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ID PMID Title PublicationDate abstract
27698108 Definition for Rheumatoid Arthritis Erosions Imaged with High Resolution Peripheral Quanti 2016 Oct OBJECTIVE: High-resolution peripheral quantitative computed tomography (HR-pQCT) sensitively detects erosions in rheumatoid arthritis (RA); however, nonpathological cortical bone disruptions are potentially misclassified as erosive. Our objectives were to set and test a definition for pathologic cortical bone disruptions in RA and to standardize reference landmarks for measuring erosion size. METHODS: HR-pQCT images of metacarpophalangeal joints of RA and control subjects were used in an iterative process to achieve consensus on the definition and reference landmarks. Independent readers (n = 11) applied the definition to score 58 joints and measure pathologic erosions in 2 perpendicular multiplanar reformations for their maximum width and depth. Interreader reliability for erosion detection and variability in measurements between readers [root mean square coefficient of variation (RMSCV), intraclass correlation (ICC)] were calculated. RESULTS: Pathologic erosions were defined as cortical breaks extending over a minimum of 2 consecutive slices in perpendicular planes, with underlying trabecular bone loss and a nonlinear shape. Interreader agreement for classifying pathologic erosions was 90.2%, whereas variability for width and depth erosion assessment was observed (RMSCV perpendicular width 12.3%, axial width 20.6%, perpendicular depth 24.0%, axial depth 22.2%; ICC perpendicular width 0.206, axial width 0.665, axial depth 0.871, perpendicular depth 0.783). Mean erosion width was 1.84 mm (range 0.16-8.90) and mean depth was 1.86 mm (range 0.30-8.00). CONCLUSION: We propose a new definition for erosions visualized with HR-pQCT imaging. Interreader reliability for erosion detection is good, but further refinement of selection of landmarks for erosion size measurement, or automated volumetric methods, will be pursued.
27692390 Sensitivity and specificity of assessment instruments of quality of life in rheumatoid art 2016 Sep OBJECTIVE: To check sensitivity and specificity of assessment instruments of QoL in patients with rheumatoid arthritis (RA). METHODOLOGY: Accuracy study in a sample consisting of patients with confirmed diagnosis of RA. QoL questionnaires QV SF-36 (Gold Standard), HAQ and NHP were applied. The Pearson correlation coefficient, ROC curve, AUC and Youden Index (J) were used to analyze the data. RESULTS: This study enrolled 97 individuals with RA. The functional capacity estimated by SF-36 was correlated with the total score of HAQ (r=-0.666; p<0.001; J=0.579), while the emotional aspects of SF-36 were correlated with the emotional reactions domain of NHP (r=-0.316; p=0.005; J=0.341). The vitality domain of SF-36 was correlated with the level of energy of NHP (r=-0.362; p=0.001; J=0.302). For the evaluation of functional capacity (AUC=0.839; p<0.001) and physical aspect (AUC=0.755; p<0.001) the most accurate instrument was the HAQ. For evaluation of the impact of vitality, sleep (AUC=0.679; p=0.007), emotional reactions (AUC=0.674; p=0.009) and level of energy in QoL, the NHP (AUC=0.633; p=0.045) was the most specific and sensitive. In the evaluation of the emotional aspect domain, the most accurate instrument was the NHP in the "emotional reaction" score (AUC=0.699; p=0.003). The evaluation of pain was limited in the three instruments and SF-36 was the only one in assess of the domains of social aspects and general health status. CONCLUSION: For evaluation of the physical aspects in patients with RA, the HAQ is the most accurate. For evaluation of emotional aspects the NHP is the most indicated, although the SF-36 was the only one in the evaluation of general domains.
26781783 Determinants of methotrexate adherence in rheumatoid arthritis patients. 2016 May In rheumatoid arthritis (RA) patients, weekly intake of methotrexate (MTX) is the basic drug treatment. This observational study aims to investigate how many RA patients are adherent in terms of MTX intake and to identify determinants of non-adherence. Intake of MTX (orally or via injection) was recorded in 129 RA patients with an electronic monitoring system (MEMS(®)) during 16 weeks. In addition, two adherence questionnaires, the Medication Adherence Report Scale (MARS-5) and the Compliance-Questionnaire-Rheumatology (CQR) as well as a visual analogue scale (VAS) measuring MTX adherence, were administered to these patients. As possible determinants of adherence, data on demographics, disease and treatment characteristics, depression, illness cognitions, motivation, and social support were collected. Of all participants, 58 % were fully adherent and 75 % skipped at most one dose during 16 weeks. A better mental health status and suffering from comorbidities had a positive effect on adherence, while living alone had a negative effect. These three predictors explained 30 % of the variance in MTX adherence. Of the three self-report medication adherence measures, the VAS correlated the highest with the results of the electronic monitoring system (r = 0.552, p = 0.01). A relatively high adherence rate was observed in RA patients treated with MTX. The determinants identified by this study could be used to screen patients at risk for non-adherence. A simple VAS scale seems to be an acceptable way for a preliminary screening of MTX adherence.
