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INTRODUCTION: Ixekizumab, an interleukin-17A inhibitor, was efficacious and well tolerated for the treatment of active radiographic axial spondyloarthritis (r-axSpA) in international clinical studies. This phase III study aimed to determine the efficacy and safety of ixekizumab for treating Chinese patients with active r-axSpA. METHODS: Adults with active r-axSpA naïve to biologic disease-modifying antirheumatic drugs (bDMARDs), or with an inadequate response/intolerance to one tumor necrosis factor inhibitor, were randomized (1:1), double-blind, to receive ixekizumab 80 mg every 4 weeks (IXEQ4W; starting dose 160 mg), or placebo, for 16 weeks. Patients receiving placebo were then switched to IXEQ4W, and those receiving IXEQ4W continued, until week 52. The primary endpoint was the proportion of bDMARD-naïve patients achieving an Assessment of SpondyloArthritis International Society 40 (ASAS40) response at week 16. RESULTS: In total, 147 patients were randomized to receive placebo (n = 73) or IXEQ4W (n = 74). At week 16, more bDMARD-naive patients achieved ASAS40 in the IXEQ4W group (n = 66; 40.9%) than the placebo group (n = 64, 7.8%; p < 0.001). In the overall study population, ASAS40 was also achieved by more patients in the IXEQ4W group (37.8%) than the placebo group (8.2%; p < 0.001) at week 16, with a significant difference observed as early as week 1. There were significant improvements in all key secondary endpoints at week 16 with IXEQ4W versus placebo. Efficacy was sustained at week 52 in patients who continued IXEQ4W and there were also clinical improvements from weeks 16 to 52 in patients switched to IXEQ4W. The safety profile of ixekizumab was consistent with that described previously. Infections and injection-site reactions were the most frequently reported events of special interest. CONCLUSIONS: IXEQ4W was associated with rapid and significant improvements in the signs and symptoms of active r-axSpA in Chinese patients at week 16 that were sustained at week 52, with no new safety signals. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov identifier: NCT04285229.
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Antirreumáticos , Espondiloartrite Axial , Espondilartrite , Adulto , Humanos , Resultado do Tratamento , Anticorpos Monoclonais Humanizados/efeitos adversos , Antirreumáticos/efeitos adversos , Espondilartrite/diagnóstico por imagem , Espondilartrite/tratamento farmacológico , Método Duplo-Cego , ChinaRESUMO
Objective: To enable physicians to understand the efficacy and safety of Tocilizumab (TCZ) in patients with severe coronavirus disease-2019 (COVID-19). Methods: We respectively reviewed the clinical records, laboratory results, and chest computed tomography (CT) scans of 5 geriatric patients with severe COVID-19 treated with TCZ during their inpatient hospitalization period in Wuhan from February 08, 2020 to April 04, 2020. The survival status of the patients in the third and the sixth month after being discharged was followed up and recorded. Results: On the fourteenth day after TCZ administration, periphery oxygen saturation rate (SpO2) returned to normal in 4 patients. The serum Interleukin-6 (IL-6) levels altered in five patients after TCZ infusion. One patient rapidly progressed to acute respiratory distress syndrome (ARDS) and died of multiple organ failures eventually. The other 4 patients were cured and discharged from the hospital. During the inpatient hospitalization period, two patients suffered from virus shedding periods (VSPs) delay, and one patient had mild upper respiratory tract infection. One patient died of esophageal carcinoma one month after being discharged. The other 3 patients survived despite mild cough and insomnia. Serum-specific IgG type antibody titer was decreased in one patient. Six months after being discharged, the other three patients were in good condition. Conclusion: TCZ may be an efficient therapeutic option for patients with COVID-19. However, the possibility of VSPs delay, secondary infection, serum protective antibody tilter attenuation, and long-term survival status should be addressed before TCZ therapy initiation.
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Objectives: A phase III, 24-weeks Chinese clinical trial demonstrated that efficacy and safety outcomes of treatments with 40 mg/0.8 ml HS016 (n = 416) or adalimumab (n = 232) for active ankylosing spondylitis (AS) patients was comparable. In the present study, a subanalysis of the clinical trial was conducted to determine whether also individual efficacy indicators were comparable between HS016 and adalimumab. Methods: The individual efficacy indicators total and nocturnal back pain, global assessment of disease activity, swollen joint count, Maastricht AS Enthesitis Score, Bath AS Disease Activity Index, Bath AS Functional Index, Bath AS Metrology Index and chest expansion, were assessed at baseline and every 2 weeks during the treatment period. Results: This subanalysis revealed no significant difference between the patient groups treated with HS016 or adalimumab for any individual efficacy indicator investigated at any time point (all p > 0.05) beside faster total back pain score improvements in the adalimumab group on week 10, 12 and 22, which became equal at week 24. Among these indicators, chest expansion showed a significant increase at each time point compared with baseline, whereas all other efficacy indicators showed significant decreases compared with baseline at each time point (all p < 0.05). All efficacy indicators had increased or decreased rapidly by week 2, and the values continued to increase/decrease up to week 12, with subsequent smaller changes thereafter up to week 24 of treatment. Conclusion: The response trajectory of most individual efficacy indicators was comparable between HS016 and adalimumab at each time point during the 24 weeks of the trial. Clinical Trial Registration: http://www.chictr.org.cn/showproj.aspx?proj=37910, identifier [ChiCTR1900022520].
