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ID PMID Title PublicationDate abstract
24681241 Preventing intense false positive and negative reactions attributed to the principle of EL 2014 May To study the possible involvement of potential environmental pathogens in the pathogenesis of autoimmune diseases, it is essential to investigate antibody responses to a variety of environmental agents and autologous components. However, none of the conventional ELISA buffers can prevent the false positive and negative reactions attributed to its principal, which utilizes the high binding affinity of proteins to plastic surfaces. The aims of this study are to reveal all types of non-specific reactions associated with conventional buffer systems, and to re-investigate antibody responses to potential environmental pathogenic and autologous antigens in patients with autoimmune diseases using a newly developed buffer system "ChonBlockâ„¢" by ELISA. Compared to conventional buffers, the new buffer was highly effective in reducing the most intense false positive reaction caused by hydrophobic binding of immunoglobulin in sample specimens to plastic surfaces, "background (BG) noise reaction", and other non-specific reactions without interfering with antigen-antibody reactions. Applying this buffer, we found that IgG antibody responses to Escherichia coli O111:B4, E. coli lipopolysaccharide (LPS) and peptidoglycan polysaccharide (PG-PS) were significantly lower or tended to be lower in patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE), whereas IgA antibody responses to these antigens were equal or tended to be higher compared to normal controls. As a consequence, the IgA/IgG antibody ratios against these agents were significantly higher in patients with RA and SLE, except for Crohn's disease, which showed significantly higher IgG responses to these antigens. To assay antibodies in human sera, it is indispensable to eliminate false positive and negative reactions by using an appropriate buffer system, and to include antigen non-coated blank wells to determine BG noise reactions of invidual samples. Finally, based on our preliminary analysis in this study, we propose that low IgG antibody responses to potential pathogenic environmental factors may be the fundamental disorder in autoimmune diseases.
24097136 Prolonged QTc interval predicts all-cause mortality in patients with rheumatoid arthritis: 2014 Jan OBJECTIVE: RA associates with an increased rate of sudden cardiac death (SCD). A prolonged QTc interval has been associated with arrhythmogenic and SCD in patients with long QT syndrome. Despite the previously reported contemporary association of CRP with SCD, thus far no studies have examined the association of QTc with mortality in RA, a condition characterized by high inflammatory burden. The aim of this study was to examine the role of electrocardiography (QT corrected interval) in predicting all-cause mortality in patients with RA who have an increased rate of SCD and a high inflammatory burden. METHODS: Three hundred and fifty-seven RA patients with detailed baseline clinical characterization and 12-lead ECGs were followed up for a mean of 73.0 (S.D. 18.3) months. Linear and Cox regression analyses were used to identify variables that associate with QTc and examine its association with all-cause mortality. RESULTS: The patients' mean age was 60.6 (S.D. 12.0) years, 267 (74.8%) were females and 54 (15.1%) died during the follow-up period. Age (β = 0.231, P < 0.001), gender (β = 0.137, P = 0.008) and CRP (β = 0.144, P = 0.006) associated independently with QTc in RA patients. The crude hazard ratio (HR) for total mortality per 50-ms increase in QTc was 2.17 (95% CI 1.21, 3.90). This association remained significant [HR = 2.18 (95% CI 1.09, 4.35)] after adjustment for identified confounders (cardiovascular and RA specific), but was lost [HR = 1.73 (95% CI 0.83, 3.62)] when CRP was included in the model. CONCLUSION: A 50-ms increase in QTc interval associates with a doubling of the hazard for all-cause mortality in patients with RA. The observed contemporary association of QTc with CRP levels indicates a potentially hazardous interplay between inflammation and arrhythmogenesis. Future studies are needed to confirm the above findings and explore underlying mechanisms.
