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ID PMID Title PublicationDate abstract
27686126 Relationship between hsTnI and coronary stenosis in asymptomatic women with rheumatoid art 2016 Sep 29 BACKGROUND: Rheumatoid arthritis (RA) is a condition associated with accelerated progression of atherosclerosis in affected individuals. Myocardial assessment using exercise testing in such patients, however, is often difficult to perform. Our objective was to determine the factors associated with severe coronary stenosis using computed tomography (CT) angiography of the coronary arteries in asymptomatic patients with RA. METHODS: Forty-four women with RA were examined using CT angiography to detect atherosclerotic involvement and significant coronary stenosis (>50 %). CT findings were correlated with the cardiovascular risk score, and with classical and most recent parameters of atherosclerosis. RESULTS: CT angiography of the coronary arteries revealed severe stenosis (>70 %) in 9 % of patients. High-sensitivity troponin I level was associated with severe coronary stenosis (odds ratio 6.37; 95 % confidence interval 1.53 - 26.48; P = 0.011). Adjustment for confounders did not alter this result (P = 0.039). In contrast, classical and modified Systemic Coronary Risk Evaluation scores had no value in predicting severe stenosis (P ≥ 0.49). CONCLUSION: The present study showed the possible benefits of a coronary CT angiography in women with RA and asymptomatic ischemic coronary heart disease. Increased levels of high-sensitivity troponin I may be a potential indication for this type of examination. However, further studies are needed to confirm these results.
27014038 Intrinsic Brain Connectivity in Chronic Pain: A Resting-State fMRI Study in Patients with 2016 BACKGROUND: Rheumatoid arthritis (RA) is commonly accompanied by pain that is discordant with the degree of peripheral pathology. Very little is known about the cerebral processes involved in pain processing in RA. Here we investigated resting-state brain connectivity associated with prolonged pain in RA. METHODS: 24 RA subjects and 19 matched controls were compared with regard to both behavioral measures of pain perception and resting-resting state fMRI data acquired subsequently to fMRI sessions involving pain stimuli. The resting-state fMRI brain connectivity was investigated using 159 seed regions located in cardinal pain processing brain regions. Additional principal component based multivariate pattern analysis of the whole brain connectivity pattern was carried out in a data driven analysis to localize group differences in functional connectivity. RESULTS: When RA patients were compared to controls, we observed significantly lower pain resilience for pressure on the affected finger joints (i.e., P50-joint) and an overall heightened level of perceived global pain in RA patients. Relative to controls, RA patients displayed increased brain connectivity predominately for the supplementary motor areas, mid-cingulate cortex, and the primary sensorimotor cortex. Additionally, we observed an increase in brain connectivity between the insula and prefrontal cortex as well as between anterior cingulate cortex and occipital areas for RA patients. None of the group differences in brain connectivity were significantly correlated with behavioral parameters. CONCLUSION: Our study provides experimental evidence of increased connectivity between frontal midline regions that are implicated in affective pain processing and bilateral sensorimotor regions in RA patients.
26929654 Costs associated with rheumatoid arthritis in Italy: past, present, and future. 2016 This literature review examines available evidence on the current and past costs associated with rheumatoid arthritis (RA) in Italy, together with the future health-economic prospects for the disease. Studies have been conducted to date on the prevalence, or the associated costs, of RA in Italy. Although future changes in the incidence of RA are a matter of debate, the impact of RA on health care costs is expected to grow in coming decades in line with projected increases in life expectancy and in the proportion of elderly people in Italy. It has been estimated that the indirect (productivity loss and informal care) and intangible (deterioration in health-related quality of life) costs of the disease will contribute to an increase in national health service expenditure, which will correspond to 1% of the total health care costs of the nation in the near future. The introduction of biological agents for the treatment of rheumatic diseases has resulted in an increase in the direct costs of RA; however, economic analyses that exclude indirect costs will underestimate the full economic impact of RA. The effectiveness of innovative therapies in preventing disease progression and functional impairment may, over time, attenuate the cost impact of RA in terms of hospitalizations and work absenteeism. Further research is needed to develop estimates of the economic impact of different therapeutic approaches in patients with RA in Italy, in order to provide tools that can drive the choice of the most cost-effective therapeutic option while maintaining high-quality care.