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OBJECTIVE: The aim of this study was to evaluate the efficacy and safety of the biosimilar candidate of adalimumab (HS016) compared with adalimumab (Humira) for the treatment of active ankylosing spondylitis. METHODS: A multicenter, randomized, double-blind, parallel, positive control, phase III clinical trial was conducted at 28 locations in China. Patients with active ankylosing spondylitis were randomized in a 2:1 ratio to subcutaneously receive 40 mg of either HS016 or adalimumab every other week for 24 weeks. The primary endpoint was to achieve at least a 20% improvement (ASAS20) in patients at 24 weeks according to the Assessment of Spondyloarthritis International Society criteria. The secondary endpoint included other efficacy assessment parameters, health evaluations, safety, pharmacokinetic, and immunogenicity parameters. RESULTS: Following the random assignment of 648 patients into HS016 (n = 416) and adalimumab (n = 232) groups, no significant difference was found in the ASAS20 response rates at 24 weeks between the HS016 (364/416, 87.5%) and adalimumab (209/232, 90.1%) treatments and the difference between the response rates (- 2.59%; 90% confidence interval [CI] - 6.77 to 1.60) was within the predefined equivalence margin (± 15%). There were also no significant differences when the secondary endpoints were compared (all p > 0.05). Similarly, the rates of treatment-emergent adverse events (TEAEs) were not significantly different between the two groups, with most TEAEs being mild to moderate. Only nine severe cases were found, including seven within the HS016 group, three (0.7%) of which were tuberculosis cases. Plasma concentrations of HS016 and adalimumab from weeks 12 to 14 were similar during the steady-state period and steady-state maximal concentration (Cmax,ss) was equivalent for HS016 (7356.6 ng/mL) and adalimumab (7600.3 ng/mL). The accumulated proportion of patients with positive human anti-human antibodies (HAHAs) at week 24 was 326/412 (79.1%) in the HS016 group and 183/229 (79.9%) in the adalimumab group (p > 0.05), while the accumulated proportion of patients with positive neutralizing antibody (NAb) tests were 72/412 (17.5%) in the HS016 group and 43/229 (18.8%) in the adalimumab group (p > 0.05). CONCLUSION: HS016 resembled adalimumab in efficacy and safety over the 24-week treatment period. TRIAL REGISTRATION NUMBER: ChiCTR1900022520.
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Adalimumab/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Medicamentos Biossimilares/uso terapêutico , Espondilite Anquilosante/tratamento farmacológico , Adalimumab/efeitos adversos , Adalimumab/farmacocinética , Adulto , Anti-Inflamatórios/efeitos adversos , Anti-Inflamatórios/farmacocinética , Povo Asiático , Medicamentos Biossimilares/efeitos adversos , Medicamentos Biossimilares/farmacocinética , Método Duplo-Cego , Feminino , Humanos , Masculino , Índice de Gravidade de Doença , Equivalência Terapêutica , Resultado do Tratamento , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Fator de Necrose Tumoral alfa/imunologia , Adulto JovemRESUMO
Systemic sclerosis (SSc) is a complex autoimmune disease. The pathogenesis of SSc is currently unclear, although like other rheumatic diseases its pathogenesis is complicated. However, the ongoing development of bioinformatics technology has enabled new approaches to research this disease using microarray technology to screen and identify differentially expressed genes (DEGs) in the skin of patients with SSc compared with individuals with healthy skin. Publicly available data were downloaded from the Gene Expression Omnibus (GEO) database and intragroup data repeatability tests were conducted using Pearson's correlation test and principal component analysis. DEGs were identified using an online tool, GEO2R. Functional annotation of DEGs was performed using Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Finally, the construction and analysis of the proteinprotein interaction (PPI) network and identification and analysis of hub genes was carried out. A total of 106 DEGs were detected by the screening of SSc and healthy skin samples. A total of 10 genes [interleukin6, bone morphogenetic protein 4, calumenin (CALU), clusterin, cysteine rich angiogenic inducer 61, serine protease 23, secretogranin II, suppressor of cytokine signaling 3, Tolllike receptor 4 (TLR4), tenascin C] were identified as hub genes with degrees ≥10, and which could sensitively and specifically predict SSc based on receiver operator characteristic curve analysis. GO and KEGG analysis showed that variations in hub genes were mainly enriched in positive regulation of nitric oxide biosynthetic processes, negative regulation of apoptotic processes, extracellular regions, extracellular spaces, cytokine activity, chemoattractant activity, and the phosphoinositide 3 kinaseprotein kinase B signaling pathway. In summary, bioinformatics techniques proved useful for the screening and identification of biomarkers of disease. A total of 106 DEGs and 10 hub genes were linked to SSc, in particular the TLR4 and CALU genes.
