factor, particularly during summer. Diurnal temperature changes on the day of the attack and humidity changes from the day before the attack to the day of the attack are associated with gout attack in our cohort.
ABSTRACT
Background@#To elucidate the achievement rates of imaging remission and to examine the characteristics associated with imaging remission status among patients with rheumatoid arthritis (RA) who have attained clinical remission. @*Methods@#Ninety-seven patients with RA patients who had attained clinical remission, defined by DAS28-ESR < 2.6 were enrolled. Power Doppler ultrasonography (PDUS) was performed on 16 joints and 2 tendons, including the first to third metacarpophalangeal, second and third proximal interphalangeal, radiocarpal (RC), second and third metatarsophalangeal joints, and extensor carpi ulnaris tendons. They were graded based on a dichotomous assessment. The clinical and laboratory data of patients who had attained imaging remission were compared to those of patients who had attained only clinical remission. @*Results@#The imaging remission rate was 51.5% in patients who had attained clinical remission. Forty-seven patients (48.5%) were PDUS positive. Power Doppler was detected most frequently in the right RC joint (n = 40). PDUS positive patients had higher evaluator global assessment (EGA) scores (P < 0.001) than PDUS negative patients. PDUS positive patients also had higher clinical disease activity index and simplified clinical disease activity index scores than PDUS negative patients. Patients who had attained imaging remission had lower pain scores and used nonsteroidal anti-inflammatory drugs less frequently. Patients who had attained imaging remission had higher rheumatoid factor (RF) and anti-cyclic citrullinated peptide levels. A low EGA score was found to be a predictor of imaging remission achievement among patients who had attained clinical remission. @*Conclusion@#Only 51.5% of the patients with RA who had attained clinical remission were also in imaging remission. Patients who had attained imaging remission had lower EGA scores and higher RF levels than patients who had attained only clinical remission.
ABSTRACT
OBJECTIVE: Productivity loss was compared by 3-stage of disease activity and associations between higher disease activity and high productivity loss were identified. METHODS: Data were extracted from Rheumatoid Arthritis (RA) Patient-reported Outcomes Research, which enrolled 2,000 RA patients (>20-year) on disease-modifying-antirheumatic-drugs (DMARDs) (≥6-month) from December 2012 to June 2013. This included 1,457 RA patients with the disease activity score (DAS-28-ESR) in their medical charts. Productivity loss in time and indirect cost was estimated using The World Health Organization Health and Work Performance Questionnaire (HPQ). Baseline characteristics and productivity loss outcomes were compared according to DAS-28-ESR groups. RESULTS: 84.4% were females, 54.2% had low DAS-28-ESR ( 5.1). Patients with moderate to high DAS-28-ESR had higher lost productivity time (LPT) and monthly costs of LPT than those with low DAS-28-ESR (time in hours: 110.0±58.4 vs. 132.4±57.2 vs. 71.5±52.0, p < 0.0001; monthly costs of LPT in 1,000 Korean won: 1,097±607 vs. 1,302±554 vs. 741±531, p < 0.0001). Multiple regression analyses revealed significant associations with high LPT in high (adjusted odds ratio [OR]=3.87, 95% confidence interval [CI]: 2.18∼6.87) and moderate DAS-28-ESR (adjusted OR=1.88, 95% CI: 1.41∼2.52) compared to low DAS-28-ESR. In addition, positive associations with high monthly costs of LPT were observed in high (adjusted OR=3.45, 95% CI: 1.98∼5.99) and moderate DAS-28-ESR (adjusted OR=1.93, 95% CI: 1.43∼2.54) compared to low DAS-28-ESR. CONCLUSION: Timely therapeutic strategies should be taken into consideration given that the RA patients with moderate to high DAS-28-ESR showed strong associations with high productivity loss for effective management of RA.
Subject(s)
Female , Humans , Arthritis, Rheumatoid , Efficiency , Odds Ratio , Outcome Assessment, Health Care , Work Performance , World Health OrganizationABSTRACT
In the above article, the financial grant has been erroneously omitted.
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 , RituximabABSTRACT
Urticarial vasculitis is a rare disorder that principally manifests with recurrent urticarial, sometimes hemorrhagic, skin lesions and/or angioedema. Its clinical presentation is not always limited to cutaneous lesions and it can potentially affect other organs, such as the joints, lungs, kidneys, and eyes. Systemic involvement can either be present at the onset of disease or develop over time. In cases with systemic manifestations, urticarial vasculitis is more likely to be associated with a low complement level. We present the case of a teenage boy with hypocomplementemic urticarial vasculitis syndrome (HUVS) that occurred shortly following swine-origin influenza A virus infection in 2009. Afterwards, HUVS was systemically complicated with myositis and membranous nephropathy that developed several months and about 2 years after its onset, respectively. A combination of glucocorticoid and immunosuppressive agents has been used to effectively control disease activity.