26581918 The Association Between Serum Selenium Levels with Rheumatoid Arthritis. 2016 Jul There are conflicting reports on the correlation between serum selenium (Se) levels with rheumatoid arthritis (RA). Through a meta-analysis approach, the aim of the present study is to clarify the relationship between serum Se levels with RA. We searched literatures that met our predefined criteria in PubMed, ScienceDirect, and OVID published as of September 2015. Ten eligible articles with 14 case-control studies involving 716 subjects were identified. Overall, pooled analysis indicated that subjects with RA had lower serum levels of Se than the healthy controls (standardized mean difference (SMD) = -1.347, 95 % confidence interval (CI) = [-1.872, -0.823], p < 0.001). Further subgroup analysis indicated that subjects with RA had lower serum Se levels than healthy controls in Europe (SMD = -1.063, 95 % CI = [-1.571, -0.556], p < 0.001) and Asia (SMD = -3.254, 95 % CI = [-4.687, -1.821], p < 0.001) but not in USA (SMD = -0.322, 95 % CI = [-0.657, 0.012], p = 0.059). The serum Se levels were lower in RA than healthy controls measured by graphite furnace atom absorption spectrometry (GFAAS) (SMD = -1.026, 95 % CI = [-1.522, -0.530], p < 0.001), electrothermal absorption spectrometry (EAS) (SMD = -1.197, 95 % CI = [-2.373, -0.020], p < 0.05), flame atomic absorption spectrophotometry (FAAS) (SMD = -0.681, 95 % CI = [-1.049, -0.313], p < 0.001), and inductively coupled plasma-mass spectrophotometer (ICP-MS) (SMD = -11.707, 95 % CI = [-15.189, -8.224], p < 0.001) but not by neutron activation analysis (NAA) (SMD = -0.674, 95 % CI = [-1.350, 0.003], p = 0.051). In conclusion, this meta-analysis supports a significant association between low serum Se concentration with RA. However, this finding needs further confirmation by a trans-regional multicenter study to obtain better understanding of causal relationship between serum Se with RA of different human races or regions.
26879360 How to Motivate Patients with Rheumatoid Arthritis to Quit Smoking. 2016 Apr OBJECTIVE: Seropositive rheumatoid arthritis (RA) is strongly linked to cigarette smoking, and smoking cessation is an essential step in RA management. Our objectives were to develop RA and smoking awareness materials and to evaluate the influence of the materials on awareness about the links between RA and smoking and on motivation to quit smoking. METHODS: A group of patients with seropositive RA in Fife, Scotland, were telephoned before the campaign, and the results of the precampaign questionnaire were used to develop the image for the campaign. After the campaign a second group of patients were questioned to ascertain the effect of the campaign. RESULTS: The 320 patient responses to the precampaign questionnaire revealed that many ex-smokers with RA had quit when they developed a known smoking-related disease such as emphysema. This concept was used to develop an image illustrating that RA is a smoking-related disease. The campaign was launched in Fife in 2011. The postcampaign questionnaire involving 380 patients revealed that there was 21% higher awareness of a link between RA and smoking and 45% higher awareness that smoking could interfere with treatment of RA. In total, 13/75 smokers who had cut down since the campaign had been influenced by the new information. CONCLUSION: The new materials have successfully increased patients' knowledge of the link between RA and smoking and the effect of smoking on RA therapy. RA smokers' attitudes to smoking may have been affected by the campaign.