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Biomarcadores/metabolismo , Escleroderma Sistêmico/genética , Escleroderma Sistêmico/metabolismo , Biologia Computacional/métodos , Redes Reguladoras de Genes/fisiologia , Humanos , Análise em Microsséries/métodos , Mapas de Interação de Proteínas/fisiologia , Transdução de Sinais/fisiologiaRESUMO
AIM: To investigate the potential therapeutic efficacy of iguratimod (IGU) on bleomycin (BLM)-induced pulmonary fibrosis in mice. METHODS: A total of 75 C57BL/6 mice were randomly and evenly divided into control group, BLM (5 mg/kg) group, BLM + IGU (90 mg/kg) group, BLM + methylprednisolone (MP, 10 mg/kg) group and BLM + pirfenidone (PF, 100 mg/kg) group. The mice were sacrificed on day 7, 14 and 28. The lung tissue was examined by hematoxylin and eosin staining and Masson staining to evaluate the degree of alveolitis and fibrosis, and serum cytokines were measured. RESULTS: Histopathological results showed that IGU attenuated BLM-induced alveolar inflammation and decreased collagen deposition in lung tissue from day 7 till day 28. Both the pathological alveolitis and fibrosis scores in the drug-treated groups (IGU group, MP group and PF group) were decreased dramatically compared with the BLM group on day 7, 14 and 28 (P < 0.05). There were no statistical significances among these three groups. Cytokine profile showed that IGU decreased the level of tumor necrosis factor-α (TNF-α), interleukin (IL)-1, IL-6 and matrix metalloproteinase (MMP)-9 which were up-regulated by BLM on day 7, 14 and 28 (P < 0.05). Furthermore, there is a strong correlation between the severity of pulmonary fibrosis and serum MMP-9 levels. CONCLUSION: IGU can decrease BLM-induced pulmonary fibrosis, and the anti-fibrotic effect of IGU is mediated partly via inhibition of MMP-9, which suggests that IGU could potentially be an effective therapeutic strategy for pulmonary fibrosis.
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Anti-Inflamatórios/farmacologia , Bleomicina , Cromonas/farmacologia , Colágeno/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Inibidores de Metaloproteinases de Matriz/farmacologia , Pneumonia/prevenção & controle , Alvéolos Pulmonares/efeitos dos fármacos , Fibrose Pulmonar/prevenção & controle , Sulfonamidas/farmacologia , Remodelação das Vias Aéreas/efeitos dos fármacos , Animais , Citocinas/sangue , Modelos Animais de Doenças , Mediadores da Inflamação/sangue , Masculino , Camundongos Endogâmicos C57BL , Pneumonia/induzido quimicamente , Pneumonia/enzimologia , Pneumonia/patologia , Alvéolos Pulmonares/enzimologia , Alvéolos Pulmonares/patologia , Fibrose Pulmonar/induzido quimicamente , Fibrose Pulmonar/enzimologia , Fibrose Pulmonar/patologiaRESUMO
AIM: To investigate the efficacy and safety of technetium-99 conjugated with methylene diphosphonate (99 Tc-MDP, Yunke Pharmaceutical industry) in the treatment of rheumatoid arthritis (RA). METHODS: A total of 120 patients with active RA were randomly divided into three groups: Group A (receiving oral meloxicam tablets); Group B (receiving intravenous drip of 99 TC-MDP); Group C (receiving combination treatment of intravenous drip of 99 Tc-MDP and oral meloxicam tablets). The main clinical and laboratory parameters were evaluated at baseline and after 14 days of therapy. RESULTS: After 14 days of treatment, American College of Rheumatology 20 response was 15.62%, 34.04% and 48.78% in the three groups, respectively. The incidence of adverse events in three groups were 3.13%, 8.51% and 9.76% respectly, and has no significant difference. In addition, biochemical markers of bone metabolism including bone alkaline phosphatase (BAP), tartrate resistant acid phosphatase (TRAP) and dickkopf-1 (DKK-1), all improved in the three groups, although more significant in Group B than Group A, and more significant in the combination group than monotherapy groups. CONCLUSION: 99 Tc-MDP has good efficacy and safety in the treatment of active RA patients; the benefit was more remarkable when 99 Tc-MDP was combined with NSAIDs. 99 Tc-MDP may also have potential to improve bone metabolism.