Subject(s)
Humans , Male , Angioedema , Complement System Proteins , Glomerulonephritis, Membranous , Immunosuppressive Agents , Influenza A virus , Joints , Kidney , Lung , Myositis , Skin , VasculitisABSTRACT
OBJECTIVE: The aim of this study was to determine recurrence factors and reproductive outcomes of laparoscopic myomectomy (LM) and minilaparotomic myomectomy (MM) for treating uterine leiomyomas. METHODS: Between 2007 and 2013, 160 patients underwent myomectomy, including 122 who underwent LM and 38 who underwent MM. Patients were followed up for recurrence based on pelvic ultrasound exams. Only patients who were followed up for a minimum of two years were selected for this retrospective study. Pregnancy rate, delivery, and delivery methods were compared between the two groups to evaluate reproductive outcomes. Furthermore, mean age, body mass index, preoperative administration of gonadotropin-releasing hormone agonist (GnRHa), and characteristics of leiomyomas were investigated to determine recurrence factors. RESULTS: The mean body mass index in the MM group was significantly (P=0.048) higher than that in the LM group. The number and the largest diameter of removed leiomyoma were also significantly higher in the MM group (both P=0.001). Logistic regression after adjusting significantly different characteristics showed that the LM group had shorter (P=0.020) postoperative hospitalization days compared to the MM group. Other outcome variables including recurrence rate were not significantly different between the two groups. Reproductive outcomes such as pregnancy rate, delivery, and delivery methods were not significantly different between the two groups. Preoperative GnRHa therapy was the only significant (P=0.039) recurrence factor after myomectomy. CONCLUSION: This study showed that LM and MM had similar recurrence rates and reproductive outcomes. The only recurrence factor of significance was preoperative administration of GnRHa.
Subject(s)
Humans , Body Mass Index , Gonadotropin-Releasing Hormone , Hospitalization , Laparoscopy , Laparotomy , Leiomyoma , Logistic Models , Pregnancy Rate , Recurrence , Retrospective Studies , Ultrasonography , Uterine MyomectomyABSTRACT
Remission is a primary end point of in clinical practice and trials of treatments for rheumatoid arthritis (RA). The 2011 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) remission criteria were developed to provide a consensus definition of remission. This study aimed to assess the concordance between the new remission criteria and the physician’s clinical judgment of remission and also to identify factors that affect the discordance between these two approaches. A total of 3,209 patients with RA were included from the KORean Observational Study Network for Arthritis (KORONA) database. The frequency of remission was evaluated based on each approach. The agreement between the results was estimated by Cohen's kappa (κ). Patients with remission according to the 2011 ACR/EULAR criteria (i.e. the Boolean criteria) and/or physician judgment (n = 855) were divided into three groups: concordant remission, the Boolean criteria only, and physician judgment only. Multinomial logistic regression analysis was used to identify factors responsible for the assignment of patients with remission to one of the discordant groups rather than the concordant group. The remission rates using the Boolean criteria and physician judgment were 10.5% and 19.9%, respectively. The agreement between two approaches for remission was low (κ = 0.226) and the concordant remission rate was only 5.5% (n = 177). Pain affected classification in both discordant groups, whereas fatigue was associated with remission only by physician clinical judgment. The Boolean criteria were more stringent than clinical judgment. Patient subjective symptoms such as pain and fatigue were associated with discordance between the two approaches.
Subject(s)
Humans , Arthritis , Arthritis, Rheumatoid , Classification , Consensus , Fatigue , Judgment , Logistic Models , Observational Study , Rheumatic DiseasesABSTRACT
SAPHO syndrome is a rare inflammatory, pseudoinfectious disease. Initially it was an acronym for Syndrome Acne Pustulosis Hyperostosis Osteitis, and the meaning of S was later changed to synovitis. It occurs predominantly in children and adults and is not common over 60 years. The most common clinical presentation is osteoarticular involvement at the anterior chest wall and skin manifestations may be evident, but it could occur years earlier or develop later. We report on two cases of mother and daughter. A 51-year-old female was diagnosed with SAPHO syndrome with costochondritis and palmoplantar pustulosis. Five years later, her 31-year-old daughter presented with similar skin manifestations of the hand and foot.