25931742 Relation between functional ability and health-related quality of life of children with ju 2015 Mar [Purpose] The aim of this study was to assess patients' health-related quality of life, compare it with a healthy age-matched population, and examine associations between functional ability and quality of life among juvenile rheumatoid arthritis (JRA) patients. [Subjects and Methods] The study participants were 26 JRA patients and 25 controls. The Childhood Health Assessment Questionnaire and the Pediatric Quality of Life Inventory 4.0 Generic Core Scales were used to evaluate functional ability and health-related quality of life, respectively. [Results] Functional ability scores averaged 0.37 in the JRA group and 0.08 in the control group. There were significant between-group differences in functional ability scores in the overall cohort and in the subgroup of participants aged 14-16 years. Health-related quality of life scores were significantly lower in the JRA group than in the control group (68.39 vs. 85.17). In the JRA group, functional ability was statistically positively correlated with health-related quality of life. [Conclusion] We conclude that the mental state of adolescents with JRA affects their particular functional abilities. Subjects in the 14-16 age group who had a longer disease duration and higher difficulty scores showed a lower health-related quality of life than children in the other age groups.
26405544 Altered TNFAIP3 mRNA expression in peripheral blood mononuclear cells from patients with r 2015 Sep The tumor necrosis factor α-induced protein-3 (TNFAIP3) gene functions in negative immunoregulation and its single-nucleotide polymorphisms (SNPs) are associated with rheumatoid arthritis (RA) disease. However, its expression level in immune cells from RA patients remains unclear. The aim of the present study was to investigate whether the expression of TNFAIP3 is changed in patients with RA. Reverse transcription-quantitative polymerase chain reaction analysis was used to determine TNFAIP3 mRNA expression in peripheral blood mononuclear cells (PBMCs) from patients with RA and healthy controls. TNFAIP3 expression was decreased in RA patients compared with the healthy controls. The expression level of the TNFAIP3 gene negatively correlated with the RA score, anti-cyclic citrullinated peptide (CCP) antibody levels and C-reactive protein levels. Furthermore, RA patients with positive results of anti-CCP antibodies had a lower expression of TNFAIP3 than those without anti-CCP antibodies. In conclusion, the present results suggest that the insufficient expression of the TNFAIP3 gene in PBMCs may correlate with the diagnosis of RA.
26330803 Proteomics in Rheumatoid Arthritis Research. 2015 Aug Although rheumatoid arthritis (RA) is the most common chronic inflammatory autoimmune disease, diagnosis of RA is currently based on clinical manifestations, and there is no simple, practical assessment tool in the clinical field to assess disease activity and severity. Recently, there has been increasing interest in the discovery of new diagnostic RA biomarkers that can assist in evaluating disease activity, severity, and treatment response. Proteomics, the large-scale study of the proteome, has emerged as a powerful technique for protein identification and characterization. For the past 10 years, proteomic techniques have been applied to different biological samples (synovial tissue/fluid, blood, and urine) from RA patients and experimental animal models. In this review, we summarize the current state of the application of proteomics in RA and its importance in identifying biomarkers and treatment targets.
25657893 Host Responses in the Link Between Periodontitis and Rheumatoid Arthritis. 2015 Periodontitis and rheumatoid arthritis (RA) are common chronic inflammatory conditions and share many clinical and pathologic features. There is evidence to suggest that similar profiles of cytokine genotypes and their coding proteins are involved in the pathogenesis of periodontitis and RA. In particular, constitutive overproduction of pro-inflammatory cytokines, including tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6), has been implicated to play a pathologic role in the two inflammatory diseases. Results from studies with animal and human subjects have suggested an improvement of periodontal inflammatory condition after treatment with TNF-α inhibitors. Likewise, IL-6 receptor inhibition therapy has been suggested to have an effect on control of periodontal inflammation in patients with RA. In the present review, we provide an overview of studies showing the pathological role of cytokines in the linkage between periodontitis and RA, and further summarize the current studies assessing the effect of cytokine targeted therapy on periodontal condition.