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Artrite Reumatoide/radioterapia , Remodelação Óssea/efeitos da radiação , Compostos Radiofarmacêuticos/administração & dosagem , Medronato de Tecnécio Tc 99m/administração & dosagem , Administração Oral , Adulto , Idoso , Anti-Inflamatórios não Esteroides/administração & dosagem , Artrite Reumatoide/sangue , Artrite Reumatoide/diagnóstico , Biomarcadores/sangue , China , Feminino , Humanos , Infusões Intravenosas , Masculino , Meloxicam , Pessoa de Meia-Idade , Compostos Radiofarmacêuticos/efeitos adversos , Medronato de Tecnécio Tc 99m/efeitos adversos , Tiazinas/administração & dosagem , Tiazóis/administração & dosagem , Fatores de Tempo , Resultado do Tratamento , Adulto JovemRESUMO
The aim of this study is to identify osteoarthritis (OA)-associated differentially methylated genes in human articular chondrocytes from patients with OA. DNA methylation profiling of articular chondrocytes from OA patients, rheumatoid arthritis (RA) patients, and controls was performed, and candidate genes were chosen for validation of gene demethylation status. The mRNA expression levels of candidate genes in chondrocytes were detected by real-time quantitative PCR. Chondrocytes from OA and RA group were treated with 5-Aza-2-deoxycytidine (5-Aza), and then the mRNA expression levels were detected. Forty-five genes with significant methylation differences between OA and control group were identified. Tumor necrosis factor receptor-associated factor 1 (TRAF1), connective tissue growth factor (CTGF), and chemokine (C-X3-C motif) ligand 1(CX3CL1) genes were hypomethylated in chondrocytes of OA and RA patients, which verified by bisulfite sequencing analysis. The mRNA expression level of TRAF1 and CTGF was significantly increased in OA and RA group (p < 0.05), while the expression level of CX3CL1 was only increased in OA group (p < 0.05). For the chondrocytes from OA and RA treated with 5-Aza, the mRNA expression level of TRAF1 and CTGF was highly increased (p < 0.05). It is the first time to show that TRAF1, CTGF, and CX3CL1 genes were hypomethylated in OA chondrocytes and have a consistent correlation with mRNA expression, which suggests that epigenetic changes in the methylation status of TRAF1, CTGF, and CX3CL1 contribute to the pathology of OA.
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Artrite Reumatoide/genética , Cartilagem Articular/metabolismo , Quimiocina CX3CL1/genética , Condrócitos/metabolismo , Fator de Crescimento do Tecido Conjuntivo/genética , Metilação de DNA , Osteoartrite/genética , Fator 1 Associado a Receptor de TNF/genética , Idoso , Idoso de 80 Anos ou mais , Azacitidina/análogos & derivados , Azacitidina/química , Células Cultivadas , Condrócitos/citologia , Decitabina , Epigênese Genética , Feminino , Humanos , Ligantes , Masculino , Pessoa de Meia-Idade , Osteoartrite/metabolismo , Domínios Proteicos , RNA Mensageiro/metabolismo , Tamanho da Amostra , Análise de Sequência de DNA , Tíbia/metabolismoRESUMO
OBJECTIVE: To evaluate the effects of a multitarget method involving plasmapheresis therapy combined with tumor necrosis factor (TNF)-α inhibitor and disease-modifying antirheumatic drugs (DMARDs) on disease activity parameters in the treatment of active rheumatoid arthritis (RA). METHODS: Sixty-five patients with active RA were divided into two groups according to the treatment administered: the plasmapheresis combination therapy group (Plasmapheresis combination group; 38 cases), in which patients received plasmapheresis therapy along with a TNF-α inhibitor (recombinant human tumor necrosis factor-Fc; rhTNFR:Fc; Etanercept biosimilars) and DMARDs, and a TNF-α inhibitor therapy group (biological agent group; 27 cases), in which patients received a TNF-α inhibitor and DMARDs. Clinical parameters were measured before and at 4 and 24 weeks after treatment. RESULTS: ACR20, ACR50, and ACR70 responses at week 4 were achieved in 84.2%, 78.9%, and 60.5% of the patients in the plasmapheresis combination group, respectively, and 74.1%, 55.6%, and 29.6% of the patients in the biological agent group, respectively. The ACR50 and ACR70 response rates were superior in the former than the latter group (p < 0.05). Similar patterns of statistical significance were observed for ACR20, ACR50, and ACR70 responses at week 24 after the treatment. ACR50 responses were achieved in 84.2% patients and ACR70 responses were achieved in 76.3% patients in the plasmapheresis combination group, and these proportions were better than those in the biological agent group (p < 0.05). CONCLUSIONS: The multitarget method combining plasmapheresis, TNF-α inhibitor, and DMARDs for RA therapy was superior to the combination of TNF-α inhibitor for reducing disease activity parameters in patients with active RA.