25261692 Aberrant CD200/CD200R1 expression and its potential role in Th17 cell differentiation, che 2015 Apr OBJECTIVE: CD200/CD200R1 signalling has an immunoregulatory effect on the activation threshold of the inflammatory immune response and maintains immune homeostasis. In this study we evaluated the status of CD200/CD200R1 interaction in patients with RA. METHODS: The expression of CD200 and CD200R1 was examined by immunohistochemistry and flow cytometry and was compared between RA patients and healthy controls (HCs). Sorted CD4(+) T cells were stained with carboxyfluorescein succinimidyl ester (CFSE) and annexin V-propidium iodide to evaluate the effect of CD200 on cell proliferation and apoptosis. The effect of CD200 on Th17 differentiation, function and osteoclastogenesis was determined by flow cytometry, transwell migration assay and immunocytochemistry, respectively. RESULTS: The proportion of CD200(+) cells and CD200R1(+) cells in peripheral blood mononuclear cells, peripheral CD14(+) cells and CD4(+) T cells was significantly lower in the RA patients than in HCs, whereas the number of CD200(+) cells was higher in synovium from RA patients than in that from HCs. After treatment with infliximab and MTX we found increased expression of peripheral CD200/CD200R1 that correlated with a decrease in the 28-joint DAS. CD200Fc in vitro partially inhibited CD4(+) T cell proliferation, promoted CD4(+) T cell apoptosis, reduced CD4(+) T cell differentiation into Th17 cells and down-regulated CCR6-mediated Th17 chemotaxis in cells from RA patients. In addition, the engagement of the CD200 receptors on CD14(+) cells with CD200Fc in vitro reduced osteoclastogenesis and inhibited CD14(+) cell-driven Th17 differentiation. CONCLUSION: Abnormal CD200/CD200R1 expression in RA may contribute to abnormal Th17 cell differentiation, chemotaxis and osteoclastogenesis.
23311682 Predictors of asymmetric dimethylarginine levels in patients with rheumatoid arthritis: th 2013 OBJECTIVE: To determine whether demographic, inflammatory, and metabolic factors predict elevated asymmetric dimethylarginine (ADMA) levels in rheumatoid arthritis (RA). METHOD: A total of 67 RA patients [mean age 56 ± 12 years, median disease duration 8 (3-15) years] were assessed. Routine biochemistry tests, lipid profile, glycaemic profile [glucose, insulin, homeostasis model assessment (HOMA), quantitative insulin sensitivity check index (QUICKI)], and inflammatory markers were measured in all patients. ADMA levels were measured by enzyme-linked immunosorbent assay (ELISA). Regression analyses were performed to identify predictors of ADMA in RA. RESULTS: Regression analysis revealed that HOMA (β = 0.149, p = 0.003) was an independent predictor of ADMA in RA. From the drug factors, anti-hypertensive medication use was associated with lower ADMA levels (β = -0.081, p = 0.004). ADMA was not associated with RA disease-related parameters or any of the other cardiovascular risk factors that were assessed. CONCLUSIONS: HOMA, a strong indicator of insulin resistance, seems to be the main predictor of elevated ADMA levels in RA patients; ADMA may reflect an important pathway linking abnormal insulin metabolism with endothelial dysfunction in RA.
24055018 Plasma level of neopterin as a marker of disease activity in treated rheumatoid arthritis 2013 Nov Immune system activation is known to be involved in the progression of rheumatoid arthritis (RA). The pro-inflammatory cytokine interferon-γ in various cells, including monocytes, induces neopterin production. Plasma level of neopterin has been measured in many autoimmune diseases and can be used as a marker of cellular immunity activation. In this study we measured the plasma level of neopterin in 418 treated RA patients and 398 age and sex matched healthy people by high pressure liquid chromatography (HPLC) method. Disease activity score was calculated in all patients by DAS-CRP method. Plasma level of neopterin was compared between RA and control groups. We also determined the association between neopterin level with gender and disease activity score in RA patients. Significantly higher level of neopterin was observed in RA patients compared to healthy controls. Moreover, there was higher neopterin level in male RA patients versus female patients. Plasma neopterin level was increased in patients with active disease and also was correlated with disease activity parameters. There was a significant correlation of plasma level of neopterin with age in both RA and control group and also age of onset and disease duration in RA patients. Anti-CCP positive patients had higher level of neopterin in comparison to anti-CCP negative patients and there was a significant correlation between neopterin level and anti-CCP titer. Our results indicated that neopterin is a sensitive marker for assaying background inflammation and disease activity score in RA patients and may be used as a marker for evaluation of therapy efficacy.