Subject(s)
Adult , Child , Female , Humans , Middle Aged , Acne Vulgaris , Acquired Hyperostosis Syndrome , Foot , Hand , Hyperostosis , Mothers , Nuclear Family , Osteitis , Psoriasis , Skin Manifestations , Synovitis , Thoracic WallABSTRACT
This study was performed to evaluate the contribution of adiponectin to the production of interleukin (IL)-6, IL-8, vascular endothelial growth factor (VEGF), matrix metalloproteinase (MMP)-1 and MMP-13 in human endothelial cells and osteoblasts in arthritic joints. Cultured human umbilical vascular endothelial cells (HUVECs) and osteoblasts were stimulated with adiponectin (1 or 10 mug ml-1) or IL-1beta (0.1 ng ml-1) in the presence or absence of hypoxia for 24 h. The protein expression patterns were examined by analyzing culture supernatants using the enzyme-linked immunosorbent assay (ELISA). Adiponectin significantly stimulated the production of VEGF, MMP-1 and MMP-13 in osteoblasts but not in endothelial cells, whereas it significantly stimulated the production of IL-6 and IL-8 in both endothelial cells and osteoblasts. The increase in VEGF production induced by adiponectin was significantly greater than that induced by IL-1beta. The production of IL-6 and IL-8 in adiponectin-stimulated endothelial cells was approximately 10-fold higher than that in IL-1beta-stimulated endothelial cells; in osteoblasts, adiponectin-induced IL-6 and IL-8 secretion was approximately twofold higher than that induced by IL-1beta. In addition, IL-8 production in endothelial cells was approximately sevenfold higher than in osteoblasts. However, IL-6 levels were similar between the two cell types, suggesting that adiponectin may be involved in the production of IL-8 in endothelial cells, which may have an important role in neutrophil recruitment to arthritic joints. Furthermore, the increases in protein expression induced by adiponectin were differentially regulated by hypoxia. In conclusion, adiponectin has a more important role than does IL-1beta in the production of mediators that drive synovitis and joint destruction in endothelial cells and osteoblasts at physiological concentrations.
Subject(s)
Humans , Adiponectin/pharmacology , Arthritis, Rheumatoid/metabolism , Cell Hypoxia , Cell Line , Human Umbilical Vein Endothelial Cells/drug effects , Interleukin-6/genetics , Interleukin-8/genetics , Matrix Metalloproteinase 1/genetics , Osteoblasts/drug effects , Vascular Endothelial Growth Factor A/geneticsABSTRACT
OBJECTIVE: The purpose of this study is to examine the difference between the numbers of patients in rheumatoid arthritis (RA) who are eligible to TNF inhibitors by the past Korean National Health Insurance reimbursement guideline and by the disease activity score with 28-joint assessment (DAS28) based criteria. METHODS: Data were obtained from a multi-center registry for biologics users in Korean RA patients, BIOlogics Pharmacoepidemiologic StudY (BIOPSY). DAS28 was calculated based on either ESR or CRP, and DAS28 of more than 5.1 or between 3.2 and 5.1 with radiographic changes was defined as a cut-off point for the initiation of TNF inhibitors. For the maintenance criteria, we used both of improving in DAS28 score (>1.2) and low disease activity (DAS 28<3.2). Differences between the numbers in each step by two criteria were described with Chi-square test and Kappa agreement. RESULTS: Of the 489 patients in BIOPSY, 299 were included in this study. Among them, 278 patients (93.0%) were eligible of TNF inhibitors when we applied the new initiation criteria with DAS28-ESR, and 244 patients (81.6%) were indicated for TNF inhibitors with DAS28-CRP. For the maintenance criteria, a low disease activity (DAS28<3.2) in 3 months after starting TNF inhibitors is too strict for achieving (33.6% with DAS28-ESR and 50.0% with DAS28-CRP). Instead, decreasing DAS28 by more than 1.2 is more reasonable as a tool for deciding early responsiveness of TNF inhibitors in RA patients (81.2% both with DAS28-ESR and DAS28-CRP). CONCLUSION: Our results show that the candidates for TNF inhibitors will be enormously changed according to a change in the reimbursement criteria. To define appropriate patients to receive TNF inhibitors, a further study with regard to the impact of changes in the reimbursement criteria on the outcomes of RA patients will be required.