24467668 (99) Tc-methylene diphosphonate improves rheumatoid arthritis disease activity by increasi 2016 Jun AIM: γδ T cells exhibit important functions in the pathogenesis of rheumatoid arthritis (RA). In recent years, numerous studies harnessed the γδ T cell-activating capacity of aminobiphosphonates for the treatment of malignant tumors. As (99) Tc-methylene diphosphonate ((99) Tc-MDP) has long been widely used for the treatment of RA in China with good efficacy, we are interested in whether this drug exerts its therapeutic effect on RA by modulating peripheral γδ T cells of RA patients. OBJECTIVES: To investigate the effect of (99) Tc-MDP on the frequency of γδ T cells and CD4(+) CD25(+) Foxp3(+) Tregs in the peripheral blood of patients with active RA. METHODS: Nineteen patients with active RA were treated with (99) Tc-MDP intravenously at a dose of 20 μg/day consecutively for 10-14 days. Before and after treatment, the main clinical and laboratory parameters for each patient were evaluated. The frequency of CD3(+) γδ(+) T cells and CD4(+) CD25(+) Foxp3(+) Tregs was detected by flow cytometry. Serum levels of interferon (IFN)-γ, tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-10 and transforming growth factor (TGF)-β were measured with enzyme-linked immunosorbent assay. RESULTS: After intravenous (99) Tc-MDP therapy, the frequency of peripheral CD3(+) γδ(+) T cells and CD4(+) CD25(+) Foxp3(+) Tregs were significantly elevated, paralleled with decreased serum levels of TNF-α and IL-6 and increased level of serum TGF-β. The elevation of peripheral CD3(+) γδ(+) T cells was positively correlated with increased serum TGF-β and decreased disease activity. CONCLUSION: (99) Tc-MDP may improve the activity of RA through upregulating the frequency of peripheral γδ T cells and CD4(+) CD25(+) Foxp3(+) Tregs as well as affecting the serum cytokine environment by increasing TGF-β and decreasing TNF-α and IL-6.
27915033 Survivin controls biogenesis of microRNA in smokers: A link to pathogenesis of rheumatoid 2017 Mar MicroRNAs (miRs) represent a part of epigenetic control of autoimmunity gaining increasing attention in rheumatoid arthritis (RA). Since cigarette smoking plays important role in RA pathogenesis and reprograms transcriptional profile of miRNAs, we ask if the onco-protein survivin, a novel biomarker of RA, may provide a link between smoking and miRNA. Studying survivin expression in leukocytes of 144 female RA patients we observed that smoking patients had higher survivin transcription and a remarkable spreading of survivin isoforms. This was associated with restricted pattern and low production of miRs. Additionally, miRNA processing enzymes Dicer and DGRC8 were decreased in the patients with survivin isoform spreading. The direct contribution of survivin in miRs biogenesis was confirmed by a massive increase of miRs production following inhibition of survivin in leukocyte cultures. Dicer is shown to mediate these effects of survivin. Chromatin immunoprecipitation analysis demonstrated binding of survivin to the Dicer promoter region. Dicer expression increased 5-folds following survivin inhibition. Taken together, this study presents experimental evidence of a novel cellular function of survivin, control of miRs biogenesis. Up-regulation of survivin in smokers suggests its role as effector of the adverse epigenetic control in RA.
27268027 Vaccination with endosomal unknown epitopes produces therapeutic response in rheumatoid ar 2016 Jun 7 BACKGROUND: Our previous results showed that intrasynovial Rifamycin SV caused the lysis of synoviocites and freed the autoantigens which in turn stimulated the immunoregulatory rather than autoreactive T cell response in rheumatoid patients. Here, we hypothesize that disruption in vitro of peripheral blood mononuclear cells, by freeze/thawing or by lytic action of Rifamycin SV, would induce the release of endosomal pathogenic autoantigens from APCs present in the circulation, which could then be isolated from degrading enzymes by ultrafiltration. METHODS: The preparation of the ultrafiltrates are based on the rupture of PBMCs (5 × 10(6) cells/mL) by the addition of Rifamycin SV in culture (250 μg/mL), which causes the lysis of 90 % of the cells in 3 h, or by three cycles of freeze/thawing of the PBMC, from -80 °C to room temperature. The lysate and the fragmented cells were then centrifuged and ultrafiltered by passage through a filtration device with a cut-off of 10 kDa. Also the synovial fluid was subjected to ultrafiltration. RESULTS AND CONCLUSIONS: At clinical monitoring of the 30th day, 22/58 (38 %) patients subcutaneously treated with the autologous ultrafiltrate prepared by the freeze/thawing of PBMCs reached an ACR20. Comparable results were obtained with the other two ultrafiltrates. Cell cultures The addition of ultrafiltrates to rheumatoid PBMCs cultures led to the upregulation of a marker for T-regulatory cells, and downregulation of a cell proliferation marker; changes that together have the meaning of a global immunomodulatory response and that only a specific antigen (ultrafiltrate UF-f/t) might induce in the rheumatoid patient, probably by activating pre-existing protective network. Experimental arthritis All the ultrafiltrates except that prepared by Rifamycin SV were able to modulate the adjuvant arthritis in rats. In particular, longlasting synovial fluid induced a significant reduction of the severity of subsequent arthritis (p < 0.01) while SF from recent RA effusion (5-10 days after a previous complete extraction) and knee osteoarthrosis were ineffective. It is reasonable to assume there are at least two unknown endosomal immunoactive epitopes; one developing its immunotherapeutic property in RA, and the other, related to the molecule of HSP60, reduces the severity of oncoming arthritis. Both epitopes are present in humans, have a molecular weight of ≤10 kDa and do not appear to be bystander antigens. Please see Additional file 1 for the abstract in Italian.
