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1.
Artigo em Inglês | MEDLINE | ID: mdl-38479822

RESUMO

OBJECTIVES: To develop a model for predicting flares after tapering the dose of tumour necrosis factor inhibitors (TNFi) in patients with axial spondyloarthritis (axSpA). METHODS: Data were obtained from the Korean College of Rheumatology Biologics and Targeted Therapy Registry. In total, 526 patients who received the standard-dose TNFi for at least 1 year and tapered their dose were included in the derivation cohort. The main outcome was a flare occurrence defined as an Ankylosing Spondylitis Disease Activity Score with C-reactive protein (ASDAS-CRP) score of ≥ 2.1 after 1 year of TNFi tapering. The final prediction model was validated using an independent cohort. RESULTS: Among 526 patients, 127 (24.1%) experienced flares. The final prediction model included negative human leucocyte antigen B27 (ß = 1.088), inflammatory back pain (ß = 1.072), psoriasis (ß = 1.567), family history of SpA (ß = 0.623), diabetes mellitus (ß = 1.092), TNFi tapering by ≥ 50% of the standard-dose (ß = 0.435), ASDAS-CRP at tapering (ß = 1.029), and Bath Ankylosing Spondylitis Functional Index score at tapering (ß = 0.194) as covariates. It showed an excellent discrimination performance (AUC = 0.828). According to the predictive risk, patients were classified into three groups (low-, intermediate-, and high-risk). The probabilities of flares in these groups were 4.5%, 18.1%, and 61.8%, respectively. The performance of the model in the validation cohort was also comparable. CONCLUSION: The established prediction model accurately predicted the risk of flares after TNFi dose tapering in patients with axSpA using eight simple clinical parameters, which could be helpful to select appropriate patients for tapering their TNFi without flare in daily clinical practice.

2.
Clin Exp Rheumatol ; 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38634363

RESUMO

OBJECTIVES: This study aimed to identify the risk factors associated with overall adverse events (AEs) and infections in patients with rheumatoid arthritis (RA) and comorbid interstitial lung disease (ILD), receiving biologic or targeted synthetic disease-modifying anti-rheumatic drugs (b/tsDMARDs), using data from the Korean College of Rheumatology Biologics registry. METHODS: We analysed data from a cohort of 2,266 adult patients with RA who received b/tsDMARDs, including 169 patients with comorbid ILD. We identified the risk factors for overall AEs and infections in both the all RA group and the subgroup of patients with RA-ILD and investigated the impact of infections on mortality in patients with RA-ILD. RESULTS: Among all patients with RA, 45.7% withdrew b/tsDMARDs, whereas among those with RA-ILD, a higher proportion of 57.4% withdrew their treatment regimen. The main reason for withdrawing b/tsDMARDs in the RA-ILD group was AEs, with infections accounting for the largest proportion of reported AEs. In multivariable analysis of the risk factors for overall AEs and infections in the RA-ILD group, older age was identified as a risk factor for overall AEs (odds ratio [OR], 3.01; p=0.014), and only a current smoking status was identified as a risk factor for infections (OR, 2.11; p=0.035). CONCLUSIONS: Patients with RA-ILD exhibited a higher rate of b/tsDMARDs withdrawal due to overall AEs and infections than those with RA without ILD. In the RA-ILD group, older age was identified as a risk factor for overall AEs, whereas a current smoking status was identified as a risk factor for infections.

3.
J Korean Med Sci ; 39(4): e37, 2024 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-38288538

RESUMO

This retrospective cohort study aimed to compare coronavirus disease 2019 (COVID-19)-related clinical outcomes between patients with and without gout. Electronic health record-based data from two centers (Seoul National University Hospital [SNUH] and Boramae Medical Center [BMC]), from January 2021 to April 2022, were mapped to a common data model. Patients with and without gout were matched using a large-scale propensity-score algorithm based on population-level estimation methods. At the SNUH, the risk for COVID-19 diagnosis was not significantly different between patients with and without gout (hazard ratio [HR], 1.07; 95% confidence interval [CI], 0.59-1.84). Within 30 days after COVID-19 diagnosis, no significant difference was observed in terms of hospitalization (HR, 0.57; 95% CI, 0.03-3.90), severe outcomes (HR, 2.90; 95% CI, 0.54-13.71), or mortality (HR, 1.35; 95% CI, 0.06-16.24). Similar results were obtained from the BMC database, suggesting that gout does not increase the risk for COVID-19 diagnosis or severe outcomes.