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Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Etanercepte/uso terapêutico , Plasmaferese/métodos , Adulto , Antirreumáticos/administração & dosagem , Antirreumáticos/efeitos adversos , Artrite Reumatoide/terapia , Terapia Combinada , Quimioterapia Combinada , Etanercepte/administração & dosagem , Etanercepte/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fator de Necrose Tumoral alfa/antagonistas & inibidoresRESUMO
Environmental factors play an important role in the development of rheumatoid arthritis (RA). Among these factors, smoking is generally considered to be an established risk factor for RA. Data regarding the impact of diet on risk of RA development is limited. This study assessed the impact of dietary patterns on RA susceptibility in Chinese populations. This was a large scale, case-control study composed of 968 patients with RA and 1037 matched healthy controls. Subjects were recruited from 18 teaching hospitals. Socio-demographic characteristics and dietary intakes 5 years prior to the onset of RA were reported by a self-administered questionnaire. Differences in quantity of consumption between cases and controls were analyzed by Student's t test. Multiple logistic regression analysis was applied to identify independent dietary risk factor(s) responsible for RA susceptibility. Compared to healthy individuals, RA patients had decreased consumption of mushrooms (P = 0.000), beans (P = 0.006), citrus (P = 0.000), poultry (P = 0.000), fish (P = 0.000), edible viscera (P = 0.018), and dairy products (P = 0.005). Multivariate analyses revealed that several dietary items may have protective effects on RA development, such as mushrooms (aOR = 0.669; 95%CI = 0.518-0.864, P = 0.002), citrus fruits (aOR = 0.990; 95%CI = 0.981-0.999, P = 0.04), and dairy products (aOR = 0.921; 95%CI 0.867-0.977, P = 0.006). Several dietary factors had independent effects on RA susceptibility. Dietary interventions may reduce the risk of RA.
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Artrite Reumatoide/epidemiologia , Dieta , Adulto , Idoso , Artrite Reumatoide/diagnóstico , Povo Asiático , Estudos de Casos e Controles , China/epidemiologia , Estudos Transversais , Progressão da Doença , Exposição Ambiental , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estado Nutricional , Análise de Regressão , Fatores de Risco , Fumar , Adulto JovemRESUMO
Randomized, controlled trials (RCTs) have assessed the effect of colchicine therapy in prevention of pericardial effusion (PE) and atrial fibrillation (AF). However, the effects are still inconclusive. PubMed, Cochrane Library, Google Scholar, and EMBASE database were searched. Primary outcome was the risk of PE and AF. Ten RCTs with 1981 patients and a mean follow-up of 12.6 months were included. Colchicine therapy was not associated with a significantly lower risk of post-operative PE (RR, 0.89; 95 % CI 0.70-1.13; p = 0.33, I (2) = 72.8 %) and AF (RR, 0.77; 95 % CI 0.52-1.13; p = 0.18, I (2) = 47.3 %). However, rates of pericarditis recurrence, symptoms persistence, and pericarditis-related hospitalization were significantly decreased with colchicine treatment. In addition, cardiac tamponade occurrence was similar between groups, and adverse events were significantly higher in the colchicine group. Colchicine may not significantly decrease the post-operative risk of PE and AF. However, only limited studies about patients undergoing cardiac surgery provide data about PE and AF.
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Fibrilação Atrial/prevenção & controle , Colchicina/farmacologia , Derrame Pericárdico/prevenção & controle , Fibrilação Atrial/tratamento farmacológico , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Procedimentos Cirúrgicos Cardíacos/estatística & dados numéricos , Distribuição de Qui-Quadrado , Colchicina/uso terapêutico , Humanos , Derrame Pericárdico/tratamento farmacológico , Pericardite/tratamento farmacológico , Pericardite/prevenção & controle , RecidivaRESUMO
Systemic lupus erythematosus (SLE) is an autoimmune disease with heterogeneous organ and system manifestations. In this study, urinary metabolic alterations related to SLE were investigated by performing gas chromatography/mass spectrometry (GC/MS) based metabolomics and multivariate statistical analysis. Patients with SLE and healthy controls could be clearly differentiated in view of the metabolic abnormity in urine. Among 70 identified endogenous metabolites, 23 metabolites were dramatically increased in SLE patients, which involved in several key metabolic pathways including energy metabolism, nucleotide metabolism, oxidative stress and gut-microbiome-derived metabolism. This noninvasive and GC/MS-based metabolomic technique is a promising and potent strategy for identifying novel biomarkers and understanding pathogenesis of SLE. Copyright © 2016 John Wiley & Sons, Ltd.