27403334 Scintigraphic detection of TNF-driven inflammation by radiolabelled certolizumab pegol in 2016 BACKGROUND: Biologicals are the cornerstone for many treatment algorithms in inflammatory arthritis. While tumour necrosis factor (TNF) inhibitors may achieve important responses in ∼50% of patients with rheumatoid arthritis (RA) and spondyloarthritis (SpA), a significant fraction of patients are partial or non-responders. We hypothesised that in vivo assessment of TNF by scintigraphy with 99mTc-radiolabelled certolizumab pegol (CZP) might lead to a more 'evidence-based biological therapy'. OBJECTIVES: Our goal was to perform a proof-of-concept study of in vivo detection of TNF by immunoscintigraphy of a radiolabelled TNF inhibitor in RA and SpA, and correlate this with clinical, imaging findings and therapeutic outcome. METHODS: CZP was conjugated with succinimidyl-6-hydrazino-nicotinamide and subsequently radiolabelled with Tc99m. Whole body and static images of hands, feet and sacroiliac joints of 20 patients (5 RA; 15 SpA) were acquired at 3 time points. Immunoscintigraphic findings were scored semiquantitatively. Subsequently, all patients were treated with CZP. RESULTS: In peripheral joints, clinically affected joints or abnormal ultrasound findings were observed more frequently (p<0.001) in the scintigraphic-positive group. In patients with axial SpA, bone marrow edema on MRI was detected more frequently (p<0.001) in quadrants with tracer uptake. At the patient level, the odds of a joint remaining tender despite 24 weeks of CZP treatment was significantly smaller in joints with clear tracer uptake as compared with those with no uptake (OR=0.42, p=0.04). CONCLUSIONS: Immunoscintigraphy with radiolabelled CZP demonstrated both axial and peripheral inflammation, and displayed good correlation with clinical features, conventional imaging and therapy response. TRIAL REGISTRATION NUMBER: NCT01590966; Results.
25741185 Predictive factors related to the efficacy of golimumab in patients with rheumatoid arthri 2015 In order to investigate the predictive factors related to clinical efficacy and radiographic progression at 24 weeks by looking at the serum levels of tumor necrosis factor (TNF)-α and interleukin (IL)-6 including baseline characteristics in patients with rheumatoid arthritis (RA) treated with golimumab, serum concentrations of TNF-α and IL-6 were analyzed every 4 weeks up to 24 weeks in 47 patients treated with golimumab. Baseline levels of the Disease Activity Score 28 C-reactive protein (DAS28-CRP) and Simplified Disease Activity Index (SDAI) scores were also assessed. Radiographic progression using the van der Heijde-modified Sharp (vdH-S) score was assessed in 29 patients. Multiple regression analyses related to the DAS28-CRP score and delta total sharp score at 24 weeks was undertaken using the baseline characteristics of patients and serum concentrations of matrix metallo-proteinase (MMP)-3, TNF-α, and IL-6. The DAS28-CRP score and SDAI decreased significantly at 4 weeks up to 24 weeks compared with baseline. Serum levels of TNF-α were not changed significantly up to 24 weeks compared with baseline, but those of IL-6 decreased significantly at 4 weeks up to 8 weeks. Multiple regression analyses showed that disease duration and serum levels of MMP-3 were related significantly to the DAS28-CRP score at 24 weeks. Radiographic progression was related significantly to disease duration with regard to joint space narrowing and bone erosion. However, serum levels of TNF-α and IL-6 were not correlated significantly with the DAS28-CRP score and radiographic progression. These data suggest that decreasing serum levels of IL-6 significantly, MMP-3, and disease duration are predictive factors for RA activity in patients taking golimumab.