Assuntos
COVID-19 , Gota , Humanos , Estudos Retrospectivos , SARS-CoV-2 , Teste para COVID-19 , Gota/complicações , Gota/diagnóstico , República da Coreia/epidemiologia
4.
Rheumatol Int ; 43(8): 1507-1513, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-36809556

RESUMO

The diagnostic performance of band intensity (BI) cut-offs, adjusted by a positive control band (PCB) in a line-blot assay (LBA) for myositis-related autoantibodies (MRAs) is investigated. Sera from 153 idiopathic inflammatory myositis (IIM) patients with available immunoprecipitation assay (IPA) data and 79 healthy controls were tested using the EUROLINE panel. Strips were evaluated for BI using the EUROLineScan software, and the coefficient of variation (CV) was calculated. Sensitivity and specificity, area under the curve (AUC), and the Youden's index (YI) were estimated at non-adjusted or PCB-adjusted cut-off values. Kappa statistics were calculated for IPA and LBA. Although inter-assay CV for PCB BI was 3.9%, CV was 12.9% in all samples, and a significant correlation was found between BIs of PCB and seven MRAs (all P < 0.05). At adjusted BI (aBI) > 10, the negative conversion rate of myositis-specific autoantibody (MSA)-positivity at BI > 10 was 11.5% in controls and 1.3% in patients. The specificity, AUC, and YI for MSAs at aBI > 10 or > 20 were higher than those at non-adjusted cut-off values. Additionally, AUC (0.720), YI (0.440), and the prevalence of MRAs with kappa > 0.60 (58.3%) were the highest at aBI > 20. The overall sensitivity and specificity for MSAs were 50.3% and 93.7% at aBI > 20, respectively, and 59.5% and 65.8% with BI > 10, respectively. The diagnostic performance of LBA can be improved using PCB-adjusted BIs. aBI > 20 is the optimal cut-off for IIM diagnosis using the EUROLINE LBA panel.


Assuntos
Miosite , Humanos , Autoanticorpos , Sensibilidade e Especificidade
5.
J Korean Med Sci ; 38(35): e266, 2023 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-37667577

RESUMO

BACKGROUND: The Gout Impact Scale (GIS), part of the Gout Assessment Questionnaire 2.0, measures gout-specific health-related quality of life (HRQOL). This study aimed to translate the GIS into Korean and validate the Korean version (K-GIS) using generic HRQOL measures. METHODS: The GIS was translated into Korean and back-translated into English. We asked patients aged 18 years or older who met the 2015 gout classification criteria to fill out the questionnaires (from January 2022 to June 2022); the K-GIS (5 scales [0-100 scores each]), along with the Korean version of Health Assessment Questionnaire (HAQ) and EuroQol-5 dimension (EQ-5D). We investigated the internal consistency, construct validity, and discriminative validity for gout characteristics of K-GIS. The K-GIS form was administrated to patients 4 weeks later to assess the test-retest reliability using the intraclass correlation coefficient (ICC). RESULTS: One hundred patients completed the questionnaire. The mean ± standard deviation age of the patients was 53.0 ± 15.1 years, and 99.0% of the patients were men. All scales had high degree of internal consistency (Cronbach's α = 0.59 to 0.96) and test-retest reliability (n = 18, ICC = 0.83 to 0.94, all P < 0.001), except for unmet gout treatment needs. Weak-to-moderate correlations were observed between the K-GIS scales and HAQ or EQ-5D (r = 0.21 to 0.46). The K-GIS scores were significantly higher in the presence of bone erosion, absence of urate-lowering therapy, serum urate levels > 6 mg/dL, frequent gout flares in the past year, and fewer comorbidities. In contrast, neither the HAQ nor the EQ-5D could discern these subsets of patients. CONCLUSION: The K-GIS is a reliable and valid HRQOL measure for patients with gout. Higher K-GIS scores were associated with clinical characteristics leading to unfavorable outcomes, which were not demonstrated by the HAQ and EQ-5D.


Assuntos
Gota , Qualidade de Vida , Masculino , Humanos , Feminino , Reprodutibilidade dos Testes , Ácido Úrico , Gota/diagnóstico , República da Coreia
6.
J Korean Med Sci ; 37(33): e253, 2022 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-35996930

RESUMO

BACKGROUND: Clinical characteristics and manifestations of psoriatic arthritis (PsA) have been extensively studied in western countries, yet data of Korean patients with PsA are very limited. We aimed to investigate the clinical traits of patients with PsA and dissect the characteristics of those with axial involvement. METHODS: In this observational study, we analyzed clinical data of 109 patients with PsA who were enrolled in the Korean College of Rheumatology Biologics and Targeted Therapy registry between December 2012 and March 2022 at the time point of initiating or switching to a biologic agent. Data from 2,221 patients with ankylosing spondylitis (AS) registered during the same period were also analyzed. We divided patients with PsA into patients with or without axial involvement and then added AS patients with psoriasis (total three subgroups) for comparative analyses. RESULTS: Asymmetric oligoarthritis was the most common clinical manifestation in patients with PsA, followed by symmetric polyarthritis and spondylitis. Our analysis indicated that methotrexate and sulfasalazine were the two most prescribed disease-modifying antirheumatic drugs for patients with PsA before starting biologic therapy. The patients with psoriatic spondylitis had more peripheral joint involvement (P = 0.016), less prior uveitis (P < 0.001), and lower human leukocyte antigen B27 (HLA-B27) positivity (P < 0.001) than the AS patients with psoriasis. Furthermore, syndesmophytes and radiographic sacroiliitis were prevalent among patients with PsA and AS patients with psoriasis who had the HLA-B27 gene. CONCLUSION: Our study shows that the degree of peripheral arthritis is less severe in Korean patients with PsA who require biologics and reestablishes that psoriatic spondylitis is a common and important clinical pattern in Korean patients with PsA. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01965132.