23254357 Genetic variation in the serotonin receptor gene affects immune responses in rheumatoid ar 2013 Mar Many genetic variants associate with the risk of developing rheumatoid arthritis (RA); however, their functional roles are largely unknown. Here, we aimed to investigate whether the RA-associated serotonin receptor 2A (HTR2A) haplotype affects T-cell and monocyte functions. Patients with established RA (n=379) were genotyped for two single-nucleotide polymorphisms (SNPs) in the HTR2A locus, rs6314 and rs1328674, to define presence of the risk haplotype for each individual. Patients with and without the RA-associated TC haplotype were selected and T-cell and monocyte function was monitored following in vitro stimulations with staphylococcal enterotoxin B and lipopolysaccharide (LPS) using multiparameter flow cytometry. Within the cohort, 44 patients were heterozygous for the TC haplotype (11.6%) while none were homozygous. Upon stimulation, T cells from TC-carrier patients produced more proinflammatory cytokines (tumor necrosis factor alpha (TNF-α), interleukin-17 (IL-17) and interferon gamma (IFN-γ)) and monocytes produced higher levels of TNF-α compared with patients carrying the non-TC haplotype (P<0.05 and 0.01, respectively). Such cytokine production could be inhibited in the presence of the selective 5-HT2 receptor agonist (2,5-Dimethoxy-4-iodoamphetamine, DOI); interestingly, this effect was more pronounced in TC carriers. Our data demonstrate that association of RA with a distinct serotonin receptor haplotype has functional impact by affecting the immunological phenotype of T cells and monocytes.
25483574 Patient experiences with intensive combination-treatment strategies with glucocorticoids f 2015 Mar OBJECTIVES: To investigate patients' experiences with intensive combination-treatment strategies with glucocorticoids (ICTS-GCs) in the early phase of early rheumatoid arthritis (ERA) treatment. METHODS: We interviewed 26 participants individually, 4-6 months after initiation of ICTS-GCs (t1). Fourteen participants from the same sample took part in one of three focus groups at least 1 year after treatment initiation (t2). Each interview was audio-recorded, literally transcribed and thematically coded. RESULTS: The participants described concerns and feelings about ICTS-GCs that changed over time; for example, a fear of side effects diminished when the treatment effects were beneficial or expected side effects did not materialize. Moreover, participants indicated additional information needs at t1 and t2. The most used sources of information were healthcare professionals, relatives, and the Internet. Furthermore, participants reported on their relationship with healthcare professionals and the need for trust and reassurance, especially at t1. Lastly, participants described their personal self-management strategies. CONCLUSION: Despite their concerns at treatment initiation, most participants had positive experiences with ICTS-GCs. PRACTICE IMPLICATIONS: Healthcare professionals should be aware that, in the early phase of treatment, they can address patients' concerns, they are the most important information source, they need to create a relationship of trust, and guide patients in self-management strategies.
24204921 SMAD3 rs17228212 gene polymorphism is associated with reduced risk to cerebrovascular acci 2013 Rheumatoid arthritis (RA) is a complex polygenic inflammatory disease associated with accelerated atherosclerosis and increased risk of cardiovascular (CV) disease. Previous genome-wide association studies have described SMAD3 rs17228212 polymorphism as an important signal associated with CV events. The aim of the present study was to evaluate for the first time the relationship between this gene polymorphism and the susceptibility to CV manifestations and its potential association with the presence of subclinical atherosclerosis assessed by the evaluation of carotid intima-media thickness (cIMT) in patients with RA. METHODS: One thousand eight hundred and ninety-seven patients fulfilling classification criteria for RA were genotyped for SMAD3 rs17228212 gene polymorphism through TaqMan genotyping assay. Also, subclinical atherosclerosis determined by the assessment of cIMT was analyzed in a subgroup of these patients by carotid ultrasonography. RESULTS: No statistically significant differences were observed when allele frequencies of RA patients with or without CV events were compared. Nevertheless, when RA patients were stratified according to anti-cyclic citrullinated peptide (anti-CCP) status, we found that in RA patients who were negative for anti-CCP antibodies, the presence of C allele of SMAD3 rs17228212 polymorphism conferred a protective effect against the risk of cerebrovascular accident (CVA) after adjustment for demographic and classic CV risk factors (HR [95%CI]=0.36 [0.14-0.94], p=0.038) in a Cox regression model. Additionally, correlation between the presence of C allele of SMAD3 rs17228212 polymorphism and lower values of cIMT was found after adjustment for demographic and classic CV risk factors (p-value=0.0094) in the anti-CCP negative RA patients. CONCLUSIONS: Our results revealed that SMAD3 rs17228212 gene variant is associated with lower risk of CVA and less severe subclinical atherosclerosis in RA patients negative for anti-CCP antibodies. These findings may have importance to establish predictive models of CV disease in RA patients according to anti-CCP status.