26945334 The role of anticitrullinated protein antibodies in the early stages of rheumatoid arthrit 2016 May PURPOSE OF REVIEW: This review provides an update on the recent discoveries on the role of anticitrullinated protein antibodies (ACPA) in early rheumatoid arthritis (RA). RECENT FINDINGS: RA is characterized by an immune response against posttranslationally modified proteins, in particular citrullinated proteins. Recent studies have found that the ACPA response matures shortly before clinical disease manifests itself and is characterized by an increase in titre, isotype switching, antigen-recognition profile, and a change in the Fc-glycosylation pattern. To date, many citrullinated autoantigens have been identified and novel studies suggest that the human leucocyte antigen class II locus may directly influence the maturation of the ACPA response via antigen-specific T cells. Clinical studies have demonstrated that effective treatment of arthritis can lead to reduced ACPA levels or a change in composition of ACPA. In addition to ACPA, autoantibodies targeting other posttranslational modifications have been identified and may be associated with disease prognosis. SUMMARY: Key studies have demonstrated that autoimmunity against citrullinated proteins is already present in preclinical RA and matures over time. Future studies are required to reveal whether autoantibodies and the B cells that produce them play a role in disease development or can function as biomarkers for disease maturation.
26543364 Methotrexate-loaded lipid-core nanocapsules are highly effective in the control of inflamm 2015 BACKGROUND: Rheumatoid arthritis (RA) is the most common autoimmune disease in the word, affecting 1% of the population. Long-term prognosis in RA was greatly improved following the introduction of highly effective medications such as methotrexate (MTX). Despite the importance of this drug in RA, 8%-16% of patients must discontinue the treatment because of adverse effects. Last decade, we developed a promising new nanocarrier as a drug-delivery system, lipid-core nanocapsules. OBJECTIVE: The aim of the investigation reported here was to evaluate if methotrexate-loaded lipid-core nanocapsules (MTX-LNC) reduce proinflammatory and T-cell-derived cytokines in activated mononuclear cells derived from RA patients and even in functional MTX-resistant conditions. We also aimed to find out if MTX-LNC would reduce inflammation in experimentally inflammatory arthritis at lower doses than MTX solution. METHODS: Formulations were prepared by self-assembling methodology. The adjuvant arthritis was induced in Lewis rats (AIA) and the effect on edema formation, TNF-α levels, and interleukin-1 beta levels after treatment was evaluated. Mononuclear cells obtained from the synovial fluid of RA patients during articular infiltration procedures were treated with MTX solution and MTX-LNC. For in vitro experiments, the same dose of MTX was used in comparing MTX and MTX-LNC, while the dose of MTX in the MTX-LNC was 75% lower than the drug in solution in in vivo experiments. RESULTS: Formulations presented nanometric and unimodal size distribution profiles, with D[4.3] of 175±17 nm and span of 1.6±0.2. Experimental results showed that MTX-LNC had the same effect as MTX on arthritis inhibition on day 28 of the experiment (P<0.0001); however, this effect was achieved earlier, on day 21 (P<0.0001), by MTX-LNC, and this formulation had reduced both TNF-α (P=0.001) and IL-1α (P=0.0002) serum levels by the last day of the experiment. Further, the MTX-LNC were more effective at reducing the cytokine production from mononuclear synovial cells than MTX. CONCLUSION: The MTX-LNC were better than the MTX solution at reducing proinflammatory cytokines and T-cell-derived cytokines such as interferon-gamma and interleukin-17A. This result, combined with the reduction in the dose required for therapy, shows that MTX-LNC are a very promising system for the treatment of RA.