27642302 Whole-Genome Expression Analysis and Signal Pathway Screening of Synovium-Derived Mesenchy 2016 Synovium-derived mesenchymal stromal cells (SMSCs) may play an important role in the pathogenesis of rheumatoid arthritis (RA) and show promise for therapeutic applications in RA. In this study, a whole-genome microarray analysis was used to detect differential gene expression in SMSCs from RA patients and healthy donors (HDs). Our results showed that there were 4828 differentially expressed genes in the RA group compared to the HD group; 3117 genes were upregulated, and 1711 genes were downregulated. A Gene Ontology analysis showed significantly enriched terms of differentially expressed genes in the biological process, cellular component, and molecular function domains. A Kyoto Encyclopedia of Genes and Genomes analysis showed that the MAPK signaling and rheumatoid arthritis pathways were upregulated and that the p53 signaling pathway was downregulated in RA SMSCs. Quantitative real-time polymerase chain reaction was applied to verify the expression variations of the partial genes mentioned above, and a western blot analysis was used to determine the expression levels of p53, p-JNK, p-ERK, and p-p38. Our study found that differentially expressed genes in the MAPK signaling, rheumatoid arthritis, and p53 signaling pathways may help to explain the pathogenic mechanism of RA and lead to therapeutic RA SMSC applications.
26884918 Establishment of a cell model for screening antibody drugs against rheumatoid arthritis wi 2015 TNFα played a dominant role in the development and progression of rheumatoid arthritis (RA). Clinical trials proved the efficacies of anti-TNFα agents for curing RA. However, most researchers were concentrating on their abilities of neutralizing TNFα, the potencies of different anti-TNFα agents varied a lot due to the antibody-dependent cell-mediated cytotoxicity (ADCC) or complement dependent cytotoxicity (CDC). For better understanding and differentiating the potentiality of various candidate anti-TNF reagents at the stage of new drug research and development, present study established a cell model expressing the transmembrane TNFα for usage in in vitro ADCC or CDC assay, meanwhile, the assay protocol described here could provide guidelines for screening macromolecular antibody drugs. A stable cell subline bearing transmembrane TNFα was first established by conventional transfection method, the expression of transmembrane TNFα was approved by flow cytometer, and the performance of the stable subline in ADCC and CDC assay was evaluated, using human peripheral blood mononuclear cells as effector cells, and Adalimumab as the anti-TNFα reagent. The stable cell subline demonstrated high level of surface expression of transmembrane TNFα, and Adalimumab exerted both ADCC and CDC effects on this cell model. In conclusion, the stable cell line we established in present research could be used in ADCC or CDC assay for screening antibody drugs, which would provide in-depth understanding of the potencies of candidate antibody drugs in addition to the traditional TNFα neutralizing assay.
26618109 Disease control by regulation of P-glycoprotein on lymphocytes in patients with rheumatoid 2015 Nov 20 The main purpose of treatment of rheumatoid arthritis (RA) with disease modifying antirheumatic drugs (DMARDs) is to control activation of lymphocytes, although some patients do not respond adequately to such treatment. Among various mechanisms of multidrug resistance, P-glycoprotein (P-gp), a member of ATP-binding cassette transporters, causes drug-resistance by efflux of intracellular drugs. Certain stimuli, such as tumor necrosis factor-α, activate lymphocytes and induce P-gp expression on lymphocytes, as evident in active RA. Studies from our laboratories showed spontaneous nuclear accumulation of human Y-box-binding protein-1, a multidrug resistance 1 transcription factor, in unstimulated lymphocytes, and surface overexpression of P-gp on peripheral lymphocytes of RA patients with high disease activity. The significant correlation between P-gp expression level and RA disease activity is associated with active efflux of drugs from the lymphocyte cytoplasm and in drug-resistance. However, the use of biological agents that reduce P-gp expression as well as P-gp antagonists (e.g., cyclosporine) can successfully reduce the efflux of corticosteroids from lymphocytes in vitro, suggesting that both types of drugs can be used to overcome drug-resistance and improve clinical outcome. We conclude that lymphocytes activated by various stimuli in RA patients with highly active disease acquire P-gp-mediated multidrug resistance against corticosteroids and probably some DMARDs, which are substrates of P-gp. Inhibition/reduction of P-gp could overcome such drug resistance. Expression of P-gp on lymphocytes is a promising marker of drug resistance and a suitable therapeutic target to prevent drug resistance in patients with active RA.