Assuntos
Artrite Psoriásica , Produtos Biológicos , Psoríase , Espondilite Anquilosante , Espondilite , Artrite Psoriásica/diagnóstico , Artrite Psoriásica/tratamento farmacológico , Produtos Biológicos/uso terapêutico , Terapia Biológica , Antígeno HLA-B27/uso terapêutico , Humanos , Psoríase/diagnóstico , Psoríase/tratamento farmacológico , Espondilite/tratamento farmacológico , Espondilite Anquilosante/diagnóstico , Espondilite Anquilosante/tratamento farmacológico
7.
Clin Exp Rheumatol ; 39(2): 269-278, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32324126

RESUMO

OBJECTIVES: We aimed to evaluate the clinical outcomes and safety of biologic and targeted synthetic disease-modifying anti-rheumatic drugs (b/tsDMARDs) and to identify predictors of treatment responses to b/tsDMARDs in elderly patients with rheumatoid arthritis (RA). METHODS: Data from the nationwide cohort of elderly (≥ 65 years) patients enrolled in the KOBIO Registry were analysed. Clinical outcomes were assessed, including changes in the Simplified Disease Activity Index, after treatment. Adverse events and reasons for drug discontinuation were assessed. Multivariable logistic regression analyses were performed to determine which baseline variables affected treatment responses and adverse events (AE). RESULTS: Elderly patients treated with b/tsDMARDs (n=355) or conventional synthetic DMARDs (csDMARDs) (n=104) were included. The median age was 70 years and 77% were female. After 1 year, 63% of patients in the b/tsDMARD group and 68% in the csDMARD group achieved remission or low disease activity (LDA). Overall, 27% of patients in the b/tsDMARDs group and 24% in the csDMARDs group experienced AE. A total of 43.4% of patients on b/tsDMARDs discontinued therapy due to lack of effectiveness (27%), AE (34%), or other reasons (35%). The estimated median retention of b/tsDMARDs was 2.5 years. Male sex and non-exposure to tobacco at baseline were independent factors associated with achieving remission or LDA after 1 year. Interstitial lung disease (ILD) was the most prominent comorbidity associated with AE. CONCLUSIONS: Treatment with b/tsDMARDs is effective and well tolerated in elderly patients with RA; nonetheless, ILD is a key comorbidity that should be monitored carefully.


Assuntos
Antirreumáticos , Artrite Reumatoide , Produtos Biológicos , Idoso , Antirreumáticos/efeitos adversos , Artrite Reumatoide/diagnóstico , Artrite Reumatoide/tratamento farmacológico , Produtos Biológicos/efeitos adversos , Feminino , Humanos , Masculino , Pacientes , Sistema de Registros
8.
BMC Musculoskelet Disord ; 22(1): 244, 2021 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-33663463

RESUMO

BACKGROUND: Placebo can have a significant therapeutic effect in patients with hand osteoarthritis (OA). This aim of the study is to identify factors associated with a clinically meaningful placebo response in patients with hand OA. METHODS: This post-hoc analysis of two double-blind, placebo-controlled, randomized trials (RCTs) investigating the efficacy of GCSB-5 or diacerein as treatments for hand OA analyzed the efficacy of a placebo. Clinical and laboratory factors associated with a clinically meaningful response, defined as an improvement in the Australian/Canadian Osteoarthritis Hand Index (AUSCAN) pain score > 10 at 4 weeks relative to baseline, were identified. RESULTS: The mean improvement in the AUSCAN pain score was - 6.0 ± 20.3, with marked variation between 143 hand OA patients (range: - 76.4 to 33.2). A clinically meaningful improvement was observed in 54 (37.8%) patients. Placebo responders had worse AUSCAN pain scores (55.7 ± 19.7 vs. 43.6 ± 21.6, p = 0.001) and a worse AUSCAN stiffness (68.2 ± 20.5 vs. 57.5 ± 24.5, p = 0.008) at baseline than non-responders. Improvements in pain correlated with the baseline pain level (Pearson r = - 427, p < 0.001). Structural joint changes such as tender, swollen, enlarged, or deformed joint counts did not differ between placebo responders and non-responders. In a multivariable analysis, only baseline AUSCAN pain was associated with a clinically meaningful placebo response (OR: 1.054, 95% CI [1.019-1.089], p = 0.002). CONCLUSIONS: High levels of pain at baseline are predictive of a clinically meaningful placebo response in patients with hand OA. Further studies are needed to optimize and utilize the benefit of placebo responses in patients with hand OA.