24619653 Induction therapy with combination TNF inhibitor and methotrexate in early rheumatoid arth 2014 May With the introduction of more objective disease activity measures and the development of biological therapies, there were dramatic changes in the treatment of rheumatoid arthritis (RA). The combination therapy with tumor necrosis factor (TNF) inhibitor and methotrexate (MTX) has unprecedentedly improved prognosis and outcomes, and very low disease activity or remission has been achievable goal in RA. Although the concept of remission induction and maintenance was first discussed in longstanding RA patients, several clinical trials have demonstrated that there is a therapeutic window of opportunity, and early effective control of inflammation in early RA could lead to less joint damage and better long-term outcomes. Emerging evidence suggests that early combination therapy with TNF inhibitor and MTX leads to rapid clinical remission and thereby improved quality of life. Furthermore, remission status may be sustained in some patients even if a TNF inhibitor is discontinued after sustained remission in early RA patients. While there are many potential benefits of early remission induction therapy with the combination of a TNF inhibitor and MTX, the best therapeutic regimen and strategy for remission induction and maintenance in early RA remain controversial. There are no data to decide a priori when and in whom TNF blocker drugs are indicated in early disease-modifying anti-rheumatic drug (DMARD)-naïve RA.
23537991 Association between the polymorphisms of glutathione S-transferase genes and rheumatoid ar 2013 May 25 The glutathione S-transferases (GSTs) are a family of phase II xenobiotic metabolizing enzymes known to be involved in the detoxification and elimination of reactive oxygen species (ROS), thus defending tissues against oxidative stress. Recently, several studies have examined the potential contributions of GSTM1 and GSTT1 gene polymorphisms toward susceptibility to rheumatoid arthritis (RA), but these studies have produced diverse results. To verify the association between GSTM1 and GSTT1 gene polymorphisms and susceptibility to RA, we conducted a meta-analysis of all relevant reports cited in MEDLINE/PubMed before April 2012. A meta-analysis on the association between the GSTM1 polymorphism and RA was performed for 4636 patients with RA and 3916 controls from 8 published studies. In addition, a total of 5 studies involving 3174 RA patients and 2958 controls were considered in the meta-analysis of the association between the GSTT1 polymorphism and RA. No significant association was found between the GSTM1 null genotype and RA susceptibility in all subjects; however, a significant increased risk was found in East Asians. The GSTT1 null genotype was not associated with susceptibility to RA in any study subject. No apparent effect of smoking was found in stratified analysis. The results of our meta-analysis indicated that the GSTM1 null genotype is significantly associated with RA in East Asians alone, indicating that GSTM1 is another non-human leukocyte antigen (non-HLA) susceptibility gene for RA in East Asian populations.
24330219 Achieving consensus in ultrasonography synovitis scoring in rheumatoid arthritis. 2014 Sep OBJECTIVE: Ultrasonography is sensitive for synovitis detection but interobserver variation in both acquisition and image interpretation is still a concern. The objective was to assess if a short collegiate consensus would improve inter-observer reliability in scoring of synovitis. METHODS: Eight rheumatologists (Singapore) participated in a 1-day consensus meeting divided into: (i) still-image interpretation and consensus followed by; (ii) image acquisition and interpretation, according to definitions and synovitis scoring rules endorsed by Outcome Measures in Rheumatology (OMERACT) and TUI (Targeted Ultrasound Initiative). Interobserver reliability of semiquantitative scoring in B-mode, Power Doppler (PDUS) and European League Against Rheumatism (EULAR)-OMERACT PDUS composite score was assessed by intraclass correlation co-efficient (ICC). Agreement at the joint region level was calculated using prevalence-adjusted-biased-adjusted-kappa (PABAK). RESULTS: For B-mode still images, ICC was good at 0.75 (95% CI 0.66-0.82) while for PDUS images this was excellent at ICC = 0.88 (95% CI 0.83-0.92) with ICC improving by 12% for B-mode and 13% for PDUS respectively. During image acquisition and interpretation, B-mode scoring showed ICC = 0.75 (95% CI 0.66-0.84) while for PDUS the ICC was lower at 0.59 (95% CI 0.48-0.72). The ICC for OMERACT PDUS composite synovitis scoring was good at 0.77 (95% CI 0.68-0.85). At the joint level, agreement varied with PABAK being excellent in the small joints of the hands but poor to fair in the wrists, elbows, ankles and metatarsophalangeal joints, and no agreement at the knees (PABAK range -0.34 to 0.85). CONCLUSION: A consensus meeting was useful in improving interobserver variation in US synovitis scoring of still images, but image acquisition and interpretation especially in non-hand joints require further standardization.