27129711 Delayed wound healing and postoperative surgical site infections in patients with rheumato 2016 Jun Biological disease-modifying antirheumatic drugs (bDMARDs) have become more popular for treating rheumatoid arthritis (RA). Whether or not bDMARDs increase the postoperative risk of surgical site infection (SSI) has remained controversial. We aimed to clarify the effects of bDMARDs on the outcomes of elective orthopedic surgery. We used multivariate logistic regression analysis to analyze risk factors for SSI and delayed wound healing among 227 patients with RA (mean age, 65.0 years; disease duration, 16.9 years) after 332 elective orthopedic surgeries. We also attempted to evaluate the effects of individual medications on infection. Rates of bDMARD and conventional synthetic DMARD (csDMARD) administration were 30.4 and 91.0 %, respectively. Risk factors for SSI were advanced age (odds ratio [OR], 1.11; P = 0.045), prolonged surgery (OR, 1.02; P = 0.03), and preoperative white blood cell count >10,000/μL (OR, 3.66; P = 0.003). Those for delayed wound healing were advanced age (OR, 1.16; P = 0.001), prolonged surgery (OR, 1.02; P = 0.007), preoperative white blood cell count >10,000/μL (OR, 4.56; P = 0.02), and foot surgery (OR, 6.60; P = 0.001). Risk factors for SSI and medications did not significantly differ. No DMARDs were risk factors for any outcome examined. Biological DMARDs were not risk factors for postoperative SSI. Foot surgery was a risk factor for delayed wound healing.
26214269 Effective Treatment for Rapid Improvement of Both Disease Activity and Self-Reported Physi 2016 Feb OBJECTIVE: To investigate the longitudinal relationship between disease activity and self-reported physical activity (PA) in patients with early rheumatoid arthritis during the first year of treatment with combination therapy. METHODS: PA was measured with the Short Questionnaire to Assess Health-Enhancing Physical Activity at baseline, 13 weeks, 26 weeks, and 52 weeks after start of treatment in the context of the Combinatietherapie Bij Reumatoïde Artritis-Light trial. The reported PA classified patients as meeting or not meeting the World Health Organization (WHO) PA guideline (cutoff: 150 minutes of moderate-to-intense activity per week). Other measurements included the Disease Activity Score (DAS). Since both treatment arms showed equal treatment effect, these were analyzed as 1 group with simple before-after analyses and generalized estimating equations (GEE). RESULTS: In these analyses, 140 patients (86% of the trial population, 66% women, mean age 52 years) with complete data were included. At entry, 69% of the patients met the WHO PA guideline, increasing to 90% at week 13, and remaining stable at 89% after 1 year (P < 0.001). Mean DAS improved from 4.0 to 1.8 during the first year of treatment (P < 0.001). In GEE analyses, DAS decreases were significantly associated with PA increases (P = 0.008). Patients with clinically relevant responses (expressed as DAS remission, European League Against Rheumatism good response or American College of Rheumatology criteria for 70% improvement response) showed higher PA levels compared to nonresponders, regardless of the definition of response, for both the WHO and Dutch PA guideline. CONCLUSION: Early rheumatoid arthritis patients using combination therapy improved both disease activity and PA, a beneficial effect persisting for at least 1 year.
26151734 Effect of Sesamin Supplementation on Cardiovascular Risk Factors in Women with Rheumatoid 2016 May OBJECTIVE: Rheumatoid arthritis (RA) is an inflammatory disease with increased mortality from cardiovascular disease (CVD). Oxidative stress has a critical role in the pathogenesis of RA and CVD. Sesamin, the main lignin constituent of sesame, has several antioxidant and anti-inflammatory effects. This study aimed to investigate the effects of sesamin supplementation on anthropometric indices, lipid profile, blood pressure, and oxidative stress markers in women with RA. METHODS: In this randomized, double-blind, placebo-controlled clinical trial, 44 patients with RA were randomly divided into 2 groups (intervention and control). Patients consumed 200 mg/day sesamin supplement and placebo in the intervention and control groups, respectively, for 6 weeks (spring 2014). At baseline and at the end of the study, anthropometric indices and blood pressure were assessed. Serum concentrations of lipid profile, malondialdehyde (MDA), and total antioxidant capacity (TAC) were also determined. RESULTS: At the end of study, sesamin supplementation significantly decreased serum levels of MDA (p = 0.018) and increased TAC and high-density lipoprotein cholesterol (HDL-C) levels in patients with RA (p = 0.020 and p = 0.007, respectively). In the sesamin group, the mean of weight, body mass index, waist-to-hip ratio, body fat, systolic blood pressure, and the concentration of other lipid profiles (triglycerides, total cholesterol, and low-density lipoprotein cholesterol [LDL-C]) were also significantly decreased at the end of study compared to baseline values (p < 0.05). However, the difference between the 2 groups was not statistically significant in this regard (p > 0.05). CONCLUSION: Sesamin exhibited a protective effect on cardiovascular risk factors in patients with RA. However, further investigation is suggested.