Assuntos
Osteoartrite , Austrália , Canadá , Método Duplo-Cego , Humanos , Osteoartrite/diagnóstico , Osteoartrite/tratamento farmacológico , Medição da Dor , Efeito Placebo , Ensaios Clínicos Controlados Aleatórios como Assunto
10.
J Korean Med Sci ; 36(12): e95, 2021 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-33783147

RESUMO

The coronavirus disease 2019 (COVID-19) pandemic has caused more than 100 million infections and 2 million deaths worldwide. In up to 20% of cases, COVID-19 infection can take a severe, life-threatening course. Therefore, preventive measures such as mask-wearing, hand hygiene, and social distancing are important. COVID-19 vaccines that use novel vaccine technology can prevent up to 95% of infections. However, the uncertainty regarding the efficacy and safety of vaccination in patients with autoimmune inflammatory rheumatic disease (AIIRD), who are immunocompromised due to underlying immune dysfunction and concomitant immunosuppressive treatment, warrants clear guidance. A task force of the Korean College of Rheumatology formulated a set of vaccination guidance based on the currently available data and expert consensus. The currently available COVID-19 vaccines are considered to be safe and effective. Every patient with AIIRD should receive one of the available COVID-19 vaccines unless contraindicated for medical reasons such as prior allergy/anaphylaxis to the COVID-19 vaccine or its components. Patients should continue immunosuppressive treatment for their underlying AIIRD, including biological and targeted synthetic disease-modifying anti-rheumatic drugs (b/tsDMARDs). Corticosteroids should be reduced to the lowest dose possible without aggravating the AIIRD. To improve the vaccine response, methotrexate can be withheld for 1-2 weeks after each vaccination, and the timing of rituximab and abatacept infusion should be adjusted if clinically acceptable. Rheumatologists should play a leading role in educating and vaccinating patients with AIIRD.


Assuntos
Doenças Autoimunes/tratamento farmacológico , Vacinas contra COVID-19/imunologia , COVID-19/prevenção & controle , Guias de Prática Clínica como Assunto , Doenças Reumáticas/tratamento farmacológico , SARS-CoV-2/imunologia , Vacinação , Antirreumáticos/uso terapêutico , Doenças Autoimunes/imunologia , Humanos , Imunossupressores/uso terapêutico , Doenças Reumáticas/imunologia
11.
Clin Exp Rheumatol ; 38(2): 267-274, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31365335

RESUMO

OBJECTIVES: To evaluate the long-term drug retention, efficacy, and safety of the infliximab biosimilar CT-P13 in Korean patients with ankylosing spondylitis (AS) in clinical practice. The primary outcome was drug retention (i.e. time to treatment discontinuation or changing to another biologic) in Korean patients with AS. Additional outcomes included efficacy and safety. METHODS: Data were collected through the Korean College of Rheumatology Biologics (KOBIO) registry (ClinicalTrials.gov identifier: NCT01965132). CT-P13 efficacy was assessed using standard disease activity parameters, and safety was evaluated by adverse events (AEs). RESULTS: Between December 2012 and December 2017, 244 patients with AS treated with CT-P13 were enrolled. Of those, 203 (83.2%) received CT-P13 as first-line therapy. The median duration of treatment was 2.05 years. After 4 years' follow-up, the retention rate of CT-P13 in the overall patient population was 66%. Treatment changes or discontinuations occurred in 38 (15.6%) and 32 (13.1%) patients, respectively. Lack of efficacy was the most common reason for treatment changes, whereas AEs were the most common single cause of discontinuation. Disease activity decreased markedly from baseline following initiation of CT-P13 treatment, and thereafter remained stable. A total of 313 AEs occurred in 118 patients (48.4%); the majority (94.6%) were mild or moderate in severity. The most common treatment-related AEs were infusion or injection-site reactions (4.1% of patients), uveitis (3.7%), and skin rash (3.7%). CONCLUSIONS: In this real-world study, CT-P13 demonstrated encouraging drug retention rates and times, together with reasonable long-term efficacy and safety, in Korean patients with AS.