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Cromatografia Gasosa-Espectrometria de Massas/métodos , Lúpus Eritematoso Sistêmico/metabolismo , Lúpus Eritematoso Sistêmico/urina , Metaboloma , Metabolômica/métodos , Adolescente , Adulto , Biomarcadores/metabolismo , Biomarcadores/urina , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
OBJECTIVE: To evaluate the impact of RA on work capacity and identify factors related to work capacity impairment in patients with RA. METHODS: A cross-sectional multicentre study was performed in 21 tertiary care hospitals across China. A consecutive sample of 846 patients with RA was recruited, of which 589 patients of working age at disease onset constituted the study population. Information on the socio-demographic, clinical, working and financial conditions of the patients was collected. Logistic regression analyses were used to identify factors associated with work capacity impairment. RESULTS: The rate of work capacity impairment was 48.0% in RA patients with a mean disease duration of 60 months (interquartile range 14-134 months), including 11.7% leaving the labour force early, 33.6% working reduced hours and 2.7% changing job. Multivariable logistic regression analysis showed that reduced working hours was significantly related to current smoking [odds ratio (OR) 2.07 (95% CI 1.08, 3.97)], no insurance [OR 1.94 (95% CI 1.20, 3.12)], in manual labour [OR 2.66 (95% CI 1.68, 4.20)] and higher HAQ score [OR 2.22 (95% CI 1.36, 3.60)]. There was an association of current smoking [OR 3.75 (95% CI 1.54, 9.15)], in manual labour [OR 2.33 (95% CI 1.17, 4.64)], longer disease duration [OR 1.01 (95% CI 1.00, 1.01)] and lower BMI [OR 0.90 (95% CI 0.82, 0.99)] with leaving the labour force early. CONCLUSION: There is a substantial impact of RA on the work capacity of patients in China. Social-demographic, disease- and work-related factors are all associated with work capacity impairment.
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Artrite Reumatoide/epidemiologia , Artrite Reumatoide/fisiopatologia , Povo Asiático , Avaliação do Impacto na Saúde , Avaliação da Capacidade de Trabalho , Absenteísmo , Adulto , Idade de Início , Idoso , Artrite Reumatoide/etnologia , China/epidemiologia , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Análise de Regressão , Fatores SocioeconômicosRESUMO
OBJECTIVE: To investigate differences in genetic risk factors for rheumatoid arthritis (RA) in Han Chinese as compared with Europeans. METHODS: A genome-wide association study was conducted in China with 952 patients and 943 controls, and 32 variants were followed up in 2,132 patients and 2,553 controls. A transpopulation meta-analysis with results from a large European RA study was also performed to compare the genetic architecture across the 2 ethnic remote populations. RESULTS: Three non-major histocompatibility complex (non-MHC) loci were identified at the genome-wide significance level, the effect sizes of which were larger in anti-citrullinated protein antibody (ACPA)-positive patients than in ACPA-negative patients. These included 2 novel variants, rs12617656, located in an intron of DPP4 (odds ratio [OR] 1.56, P = 1.6 × 10(-21) ), and rs12379034, located in the coding region of CDK5RAP2 (OR 1.49, P = 1.1 × 10(-16) ), as well as a variant at the known CCR6 locus, rs1854853 (OR 0.71, P = 6.5 × 10(-15) ). The analysis of ACPA-positive patients versus ACPA-negative patients revealed that rs12617656 at the DPP4 locus showed a strong interaction effect with ACPAs (P = 5.3 × 10(-18) ), and such an interaction was also observed for rs7748270 at the MHC locus (P = 5.9 × 10(-8) ). The transpopulation meta-analysis showed genome-wide overlap and enrichment in association signals across the 2 populations, as confirmed by prediction analysis. CONCLUSION: This study has expanded the list of alleles that confer risk of RA, provided new insight into the pathogenesis of RA, and added empirical evidence to the emerging polygenic nature of complex trait variation driven by common genetic variants.
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Artrite Reumatoide/etnologia , Artrite Reumatoide/genética , Povo Asiático/genética , Dipeptidil Peptidase 4/genética , Peptídeos e Proteínas de Sinalização Intracelular/genética , Proteínas do Tecido Nervoso/genética , Receptores CCR6/genética , População Branca/genética , Adulto , Alelos , Artrite Reumatoide/epidemiologia , Estudos de Casos e Controles , Proteínas de Ciclo Celular , China/epidemiologia , Europa (Continente)/epidemiologia , Feminino , Predisposição Genética para Doença/etnologia , Predisposição Genética para Doença/genética , Estudo de Associação Genômica Ampla , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único/genética , Fatores de RiscoRESUMO
Primary Sjögren's syndrome is one of the most common autoimmune diseases. So far, genetic studies of Sjögren's syndrome have relied mostly on candidate gene approaches. To identify new genetic susceptibility loci for primary Sjögren's syndrome, we performed a three-stage genome-wide association study in Han Chinese. In the discovery stage, we analyzed 556,134 autosomal SNPs in 542 cases and 1,050 controls. We then validated promising associations in 2 replication stages comprising 1,303 cases and 2,727 controls. The combined analysis identified GTF2I at 7q11.23 (rs117026326: Pcombined = 1.31 × 10(-53), combined odds ratio (ORcombined) = 2.20) as a new susceptibility locus for primary Sjögren's syndrome. Our analysis also confirmed previously reported associations in Europeans in the regions of STAT4, TNFAIP3 and the major histocompatibility complex (MHC). Fine mapping of the region around GTF2I showed that rs117026326 in GTF2I had the most significant association, with associated SNPs extending from GTF2I to GTF2IRD1-GTF2I.