26494481 Ocular Involvement in Systemic Autoimmune Diseases. 2015 Dec Eye involvement represents a common finding in patients with systemic autoimmune diseases, particularly rheumatoid arthritis, Sjogren syndrome, seronegative spondyloarthropathy, and antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis. The eye is a privileged immune site but commensal bacteria are found on the ocular surface. The eye injury may be inflammatory, vascular or infectious, as well as iatrogenic, as in the case of hydroxychloroquine, chloroquine, corticosteroids, and bisphosphonates. Manifestations may affect different components of the eye, with episcleritis involving the episclera, a thin layer of tissue covering the sclera; scleritis being an inflammation of the sclera potentially leading to blindness; keratitis, referring to corneal inflammation frequently associated with scleritis; and uveitis as the inflammation of the uvea, including the iris, ciliary body, and choroid, subdivided into anterior, posterior, or panuveitis. As blindness may result from the eye involvement, clinicians should be aware of the possible manifestations and their management also independent of the ophthalmologist opinion as the therapeutic approach generally points to the underlying diseases. In some cases, the eye involvement may have a diagnostic implication, as for episcleritis in rheumatoid arthritis, or acute anterior uveitis in seronegative spondyloarthritis. Nonetheless, some conditions lack specificity, as in the case of dry eye which affects nearly 30 % of the general population. The aim of this review is to elucidate to non-ophthalmologists the major ocular complications of rheumatic diseases and their specific management and treatment options.
27708927 Sarcopenia in women with rheumatoid arthritis. 2015 Jun OBJECTIVE: To assess sarcopenia status in women with rheumatoid arthritis (RA). MATERIAL AND METHODS: Thirty female patients with RA and 30 female controls without RA were enrolled in this study. Sarcopenia status in patients with RA was evaluated by assessing body composition using dual X-ray absorptiometry (DXA). C-reactive protein (CRP) levels and erythrocyte sedimentation rate (ESR) were measured, and body mass index (BMI) and Disease Activity Score (DAS28) were calculated. Because sarcopenia differs between men and women, the study groups comprised only females. RESULTS: It was found that skeletal muscle index (SMI) was lower in patients with RA (5.83±0.807) than in controls (7.30±1.640). Sarcopenia (in females with an SMI of ≤5.75 kg/m(2)) was more common in the RA group and the difference was statistically significant (p=0.004). Sarcopenia was more common in patients with RA who were normal or overweight than in those who were obese according to their BMI. There was no relationship between sarcopenia and DAS28 in the RA group (p=0.530), whereas CRP levels were significantly higher in patients with sarcopenia (p=0.230). No relationship was found between drug use and sarcopenia in the RA group. CONCLUSION: It was found that SMI was decreased and sarcopenia risk was elevated in patients with RA and the risk was higher in non-obese patients.
26002455 Pro-oxidant- Antioxidant Balance (PAB) in Rheumatoid Arthritis and its Relationship to Dis 2015 BACKGROUND: Rheumatoid arthritis (RA) is an autoimmune disease that tends to be progressive and chronic. Previous studies showed that oxidative stress has a main role in pathology of RA. The aim of this study was the easy elucidation of oxidative stress through pro-oxidant-antioxidant balance (PAB) in these patients. METHOD: The sera of 130 RA patients and 130 age-matched healthy subjects (HS) were collected and the PAB was measured. According to the normal value of PAB in HS, the patients were divided into two groups; patients with increased serum PAB and those with normal serum PAB values. In patients with increased PAB value, the correlation of PAB value with RA disease activity [(DAS28ESR)], biochemical parameters, and BMI were determined. RESULTS: Significantly higher serum PAB values were found in the whole RA group of patients (88.69±39.42 HK) in comparison to HS (53.57±25.10 HK), p . 0.05. There was no significant correlation between PAB values and RA disease activity. In patients with elevated serum PAB value; serum cholesterol, triglycerides and BMI were significantly higher in comparison to patients with normal values. CONCLUSION: The PAB test can show the oxidative stress in RA patients. Further research should be done to determine the potency of the PAB assay as a tool for monitoring adverse effect of oxidative stress in RA, as well as the effect of antioxidant therapies in the outcomes.