Assuntos
Antirreumáticos , Medicamentos Biossimilares , Infliximab , Espondilite Anquilosante , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais/uso terapêutico , Antirreumáticos/efeitos adversos , Antirreumáticos/uso terapêutico , Medicamentos Biossimilares/efeitos adversos , Medicamentos Biossimilares/uso terapêutico , Humanos , Infliximab/efeitos adversos , Infliximab/uso terapêutico , Sistema de Registros , República da Coreia , Reumatologia , Índice de Gravidade de Doença , Espondilite Anquilosante/tratamento farmacológico , Espondilite Anquilosante/imunologia , Resultado do Tratamento
12.
Rheumatol Int ; 40(5): 791-798, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31598752

RESUMO

The benefits afforded by tocilizumab (TCZ) in patients with adult-onset Still's disease (AOSD) and systemic juvenile idiopathic arthritis (SJIA) have been described in previous studies. However, few reports have evaluated severe hypersensitivity reactions (HSRs) to TCZ in patients with AOSD or SJIA. We describe three instances of TCZ-induced anaphylactic reactions in AOSD/SJIA patients, and review relevant prior reports on patients with various rheumatic diseases. Two of our cases exhibited shock and cardiovascular collapse; TCZ was discontinued in all three cases. All events occurred within 20 min of TCZ infusion, after at least three prior infusions, indicating an IgE-mediated mechanism and previous sensitization to TCZ. In all three cases, mild HSRs had been observed about 1 month before the anaphylactic events, but pre-medication with antihistamines and corticosteroids failed to prevent anaphylaxis. All three cases had active AOSD or SJIA disease, and were refractory to other immunosuppressive agents. It is essential to be aware that severe anaphylaxis to TCZ can develop in patients with active refractory AOSD or SJIA, and to be cautious when medicating certain patients. Anaphylaxis is a serious condition that can be fatal; TCZ infusion should not be re-challenged via pre-medication in patients who exhibited mild HSRs before TCZ without desensitization.


Assuntos
Anafilaxia/diagnóstico , Anticorpos Monoclonais Humanizados/efeitos adversos , Artrite Juvenil/tratamento farmacológico , Doença de Still de Início Tardio/tratamento farmacológico , Adolescente , Adulto , Idoso , Anticorpos Monoclonais Humanizados/administração & dosagem , Antirreumáticos/administração & dosagem , Antirreumáticos/efeitos adversos , Feminino , Humanos , Infusões Intravenosas/efeitos adversos
13.
J Korean Med Sci ; 34(22): e155, 2019 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-31172694

RESUMO

BACKGROUND: We aimed to assess the performance of the 2015 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) classification criteria for gout in Korean patients with acute arthritis and to compare the performance of the ACR/EULAR criteria to that of other sets of criteria for gout classification. METHODS: Patients with acute arthritis who underwent diagnostic arthrocentesis at one of the four participating rheumatology clinics were consecutively enrolled between February and December 2017. Crystal-proven gout was diagnosed upon confirming the presence of monosodium urate (MSU) crystals in patients with a clinical impression of gout as judged by the rheumatologist. The performance of the ACR/EULAR and other gout classification criteria, including the Rome, New York, American Rheumatism Association (ARA), Mexico, and Netherlands criteria, was analyzed regardless of the presence/absence of MSU crystals. RESULTS: The study enrolled 118 gout patients (all crystal-proven) and 95 non-gout patients. According to the area under the curve, the diagnostic performance was the highest for the ACR/EULAR classification criteria (sensitivity, 80.5%; specificity, 95.8%; area under the curve, 0.966), followed by the Netherlands, Rome, ARA, New York, and Mexico criteria. All six sets of criteria demonstrated lower sensitivity in patients exhibiting the first episode of acute arthritis. CONCLUSION: In Korean patients with acute arthritis, the ACR/EULAR classification criteria outperformed other sets of gout classification criteria even in the absence of information regarding the presence of MSU crystals. However, to enhance diagnostic sensitivity, synovial fluid analysis should be considered in patients with the first episode of acute arthritis.


Assuntos
Artrite/diagnóstico , Gota/diagnóstico , Doença Aguda , Adulto , Idoso , Área Sob a Curva , Artrite/complicações , Estudos de Casos e Controles , Feminino , Gota/classificação , Humanos , Masculino , Microscopia , Pessoa de Meia-Idade , Curva ROC , República da Coreia , Líquido Sinovial/química , Líquido Sinovial/citologia
14.
J Biol Chem ; 292(13): 5392-5404, 2017 03 31.
Artigo em Inglês | MEDLINE | ID: mdl-28193842