25274633 Choline kinase inhibition in rheumatoid arthritis. 2015 Jul OBJECTIVES: Little is known about targeting the metabolome in non-cancer conditions. Choline kinase (ChoKα), an essential enzyme for phosphatidylcholine biosynthesis, is required for cell proliferation and has been implicated in cancer invasiveness. Aggressive behaviour of fibroblast-like synoviocytes (FLS) in rheumatoid arthritis (RA) led us to evaluate whether this metabolic pathway could play a role in RA FLS function and joint damage. METHODS: Choline metabolic profile of FLS cells was determined by (1)H magnetic resonance spectroscopy ((1)HMRS) under conditions of ChoKα inhibition. FLS function was evaluated using the ChoKα inhibitor MN58b (IC₅₀=4.2 μM). For arthritis experiments, mice were injected with K/BxN sera. MN58b (3 mg/kg) was injected daily intraperitoneal beginning on day 0 or day 4 after serum administration. RESULTS: The enzyme is expressed in synovial tissue and in cultured RA FLS. Tumour necrosis factor (TNF) and platelet-derived growth factor (PDGF) stimulation increased ChoKα expression and levels of phosphocholine in FLS measured by Western Blot (WB) and metabolomic studies of choline-containing compounds in cultured RA FLS extracts respectively, suggesting activation of this pathway in RA synovial environment. A ChoKα inhibitor also suppressed the behaviour of cultured FLS, including cell migration and resistance to apoptosis, which might contribute to cartilage destruction in RA. In a passive K/BxN arthritis model, pharmacologic ChoKα inhibition significantly decreased arthritis in pretreatment protocols as well as in established disease. CONCLUSIONS: These data suggest that ChoKα inhibition could be an effective strategy in inflammatory arthritis. It also suggests that targeting the metabolome can be a new treatment strategy in non-cancer conditions.
26983453 A genome-wide association study identifies SLC8A3 as a susceptibility locus for ACPA-posit 2016 Jun OBJECTIVE: RA patients with serum ACPA have a strong and specific genetic background. The objective of the study was to identify new susceptibility genes for ACPA-positive RA using a genome-wide association approach. METHODS: A total of 924 ACPA-positive RA patients with joint damage in hands and/or feet, and 1524 healthy controls were genotyped in 582 591 single-nucleotide polymorphisms (SNPs) in the discovery phase. In the validation phase, the most significant SNPs in the genome-wide association study representing new candidate loci for RA were tested in an independent cohort of 863 ACPA-positive patients with joint damage and 1152 healthy controls. All individuals from the discovery and validation cohorts were Caucasian and of Southern European ancestry. RESULTS: In the discovery phase, 60 loci not previously associated with RA risk showed evidence for association at P < 5×10(-4) and were tested for replication in the validation cohort. A total of 12 loci were replicated at the nominal level (P < 0.05, same direction of effect as in the discovery phase). When combining the discovery and validation cohorts, an intronic SNP in the Solute Carrier family 8 gene (SLC8A3) was found to be associated with ACPA-positive RA at a genome-wide level of significance RA [odds ratio (95% CI): 1.42 (1.25, 1.6), Pcombined = 3.19×10(-8)]. CONCLUSIONS: SLC8A3 was identified as a new risk locus for ACPA-positive RA. This study demonstrates the advantage of analysing relevant subsets of RA patients to identify new genetic risk variants.