Assuntos
Proteínas de Ligação a DNA/genética , Peptídeos e Proteínas de Sinalização Intracelular/genética , Proteínas Nucleares/genética , Fator de Transcrição STAT4/genética , Síndrome de Sjogren/genética , Fatores de Transcrição TFII/genética , China , Cromossomos Humanos Par 7/genética , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Humanos , Complexo Principal de Histocompatibilidade/genética , Polimorfismo de Nucleotídeo Único , Proteína 3 Induzida por Fator de Necrose Tumoral alfaRESUMO
OBJECTIVE: To evaluate the safety of tumor necrosis factor-α (TNF-α) monoclonal antibody (infliximab) therapy in patients with rheumatoid arthritis (RA) and previous exposure to hepatitis B virus (HBV) who had normal liver function. METHODS: This is a retrospective study from a 26-week, prospective, multicenter trial in 234 patients with RA who received infusions of infliximab (3 mg/kg at week 0, 2, 6, 14 and 22). The medical records of these patients were reviewed, including the information on disease duration, laboratory tests and HBV markers. The data on liver function during the study was analyzed, as well as comparison between patients with previous exposure to HBV and patients without such exposure. RESULTS: Forty-one patients with previous exposure to HBV were HBsAg(-). Forty patients had normal alanine aminotransferase (ALT) and aspartate aminotransferase (AST) and only one patient with positive anti-HBc showed an elevated ALT level before administration of infliximab, and had a further increase of ALT level at week 14, but decreased thereafter. The average ALT and AST levels rose slightly during the treatment but remained in normal range and the differences were insignificant compared with baseline. There was no statistically significant difference in the incidence of liver function abnormalities during the treatment of infliximab between the patients with previous exposure to HBV and those without such exposure. CONCLUSION: In patients with RA and previous exposure to HBV but with a negative HBsAg and normal liver function at baseline, liver function abnormalities were not observed during infliximab treatment.
Assuntos
Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/epidemiologia , Vírus da Hepatite B , Hepatite B/epidemiologia , Adulto , Antirreumáticos/efeitos adversos , Antirreumáticos/uso terapêutico , Comorbidade , Feminino , Antígenos de Superfície da Hepatite B/sangue , Humanos , Infliximab , Rim/fisiologia , Fígado/enzimologia , Fígado/fisiopatologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Estudos Retrospectivos , Resultado do Tratamento , Fator de Necrose Tumoral alfa/antagonistas & inibidoresRESUMO
OBJECTIVE: To learn about the prevalence and risk factors of coronary artery disease (CAD) in rheumatoid arthritis (RA). METHODS: Data were obtained from a 12-month retrospective investigation of the patients with RA, randomly selected from Departments of Rheumatology and Immunology in 21 big hospitals in China. The data were collected about their social conditions, clinical conditions, medications associated with RA, such as disease modifying anti-rheumatic drugs (DMARDs), non steroidal anti-inflammatory drugs (NSAIDs), glucocorticoid, biologic agents. A nonparameter test and multivariate logistic regression analysis were performed. RESULTS: In the study, 960 patients were enrolled. The prevalence of CAD was 3.5% in China, which was obviously higher than that of normal people. The prevalence of overweight and obesity, smoking, hypertension, diabetes mellitus, hypercholesterolemia and cerebrovascular disease were 35.1%, 12.3%, 17.0%, 7.7%, 0.4% and 3.0%, respectively. Compared with the control group, the CAD group had higher age [(64.7±9.3) years vs. (52.3±14.0) years,P<0.001], more rheumatoid nodules (14.7% vs. 3.1%,P=0.005), lower rate of hydroxychloroquine (HCQ) use (5.9% vs. 22.6%,P=0.021), higher prevalence rates of lung interstitial disease (17.5% vs. 7.0%,P<0.001), diabetes mellitus and hypertension (29.4% vs. 7.0%,P<0.001; 38.2% vs. 16.2%,P=0.001). There was no obvious correlation of CAD in RA with joint deformity, rheumatoid factor (RF) titer, glucocorticoid use, hypercholesterolemia and body mass index (BMI). Multivariate analysis showed higher age, diabetes mellitus and hypertension were independent predictors of CAD, and the use of HCQ was a protective factor of CAD. CONCLUSION: The prevalence of CAD is 3.5%. Higher age, diabetes mellitus and hypertension are independent predictors of CAD, and the use of HCQ is a protective factor of CAD.