RESUMO

The constitutive heparin+ (HP) mast cells (MCs) in mice express mouse MC protease (mMCP)-5 and carboxypeptidase A (mMC-CPA). The amino acid sequence of mMCP-5 is most similar to that of human chymase-1, as are the nucleotide sequences of their genes and transcripts. Using a homologous recombination approach, a C57BL/6 mouse line was created that possessed a disrupted mMCP-5 gene. The resulting mice were fertile and had no obvious developmental abnormality. Lack of mMCP-5 protein did not alter the granulation of the IL-3/IL-9-dependent mMCP-2+ MCs in the jejunal mucosa of Trichinella spiralis-infected mice. In contrast, the constitutive HP+ MCs in the tongues of mMCP-5-null mice were poorly granulated and lacked mMC-CPA protein. Bone marrow-derived MCs were readily developed from the transgenic mice using IL-3. Although these MCs contained high levels of mMC-CPA mRNA, they also lacked the latter exopeptidase. mMCP-5 protein is therefore needed to target translated mMC-CPA to the secretory granule along with HP-containing serglycin proteoglycans. Alternately, mMCP-5 is needed to protect mMC-CPA from autolysis in the cell's granules. Fibronectin was identified as a target of mMCP-5, and the exocytosis of mMCP-5 from the MCs in the mouse's peritoneal cavity resulted in the expression of metalloproteinase protease-9, which has been implicated in arthritis. In support of the latter finding, experimental arthritis was markedly reduced in mMCP-5-null mice relative to wild-type mice in two disease models.


Assuntos
Artrite Experimental/patologia , Quimases/efeitos adversos , Mastócitos/enzimologia , Animais , Artrite Experimental/enzimologia , Artrite Experimental/etiologia , Carboxipeptidases A/análise , Carboxipeptidases A/deficiência , Carboxipeptidases A/metabolismo , Quimases/deficiência , Quimases/fisiologia , Humanos , Mastócitos/metabolismo , Mastócitos/patologia , Camundongos , Camundongos Endogâmicos C57BL , Vesículas Secretórias/metabolismo
15.
Ann Rheum Dis ; 77(6): 898-904, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29572291

RESUMO

OBJECTIVE: To determine whether a 2-week methotrexate (MTX) discontinuation after vaccination improves the efficacy of seasonal influenza vaccination in patients with rheumatoid arthritis (RA). METHODS: In this prospective randomised parallel-group multicentre study, patients with RA on stable dose of MTX were randomly assigned at a ratio of 1:1 to continue MTX or to hold MTX for 2 weeks after 2016-2017 quadrivalent seasonal influenza vaccine containing H1N1, H3N2, B-Yamagata and B-Victoria. The primary outcome was frequency of satisfactory vaccine response, defined as greater than or equal to fourfold increase of haemagglutination inhibition (HI) antibody titre at 4 weeks after vaccination against ≥2 of four vaccine strains. Secondary endpoints included seroprotection (ie, HI titre ≥1:40) rate, fold change in antibody titres. RESULTS: The modified intention-to-treat population included 156 patients in the MTX-continue group and 160 patients in the MTX-hold group. More patients in MTX-hold group achieved satisfactory vaccine response than the MTX-continue group (75.5% vs 54.5%, p<0.001). Seroprotection rate was higher in the MTX-hold group than the MTX-continue group for all four antigens (H1N1: difference 10.7%, 95% CI 2.0% to 19.3%; H3N2: difference 15.9%, 95% CI 5.9% to 26.0%; B-Yamagata: difference13.7%, 95% CI 5.2% to 22.4%; B-Victoria: difference 14.7%, 95% CI 4.5% to 25.0%). The MTX-hold group showed higher fold increase in their antibody titres against all four influenza antigens (all p<0.05). Change in disease activity was similar between groups. CONCLUSIONS: A temporary MTX discontinuation for 2 weeks after vaccination improves the immunogenicity of seasonal influenza vaccination in patients with RA without increasing RA disease activity. TRIAL REGISTRATION: NCT02897011.


Assuntos
Antirreumáticos/administração & dosagem , Artrite Reumatoide/tratamento farmacológico , Vacinas contra Influenza/imunologia , Influenza Humana/prevenção & controle , Metotrexato/administração & dosagem , Adulto , Idoso , Anticorpos Antivirais/biossíntese , Antirreumáticos/uso terapêutico , Artrite Reumatoide/imunologia , Desprescrições , Esquema de Medicação , Feminino , Humanos , Imunogenicidade da Vacina , Vírus da Influenza A/imunologia , Vacinas contra Influenza/efeitos adversos , Influenza Humana/imunologia , Betainfluenzavirus/imunologia , Masculino , Metotrexato/uso terapêutico , Pessoa de Meia-Idade , Estudos Prospectivos , Estações do Ano , Método Simples-Cego , Vacinação/efeitos adversos , Vacinação/métodos , Adulto Jovem
16.
Clin Exp Rheumatol ; 36(4): 627-635, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29465349