27239922 [N-terminal pro-brain natriuretic peptide levels and diastolic dysfunction in patients wit 2016 AIM: To determine N-terminal pro-brain natriuretic peptide (NT-proBNP) levels in patients with early rheumatoid arthritis (RA) before the use of disease-modifying antirheumatic drugs (DMARDs); to compare NT-proBNP values with traditional risk factors (TRF), cardiovascular diseases (CVD), inflammatory markers, and left ventricular (LV) diastolic dysfunction (DD). SUBJECTS AND METHODS: The investigation enrolled 74 patients with a valid RA diagnosis (the 2010 ACR/EULAR criteria), 56 (74%) women, median (Me) age, 54 years; disease duration, 7 months; seropositive for IgM rheumatoid factor (87%) and/or anti-cyclic citrullinated peptide antibodies (100%) with no history of the use of DMARDs and glucocorticosteroids. Duplex scanning and echographic findings were used to assess TRF for CVD and carotid artery atherosclerosis (CAA) in all the patients with early RA prior to therapy. An E/A ratio was used as a criterion for LVDD. RESULTS: NT-proBNP concentrations in patients with early RA proved to be higher than those in the control group (p<0.0001). Higher-than-normal NT-proBNP levels were seen in 36 (49%) patients. The patients with early RA and elevated NT-proBNP values were older and had a higher body mass index (BMI) than those with normal NT-proBNP levels. Those with elevated NT-proBNP concentrations were more frequently found to have CAA, coronary calcification, and coronary heart disease; their intima-media thickness was also larger and C-reactive protein (CRP) levels higher than in those with normal NT-proBNP values. There were correlations between NT-proBNP levels and erythrocyte sedimentation rate, CRP, simplified disease activity index, and clinical disease activity index. Multivariate analysis revealed that chronic heart failure (CHF), CAA, CRP and low-density lipoprotein (LDL) levels, and BMI correlated with NT-proBNP concentrations. LVDD was detected in 35 (48%) patients with early RA. The level of NT-proBNP in patients with DD was higher than in those without DD. Higher-than-normal NT-proBNP values were observed in 23 (65%) and 12 (32%) patients with and without LVDD, respectively. The optimal NT-proBNP level for CHF detection was equal to 237.4 pg/ml (86% sensitivity and 85% specificity); the area under the ROC curve was 0.879. CONCLUSION: Just at the early disease stage, the patients are noted to have a high NT-proBNP level that is influenced by higher BMI, low LDL levels, CAA, CHF, and high CRP values. In the patients with early RA, the diagnostically significant NT-proBNP concentration for CHF detection was higher (237 pg/ml) than in those without RA (125 pg/ml). The patients with early RA should undergo NT-proBNP determination, LVDD screening, correction of TRF for CVD, atherosclerosis treatment, and remission achievement.
26970958 A Retrospective Cohort Study Comparing Utilization and Costs of Biologic Therapies and JAK 2016 Apr INTRODUCTION: Biologic therapies are used to treat several inflammatory diseases, including rheumatoid arthritis (RA), psoriasis (PsO), psoriatic arthritis (PsA), and ankylosing spondylitis (AS). Data from a commercial claims database were used to evaluate utilization and cost of biologic treatment for these conditions. METHODS: Data were obtained from the Optum Research Database. Patients were aged 18-63 years with diagnosis of moderate to severe RA, PsO, PsA, and/or AS and first (index) claim for biologics abatacept, adalimumab, certolizumab pegol, etanercept, golimumab, infliximab, rituximab, tocilizumab, or ustekinumab or non-biologic tofacitinib between March 1, 2011 and February 28, 2013. One-year treatment costs were based on observed paid amounts and used to impute dosing. Treatment patterns (persistence, switching, discontinuing, restarting) were evaluated. RESULTS: Data from 20,159 patients were analyzed for index medications abatacept (n = 583), adalimumab (n = 6521), certolizumab pegol (n = 415), etanercept (n = 9116), golimumab (n = 231), infliximab (n = 1906), rituximab (n = 295), tocilizumab (n = 165), ustekinumab (n = 922), and tofacitinib (n = 5). For patients with RA only, costs were lowest for tofacitinib ($18,769), rituximab ($19,569), or abatacept ($21,877), and ranged from $23,682 to $30,269 for all other medications. For patients with PsO only, costs were lowest for adalimumab ($29,186), etanercept ($31,212), and infliximab ($32,409) compared with ustekinumab ($53,746). For patients with PsA only, costs were lowest for etanercept ($26,916), followed by golimumab ($27,987), adalimumab ($28,749), and infliximab ($31,974). Costs were lowest with etanercept for RA plus PsA ($25,477) and for PsO plus PsA ($29,376), and with golimumab for AS only ($24,225). Across indications, annual costs were $29,521, $27,488, and $28,672 for adalimumab, etanercept, and infliximab, respectively; persistence was greatest with infliximab (range 66-79%) compared with 11-59% for all other biologics. CONCLUSION: One-year treatment costs varied considerably between medications and indications. Some newly approved agents had lower costs but further research is needed to confirm these estimates as more patients are treated. FUNDING: Immunex (a wholly owned subsidiary of Amgen Inc.) and Wyeth (acquired by Pfizer).