25203494 Behavioral and clinical factors associated with self-reported abnormal Papanicolaou tests 2014 Sep BACKGROUND: Some evidence suggests that women with rheumatoid arthritis (RA) are at increased risk for the development of cervical cancer; however, it is unclear how this increase risk is conferred. We aimed to assess the factors related to abnormal Papanicolaou (Pap) tests in women with RA to determine whether they are similar to those reported for the general population. METHODS: A structured questionnaire was mailed to 503 female patients from a longitudinal RA cohort. The survey included items on sociodemographic, behavioral, and gynecological factors. Univariate and multivariable logistic regression models examined the association of self-reported abnormal Pap results with a number of potential behavioral risk factors. RESULTS: The questionnaire response rate was 57.5% (n=289). Median age was 61 years and 97% had ≥1 Pap test previously. Twenty-nine percent of respondents reported a previous abnormal Pap result. In the multivariable logistic model adjusted for age, number of lifetime sexual partners, age at menarche, birth control use, and history of sexually transmitted disease (STD), ever using birth control (odds ratio [OR] 2.31, 95% confidence interval [CI] 1.18-4.52) and previous STD (OR 3.38, 95% CI 1.70-6.70) were associated with an increased risk of abnormal Pap result. Compared with either the state or national population, a greater proportion of the respondents was older, married, and previous smokers, and completed postsecondary education and obtained a Pap test. CONCLUSIONS: In this cross-sectional study, self-reported abnormal Pap results were associated with use of birth control and history of STD in RA patients.
23660301 The extrapituitary prolactin promoter polymorphism is associated with rheumatoid arthritis 2013 Aug 1 Prolactin (PRL) is a hormone-cytokine that has been involved in autoimmunity due to its immunoregulatory and lymphoproliferative effects. It is produced by various extrapituitary sites including immune cells, under control of a superdistal promoter that contains a single nucleotide polymorphism -1149 G/T previously associated with rheumatoid arthritis (RA) susceptibility in European population. The aim of this study was to investigate the association of the extrapituitary PRL -1149 G/T promoter polymorphism with clinical parameters, clinical activity and disability indices in RA patients from Western Mexico and to analyze the PRL mRNA expression according to the PRL -1149 G/T promoter polymorphism in total leucocytes from RA patients and controls. We conducted a case-control study that included 258 RA patients and 333 control subjects (CS). The DNA samples were genotyped using the PCR-RFLP method and the PRL mRNA expression was determined by quantitative real time PCR. PRL serum levels and antibodies to cyclic citrullinated peptides (anti-CCP) were measured with ELISA. We found significant differences in the genotype (p=0.022) and allelic (p=0.046) distribution of the polymorphism between RA patients and control subjects. According to the dominant genetic model, there is an association between the T allele (GT+TT genotypes) and decreased RA susceptibility in comparison to the G allele carriers (GG genotype) (OR 0.64, 95% CI 0.45-0.92; p=0.011). The T allele carriers (GT+TT genotypes) had lower titers of anti-CCP antibodies in comparison to the G allele carriers (GG genotype) (median, 66 U/mL vs. 125 U/mL; p=0.03). Furthermore, the GG homozygotes had higher PRL mRNA expression in comparison to the GT heterozygotes, and this latter with respect to the TT homozygotes, in both groups (RA: 1>0.72>0.19; CS: 1>0.54>0.28). However, PRL serum levels were similar in both groups. Our results suggest that the PRL -1149 T allele is a genetic marker for decreased RA susceptibility and is associated with lower titers of anti-CCP antibodies in Mexican population. We also suggest influence of genotype upon PRL mRNA expression.