RESUMO

OBJECTIVES: Depression is more common in patients with systemic lupus erythematosus (SLE) compared to the general population. However, few studies have investigated risk factors of depression in SLE patients, and the results are inconsistent. This study evaluated the prevalence of, and risk factors for, depression in ethnically homogeneous Korean SLE patients. METHODS: In this study, 505 consecutive SLE patients were enrolled from the Korean Lupus Network registry. Demographic variables, clinical manifestations, laboratory findings, physician global assessment, and SLEDAI-2000 and SLICC damage index were recorded at enrolment. Patients were identified as having depressive symptoms using the Korean version of the Beck Depression Inventory (BDI) with a cut-off ≥16, and categorised into four groups. Multivariable logistic regression analyses were performed to identify independent risk factors for depression defined as a BDI score ≥16. RESULTS: Of the 505 patients, 97 (19.2%) were diagnosed with depression. Patients with a higher BDI score were older, more likely to be a current smoker, and had a SLICC score >1. Conversely, they had lower income and educational levels. Regarding the serologic findings, patients with a higher BDI score had lower anti-double-stranded DNA positivity and higher anticardiolipin (aCL) positivity. On multivariate analysis, the following factors were associated with depression: current smoking status (OR 2.533, p=0.049), aCL-positivity (OR 2.009, p=0.035), and a SLICC damage index score >1 (OR 2.781, p=0.039). On the other hand, high-level education (OR 0.253, p=0.024) and a high income (OR 0.228, p=0.008) were negatively associated with depression. CONCLUSIONS: Our results show that depression is prevalent in patients with SLE and multiple factors are associated with depression in SLE. These data could help guide target programmes for those at high risk of depression in SLE.


Assuntos
Anticorpos Anticardiolipina/sangue , Depressão/etiologia , Lúpus Eritematoso Sistêmico/psicologia , Classe Social , Adulto , Depressão/epidemiologia , Feminino , Humanos , Lúpus Eritematoso Sistêmico/imunologia , Masculino , Pessoa de Meia-Idade , Prevalência , Sistema de Registros
17.
Qual Life Res ; 27(1): 105-113, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-28831690

RESUMO

PURPOSE: This study assessed the relationships among the risk factors for and components of metabolic syndrome (MetS) and health-related quality of life (HRQOL) in a hypothesized causal model using structural equation modeling (SEM) in patients with systemic lupus erythematosus (SLE). METHODS: Of the 505 SLE patients enrolled in the Korean Lupus Network (KORNET registry), 244 had sufficient data to assess the components of MetS at enrollment. Education level, monthly income, corticosteroid dose, Systemic Lupus Erythematosus Disease Activity Index, Physicians' Global Assessment, Beck Depression Inventory, MetS components, and the Short Form-36 at the time of cohort entry were determined. SEM was used to test the causal relationship based on the Analysis of Moment Structure. RESULTS: The average age of the 244 patients was 40.7 ± 11.8 years. The SEM results supported the good fit of the model (χ 2 = 71.629, p = 0.078, RMSEA 0.034, CFI 0.972). The final model showed a direct negative effect of higher socioeconomic status and a positive indirect effect of higher disease activity on MetS, the latter through corticosteroid dose. MetS did not directly impact HRQOL but had an indirect negative impact on it, through depression. CONCLUSIONS: In our causal model, MetS risk factors were related to MetS components. The latter had a negative indirect impact on HRQOL, through depression. Clinicians should consider socioeconomic status and medication and seek to modify disease activity, MetS, and depression to improve the HRQOL of SLE patients.


Assuntos
Depressão/etiologia , Lúpus Eritematoso Sistêmico/complicações , Síndrome Metabólica/complicações , Qualidade de Vida/psicologia , Adulto , Estudos de Coortes , Feminino , Humanos , Lúpus Eritematoso Sistêmico/patologia , Masculino , Síndrome Metabólica/patologia , Estudos Prospectivos , Projetos de Pesquisa , Fatores de Risco
18.
Rheumatol Int ; 38(9): 1651-1660, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-30030624

RESUMO

This study compared the performance of the newly proposed 2016 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) criteria to the 2002 American-European Consensus Group (AECG) and 2012 ACR classification criteria for primary Sjogren's syndrome (pSS) in well-characterized Korean patients. Patients with pSS from 12 university-affiliated hospitals in Korea were enrolled from October 2013 to January 2017. Clinical and laboratory data were reviewed. For the validation set, patients who underwent evaluation tests to rule out pSS at Seoul St. Mary's hospital from November 2016 to December 2017 were analyzed. Baseline registry data were available in 458 patients, and 328 patients had sufficient data to determine the fulfillment of each criteria set. All three sets of criteria were met by 307 patients (93.6%). The newly proposed 2016 ACR/EULAR criteria were met by 325 patients (99.1%). The 2002 AECG and 2012 ACR criteria were met by 325 (99.1%) and 310 patients (94.5%), respectively. In a validation cohort consisting of 161 patients with pSS-related symptoms/signs, the sensitivity and specificity of the 2016 ACR/EULAR criteria were 100% [95% confidence interval (CI), 96.11-100.00] and 81.8% [95% CI, 76.15-94.26], respectively. Agreement between the 2016 criteria and 2012 or 2002 criteria was high (Cohen's kappa 0.736 and 0.769, respectively). The newly proposed 2016 ACR/EULAR criteria were met by most patients diagnosed with pSS according to previous criteria and showed higher sensitivity and lower specificity compared with both previous criteria sets.