27086843 Pain in rheumatoid arthritis: models and mechanisms. 2016 Pain is one of the most challenging symptoms for patients with rheumatoid arthritis (RA). RA-related pain is frequently considered to be solely a consequence of inflammation in the joints; however, recent studies show that multiple mechanisms are involved. Indeed, RA pain may start even before the disease manifests, and frequently does not correlate with the degree of inflammation or pharmacological management. In this aspect, animal studies have the potential to provide new insights into the pathology that initiate and maintain pain in RA. The focus of this review is to describe the most commonly used animal models for studies of RA pathology, which have also been utilized in pain research, and to summarize findings providing potential clues to the mechanisms involved in the regulation of RA-induced pain.
27577564 A case of multiple hepatic lesions associated with methotrexate-associated lymphoprolifera 2016 Oct Patients receiving methotrexate (MTX) for the treatment of autoimmune disease are at a high risk of developing lymphoproliferative disorders (LPD), the so-called methotrexate-associated lymphoproliferative disorders (MTX-LPD). We recently performed abdominal ultrasonography (US) in a patient with rheumatoid arthritis (RA) who had developed hepatic dysfunction during the course of MTX therapy; the examination revealed multiple well-demarcated hepatic tumors with slightly irregular borders, the largest one measuring 9 cm in diameter. In view of the finding of portal and hepatic veins perforating the tumor, we suspected a diagnosis of malignant lymphoma and performed a hepatic tumor biopsy. Histopathological examination of the biopsy specimens revealed a diagnosis of diffuse large B-cell lymphoma, and we made a final diagnosis of MTX-LPD. MTX treatment was discontinued, which resulted in rapid resolution of the lesions. Resolution of MTX-LPD can be obtained just by discontinuation of MTX treatment. In patients receiving MTX therapy who are found to have hepatic tumors perforated by the portal vein and/or hepatic vein on abdominal US, it is advisable to perform hepatic tumor biopsy to facilitate differential diagnosis of MTX-LPD and enable a definite diagnosis.
27098382 Reactivation of occult hepatitis B virus infection under treatment with abatacept: a case 2016 Apr 21 BACKGROUND: Abatacept (ABA) is a fusion receptor protein containing the CTLA-4 domain that prevents the activation of naïve T cells by binding the CD80 and CD86 molecules expressed on the surface of dendritic cells, indicated for the treatment of moderate to severe rheumatoid arthritis (RA). There is still little evidence concerning the safety of ABA in RA patients with positive serology for hepatitis virus B (HBV) infection. CASE PRESENTATION: We report the case of a HBV infection reactivation in an ABA-treated male RA patient. The patient (caucasian race, 66-year-old) was diagnosed with RA in Novembre 2010 and in December 2010 he started a treatment with prednisone plus subcutaneous methotrexate. In October 2011, an anti-TNF agent (golimumab) was added but soon discontinued due to an adverse event. At baseline, screening for HBV markers showed a positivity for HBcAb and HBeAb IgG, being HBsAg, HBsAb, HBcAb IgM, HBeAg and HBV DNA negative. Serum amino-transferase (AST and ALT) levels were within the normal range. In January 2012 he was swapped to intravenous treatment with ABA 750 mg/month, that allowed the achievement of a good clinical response and the permanent discontinuation of corticosteroids. In November 2013, laboratory reports showed that he was positive for HBcAb but negative for the remaining HBV markers, and had a slightly increased AST level and, in December 2013, he became HBV DNA positive (326 IU/mL). In January 2014, his HBV DNA levels had further increased and ABA was stopped while maintaining MTX. He started lamivudine 100 mg/day in January 2014. After 1 month of lamivudine, his HBV DNA levels became undetectable (<10 IU/mL) and liver function was normal although RA had been reactivated (DAS28 5.53). Treatment with ABA was therefore resumed with the achievement of a good response after 6 months. The patient is currently being treated with lamivudine 100 mg/day, i.v. ABA 750 mg/month, and MTX 15 mg/week, with a good response (DAS28 2.27 in October 2015), and constantly monitored without any further evidence of HBV infection reactivation. CONCLUSIONS: Although there are still few reports in literature, we suggest caution in HBV- occult carriers RA patients undergoing a treatment with abatacept.