Assuntos
Artrite Reumatoide/complicações , Doença da Artéria Coronariana/complicações , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Criança , China/epidemiologia , Doença da Artéria Coronariana/epidemiologia , Diabetes Mellitus Tipo 2/complicações , Feminino , Humanos , Hipertensão/complicações , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores de Risco , Inquéritos e Questionários , Adulto JovemRESUMO
OBJECTIVE: To investigate the current status of tumor necrosis factor (TNF) inhibitors application in rheumatoid arthritis (RA) patients in China and to analyze the related factors. METHODS: A retrospective survey was conducted in 21 hospitals from different parts of China. The patients with RA were randomly enrolled. Data of their social backgrounds, clinical conditions, usage and adverse effects of TNF inhibitors were collected. The costs of TNF inhibitors and the indirect costs of the disease were calculated. A multivariate Logistic regression analysis was performed to analyze the factors related to TNF inhibitors application. RESULTS: In the study, 1 095 RA patients from July 2009 to November 2010 were enrolled, of whom 112 had received TNF inhibitors, representing 10.2% of the total patients. The patients who received etanercept and infliximab were 7.4% (86/1 095) of the patients and 2.4% (26/1 095), respectively. There were 0.5% of the patients (5/1 095) who had received both of the TNF inhibitors. The patients who had accepted etanercept and treatment duration for less than 3 months and 3-6 months accounted for 38.5% and 25.0% respectively, while those treated with Infliximab were 38.1%. Their health assessment questionnaire (HAQ) scores were 1.1, 0.5 and 0.1, corresponding to treatment duration of infliximab for less than 3, 3-6 and 6-9 months and those were 1.3, 1.0, 0.3 corresponding to treatment duration of etanercept, respectively. Infliximab costs were RMB 24 525.0, 69 300.0 and 96 800.0 Yuan and etanercept costs were RMB 7 394.8, 9 158.6, 54 910.9 Yuan, respectively. Indirect costs for RA patients who accepted infliximab for less than 3, 3-6 and 6-9 months were RMB 365.6, 0 and 158.9 Yuan and those who accepted etanercept were RMB 2 158.4, 288.5 and 180.1 Yuan, respectively. Allergy and infection were the main side-effects of etanercept and both happened in 3.5% of all the patients. Liver damage happened in 2.3% of all the patients, while allergy and infection happened in 6.5% of all the patients who accepted infliximab. Logistic regression analysis showed that patients with higher education experience increased the odds of entering the TNF inhibitors group (OR: 1.292, 95%CI: 1.132-1.473, P=0.000). CONCLUSION: About one-tenth of RA patients in China have accepted TNF inhibitors. Higher education experience is the key factor for using TNF inhibitors.
Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Honorários por Prescrição de Medicamentos/estatística & dados numéricos , Inibidores do Fator de Necrose Tumoral , Adulto , Idoso , Anti-Inflamatórios não Esteroides/economia , Anticorpos Monoclonais/economia , Anticorpos Monoclonais/uso terapêutico , Artrite Reumatoide/economia , China , Etanercepte , Feminino , Humanos , Imunoglobulina G/economia , Imunoglobulina G/uso terapêutico , Imunossupressores/economia , Imunossupressores/uso terapêutico , Infliximab , Masculino , Pessoa de Meia-Idade , Receptores do Fator de Necrose Tumoral/uso terapêutico , Estudos Retrospectivos , Inquéritos e QuestionáriosRESUMO
Lymphotoxin-alpha (LTA) gene has been reported to have a genetic association with systemic lupus erythematosus (SLE), psoriasis, and rheumatoid arthritis. However, the association of LTA with ankylosing spondylitis (AS) has not reported. By case-control study, we carried out the high density limited genome scanning to the HLA class III region about 58 kb in Ningxia population (case 300 and control 385). In this study, 33 SNPs in LTA were genotyped in Ningxia population. We analyzed these SNPs and the haplotypes covering LTA. Only the distribution of TCC haplotype which contains mutation allele of LTA rs909253 was statistically significant(P=0.0005). The C allele frequency of the LTA rs909253 T/C polymorphism was higher in AS cases than that in the controls (28.5% versus 19.7%, P=2×10-4) in Ningxia population. The results suggest that there is a relevance between LTA and the susceptibility of AS, and we identified that the LTA polymorphism may be associated with AS in Ningxia population.