25995597 Aerobic exercise improves oxidant-antioxidant balance in patients with rheumatoid arthriti 2015 Apr [Purpose] Although oxidative stress is known to be present in rheumatoid arthritis (RA), the effects of exercise on oxidative parameters are unknown. The aim of this study was to investigate the effects of acute aerobic exercise on serum oxidant and antioxidant levels in patients with RA. [Subjects and Methods] Sixteen patients with RA and 10 age-matched healthy volunteers participated in this study. All participants wore polar telemeters and walked on a treadmill for 30 minutes at a speed eliciting 60-75% of maximal heart rates. Blood samples were obtained before, immediately and 24 hours after exercise and malondialdehyde (MDA) and total sulfhydrile group (RSH) levels were measured. [Results] Both groups had similar heart rates during the test but the treadmill speed of the RA patients was significantly lower than that of the healthy volunteers. Serum MDA levels were lower than in both groups immediately after exercise, with greater decrements in the RA patients than controls. MDA levels returned to baseline 24 hours after the exercise only in the controls; they remained low in the RA patients. There was a slight increase in serum RSH levels after exercise compared to baseline in both groups. [Conclusion] Moderate intensity treadmill exercise did not have any adverse effect on the oxidant-antioxidant balance. The results suggest that such an exercise may be safely added to the rehabilitation program of RA for additional antioxidant effects. Morever, this antioxidant environment is maintained longer in RA patients.
25694859 Drug free remission after steroid-dependent disappearance of lymphoproliferative disorder 2015 INTRODUCTION: TNF-α inhibitors plus MTX appear to have benefit in the longer-term reduction of RA. Boolean long-term remission under drug-free conditions is rare. The therapeutic mechanism and the factor of predicting response have not been clarified yet. CASE DESCRIPTION: A 24-year-old female rheumatoid arthritis (RA) patient, who once attained complete remission (CR) with the combination therapy with tumor necrosis factor alpha (TNF-alpha) inhibitor adalimumab (ADA) and methotrexate (MTX), showed the occurrence of Epstain- Barr virus (EBV)-associated lymphoproliferative disorder (LPD). Pulse treatment with methylprednisolone after the termination of anti TNF-α therapy resulted in the remission of EBV-associated LPD. The administration of prednisolone (PSL) was tapered off after the improvement of clinical symptoms and laboratory data. The patients achieved drug-free 12 months after urgent hospitalization and delivered healthy baby 2 years after hospital discharge. She has been complete drug-free Boolean remission for 5 years. DISCUSSION AND EVALUATION: The purpose of this brief case is report that we experienced the remission of LPD after CR with combined therapy with ADA and MTX. We believe this case report will be one of the paths for unveiling the pathogenesis and improving the treatment for RA. CONCLUSIONS: We believe this case report will be one of the paths for unveiling the pathogenesis and improving the treatment for RA.