Assuntos
Síndrome de Sjogren/classificação , Síndrome de Sjogren/diagnóstico , Europa (Continente) , Humanos , Estudos Prospectivos , República da Coreia , Reumatologia , Sensibilidade e Especificidade , Sociedades Médicas , Estados Unidos
19.
J Korean Med Sci ; 32(12): 1967-1973, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29115078

RESUMO

Gout attacks are often accompanied by systemic inflammatory response. The aim of the retrospective study was to compare gout patients in different age groups in terms of their clinical features at gout attacks. Patients, who were treated for gout attack in two tertiary medical centers between January 2000 and April 2014, were divided into young (≤ 50 years), middle-aged, and elderly (> 65 years) groups. Patients in three age groups were compared in terms of presence of fever (> 37.8°C), C-reactive protein (CRP) levels, and erythrocyte sedimentation ratio (ESR) at the gout attacks. Monocytes, which were isolated from 10 consecutive patients who previously experienced gout attacks, were stimulated with monosodium urate (MSU) crystals and cytokine production was measured by flow cytometry. Among 254 patients analyzed in this study, 48 were young, 65 were middle-aged, and 141 were elderly. The elderly patients were more likely to have fever (51.1%) during the attack than the young (20.8%) and middle-aged (30.8%) patients (P < 0.001 by χ² test). They were also more likely to have higher ESR and CRP levels than the young patients (P = 0.002 for ESR, P < 0.001 for CRP). Patients' age correlated significantly with CRP and ESR levels (both P < 0.001). After stimulation with MSU, the production of interleukin-1ß by monocytes increased with patients' age (r = 0.670, P = 0.03). In conclusion, gout attacks in elderly patients are associated with fever and higher ESR and CRP levels, often resembling a septic arthritis.


Assuntos
Gota/patologia , Adulto , Fatores Etários , Idoso , Sedimentação Sanguínea , Proteína C-Reativa/análise , Feminino , Febre/etiologia , Gota/diagnóstico , Gota/metabolismo , Humanos , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Masculino , Pessoa de Meia-Idade , Monócitos/citologia , Monócitos/metabolismo , Estudos Retrospectivos , Índice de Gravidade de Doença , Centros de Atenção Terciária , Fator de Necrose Tumoral alfa/metabolismo , Ácido Úrico/análise , Ácido Úrico/química
20.
Mod Rheumatol ; 27(5): 855-861, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27919202

RESUMO

OBJECTIVE: We investigated whether body mass index (BMI) is associated with parameters of disease activity and clinical manifestations in axial spondyloarthritis (axSpA). METHODS: Demographic, clinical, and radiological features and disease activity indexes from 789 axSpA patients (619 males and 170 females) were obtained from the Korean College of Rheumatology BIOlogics (KOBIO) registry. BMI (kg/m2) was classified into normal (BMI <23.0), overweight (23.0 ≤ BMI <25.0), and obese (BMI ≥25.0). Disease activity indexes included Bath ankylosing spondylitis disease activity index (BASDAI), erythrocyte sediment rate (ESR), C-reactive protein (CRP), and ankylosing spondylitis disease activity score (ASDAS). RESULTS: The mean BMI in patients with axSpA was 23.3 ± 3.5. 50.2% of all patients were overweight or obese. Overweight/obese patients had more syndesmophyte and less peripheral arthritis than those in normal BMI patients (p < 0.001 and p < 0.030, respectively). BMI was not associated with disease activity indexes in axSpA patients. Patients with syndesmophyte had higher BMI than those without syndesmophyte (24.2 ± 3.6 vs. 22.9 ± 3.3, p < 0.001). Multivariate logistic regression analysis showed that increased BMI was closely related with the presence of syndesmophyte (OR = 1.086, 95% CI 1.031-1.143, p = 0.002) Conclusions: Our results imply that increased BMI is significantly associated with the presence of syndesmophyte, but not with disease activity in axSpA.


Assuntos
Índice de Massa Corporal , Obesidade , Espondilartrite , Adulto , Proteína C-Reativa/análise , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/diagnóstico , Obesidade/epidemiologia , Obesidade/imunologia , Gravidade do Paciente , Radiografia/métodos , Sistema de Registros/estatística & dados numéricos , República da Coreia/epidemiologia , Fatores de Risco , Índice de Gravidade de Doença , Coluna Vertebral/diagnóstico por imagem , Espondilartrite/diagnóstico , Espondilartrite/epidemiologia , Espondilartrite/imunologia , Estatística como Assunto
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