22552437 PADI4 polymorphisms and susceptibility to rheumatoid arthritis: a meta-analysis. 2013 Jan The objective of the study was to investigate the association between peptidylarginine deiminase 4 (PADI4) polymorphism and susceptibility to rheumatoid arthritis (RA). An electronic searching strategy was employed to collect relevant studies on the association between PADI4 polymorphism and susceptibility to RA. The odds ratio (OR) with the 95 % confidence interval (95 % CI) was used to evaluate the RA risk presented by PADI4 polymorphism. Fixed or random effects models were selected based on heterogeneity. Publication bias was assessed using funnel plots, Begg's test, and Egger's test. A total of 27 studies from 21 articles were included. Six gene loci (padi4_94, 104, 92, 90, 89, and 100) were chosen for the meta-analysis. The pooled ORs (95 % CI) for allele 2 versus 1 were 1.08 (1.05-1.12), 1.17 (1.12-1.23), 1.26 (1.18-1.36), 1.17 (1.10-1.24), 1.30 (1.17-1.44), and 1.25 (1.11-1.40), respectively. All six SNPs were significantly associated with RA in Asian populations. Three SNPs (PADI4_104, 90, 89) showed significant associations, while the other three SNPs (PADI4_94, 92, 100) exhibited no associations in the European population. A dose-response relationship between allele 2 of PADI4 and the risk of RA was also identified. In conclusion, this meta-analysis suggests that PADI4 polymorphisms represent a significant risk factor for RA, especially in Asians.
23591348 [Comparison of ACR/EULAR remission criterion of rheumatoid arthritis published in 2011 yea 2013 Apr 18 OBJECTIVE: To evaluate and compare the advantage and utility of the 2011 ACR/EULAR criterion and the other remission criteria of rheumatoid arthritis. METHODS: The questionnaires for RA patients were used for the study. The remission rate and residual disease activity of RA patients were compared according to four criteria of remission, including 2011 ACR/EULAR remission criterion, DAS28, CDAI and ACR. RESULTS: Among the 310 cases, 254 effective questionnaires were obtained. The remission rates of ACR, CDAI,ACR/EULAR and DAS28 were 15.4%, 23.2%,25.2%,38.2%, respectively.ACR criteria is the most stringent criteria, the remission rate of ACR was significantly lower than the other three criteria (P<0.05). There was no residual disease activity of ACR criteria. DAS28 criteria is the laxest criteria,the remission rate and residual disease activity of DAS28 was significantly higher than the other three criteria (P<0.05).There was no difference between CDAI and ACR/EULAR, which were more suitable for clinical practice. CONCLUSION: Among the four criteria, ACR criteria is the most stringent criteria, DAS28 criteria is the laxest criteria, The CDAI and ACR/EULAR criteria were more suitable for clinical practice.
23117243 Response to glucocorticoids at 2 weeks predicts the effectiveness of DMARD induction thera 2013 Oct OBJECTIVE: To investigate if a glucocorticoid (GC) response at 2 weeks, defined by EULAR response criteria, can predict active disease (Disease Activity Score (DAS)>2.4) at 3 months. METHODS: For this study, data of the Treatment in the Rotterdam Early Arthritis Cohort study (tREACH), an ongoing clinical trial that evaluates different induction therapies in early rheumatoid arthritis, were used. We selected patients who had a high probability of progressing to persistent arthritis (>70% based on the prediction model of Visser). All patients within the high-probability stratum, who had a baseline DAS>2.2 and a DAS assessment at 2 weeks after randomisation, were included (n=120). Besides GC response at 2 weeks, we investigated which other factors were associated with active disease (DAS>2.4) after 3 months of disease-modifying antirheumatic drug (DMARD) treatment. All variables with a p≤0.25 were assessed in our logistic regression model with backward selection. Variables were eliminated until all remaining variables had a significant association (p<0.05). RESULTS: Patients who did not respond to GC bridging therapy at 2 weeks had an overall OR of having active disease at 3 months of 10.29 (95% CI 3.34 to 31.64; p<0.001) in comparison with responders. The corrected OR was 14.00 (95% CI 3.31 to 59.21; p<0.001). Our final model predicting response at 3 months included the following variables: gender, GC response, induction therapy arms and baseline DAS, which had an explained variance of 39%. CONCLUSIONS: GC response at 2 weeks is a useful tool for recognising those patients who will probably have active disease (DAS>2.4) after 3 months of DMARD treatment.