27279757 Up-to-Date Information on Rheumatoid Arthritis-Associated Interstitial Lung Disease. 2015 Pulmonary involvement is common in rheumatoid arthritis (RA) and affects all the components of the lung. Interstitial lung disease (ILD) is the most predominant pulmonary manifestation and has been identified as the main cause of morbidity and mortality in RA. Clinically significant RA-ILD occurs in approximately 10% of RA patients. Several risk factors, such as old age, male gender, and smoking, have been reported to date. Histologically, the proportion of the usual interstitial pneumonia (UIP) pattern is higher in RA-ILD than in ILD associated with other connective tissue diseases, and RA-ILD also shows nonspecific interstitial pneumonia and organizing pneumonia patterns. High-resolution computed tomography scans are highly predictive of the histological UIP pattern with a specificity of 96%-100%. Acute exacerbation, which is the acute deterioration of the respiratory status characterized by newly developed bilateral infiltrates with unknown etiologies, has been reported in RA-ILD. Although acute exacerbation of RA-ILD has high mortality, similar to that of idiopathic pulmonary fibrosis, its incidence is lower in RA-ILD than in idiopathic pulmonary fibrosis. A consensus treatment has not yet been established. Current therapeutic regimens typically include corticosteroids with or without cytotoxic agents. Recent large longitudinal studies reported that the prognosis of RA-ILD was poor with a median survival of 2.6-3.0 years. Furthermore, histological and/or radiological patterns, such as UIP or non-UIP, have significant prognostic implications. RA-ILD patients with histological or radiological UIP patterns have poorer prognoses than those with non-UIP patterns. This review assessed the characteristics of RA-ILD by overviewing recent studies in the field and focused on the clinical significance of histological and/or radiological patterns in RA-ILD.
26131115 Association between CCR6 and rheumatoid arthritis: a meta-analysis. 2015 OBJECTIVE: Chemokine (C-C motif) receptor 6 gene (CCR6) polymorphism has been reported to be associated with rheumatoid arthritis (RA) in different ethnic populations. Moreover, its inhibition by monoclonal antibody in mouse model has suppressed arthritis. However, few replication studies have reported conflicting results about this association. Therefore, to establish that CCR6 indeed is a risk factor associated with RA among different ethnic populations, a comprehensive meta-analysis study was conducted. METHODS: PubMed and MEDLINE databases were searched using the term 'CCR6' for all articles published before May 2014. All the replication studies examining the association between CCR6 and RA were reviewed for meta-analysis. Data were summarized using random-effects meta-analysis. The heterogeneity and publication bias among studies were examined by χ(2) -based Q statistic test and Egger's test, respectively. RESULTS: A total of 24955 RA patients and 56129 controls from seven articles were included in the meta-analysis. While CCR6 was a risk factor in Asian (OR = 1.19, 95% CI: 1.14-1.24) and European (OR = 1.14, 95% CI: 1.08-1.21) populations, it was indicated as a protective factor in African Americans (OR = 0.79, 95% CI: 0.62-0.96). CONCLUSIONS: Our meta-analysis study concludes that there is a significant association between CCR6 and RA in all racial groups except African-American subgroup, which require a large sample size for concrete prediction.
26059273 Methods for treating IL-6-related diseases (US2015010554A1): a patent evaluation. 2015 INTRODUCTION: IL-6 is involved in a variety of diseases such as acute or chronic inflammation and autoimmune diseases, and the modulation of IL-6 level is recognized as an important target. Therefore, the blocking agent of IL-6 receptor (IL-6R), particularly anti-IL-6R antibody, was invented and its clinical efficacy was well resolved. However, it has not been shown that synergistic effects can be achieved by the combination of anti-IL-6R antibody with immunosuppressants. AREAS COVERED: This patent assessed the possible use of anti-IL-6R antibody (tocilizumab) plus methotrexate (MTX) for the treatment of acute or chronic inflammatory diseases and autoimmune diseases including nephritis, Crohn's disease, ulcerative colitis, pancreatitis, juvenile idiopathic arthritis, rheumatoid arthritis, and psoriasis. A large Phase II trial of tocilizumab to determine the optimum dose of tocilizumab alone and in combination with MTX for the treatment of rheumatoid arthritis was carried out and its result was analyzed. In conclusion, the combination use of tocilizumab plus MTX was confirmed as clinically effective and safe for the treatment of rheumatoid arthritis whereas substantial evidence regarding superiority to tocilizumab monotherapy is still lacking. EXPERT OPINION: To prove synergistic effect or enhancement of tocilizumab plus MTX therapy, more diverse diseases related to IL-6 and tocilizumab therapy, not limited to rheumatoid arthritis, have to be evaluated, along with its safety.