24710131 Low-dose prednisolone treatment of early rheumatoid arthritis and late cardiovascular outc 2014 Apr 7 OBJECTIVE: To examine the long-term effects of early low-dose prednisolone use in patients with rheumatoid arthritis (RA) on cardiovascular (CV) morbidity and mortality. DESIGN: Retrieval of data from a 2-year open randomised trial comparing prednisolone 7.5 mg/day in addition to disease-modifying antirheumatic drugs (DMARDs) with DMARD therapy alone. Participants were followed for 10 years since inclusion into the original prednisolone trial or until occurrence of the studied outcomes. SETTING: Secondary level of care; six participating centres from southern Sweden; both urban and rural populations. PARTICIPANTS: Overall, 223 patients with early RA were included. The participants had no history of CV events at baseline and incident cases were identified via the Swedish Hospital Discharge and Cause of Death Registries. OUTCOMES: Composite CV events, that is, ischaemic coronary and cerebrovascular events, components of the composite CV outcome, and death. Relative HRs from Cox proportional-hazards regression models were calculated. RESULTS: Within 2041 person-years, 17 incident composite CV events occurred in 112 patients (15%) randomised to prednisolone, and 15 events of 111 patients (14%) who were assigned not to receive prednisolone. There were nine deaths (8%) in each group. The age-adjusted relative hazards (HRs; 95% CI) for the first composite CV event, first coronary event and death in the prednisolone group versus the group not treated with prednisolone were 1.8 (0.9 to 3.6), 0.98 (0.4 to 2.6) and 1.6 (0.6 to 4.1), respectively. The risk for the first cerebrovascular event showed a 3.7-fold increased relative hazard (95% CI 1.2 to 11.4) among prednisolone treated patients. CONCLUSIONS: In this inception cohort study of low-dose prednisolone use during the first 2 years of RA disease, the incidence of ischaemic coronary artery events was similar in the two treatment groups, whereas the long-term risk of ischaemic cerebrovascular events was higher in the prednisolone group. There was a trend towards reduced survival in the prednisolone group. TRIAL REGISTRATION NUMBER: ISRCTN20612367.
23819335 [Relationship of the clinical efficiency of tocilizumab therapy to the serum level of matr 2013 AIM: To evaluate the impact of tocilizumab (TCZ) therapy on the level of matrix metalloproteinase-3 (MMP-3) 4, 24, and 48 weeks after treatment initiation in relation to the clinical efficiency of TCZ therapy by the Disease Activity Score (DAS28), the Clinical Disease Activity Index (CDAI), and the Simplified Disease Activity Index (SDAI). SUBJECTS AND METHODS: Forty-two rheumatoid arthritis (RA) patients who had received 6 intravenous infusions of TCZ 8 mg/kg at a 4-week interval during permanent therapy with disease-modifying anti-rheumatic drugs (DMARD) and glucocorticosteroids (GCS) were examined. Then TCZ was discontinued and the patients continued to receive the previous therapy with DMARD and GCS. The European League Against Rheumatism (EULAR) classification criteria, as well as SDAI and CDAI were used to evaluate the efficiency of TCZ therapy. The serum concentration of MMP-3 was measured by enzyme immunoassay using the test systems (Invitrogen, USA). RESULTS: After 24 weeks of TCZ therapy (at 48 weeks following trial initiation), DAS28 was 4.69 (3.86; 5.44); the SDAI of 17.8 (10.7; 29.5) and the CDAI of 17.1 (7.2; 26.2) corresponded to moderate disease activity. At 48 weeks, DAS28 remission (< 2.6 scores) remained in 5 (11.90%) patients; SDAI (< or = 3.3 scores) and CDAI (< or = 2.8 scores) remissions did in 3 (7.1%) and 4 (9.5%) patients, respectively. There was a significant reduction in MMP-3 concentrations at 4, 24, and 48 weeks of the therapy, which was 61, 73, and 49.40% of the baseline level. ROC analysis indicated that the normalization of MMP-3 levels in RA patients at 24 weeks of TCZ therapy (a cut-off < or =16.5 ng/ml) was associated with the maintenance of remission/low disease activity from SDAI and CDAI 24 weeks after the drug use (the area under the receiver operating curve was 0.762; 95% confidence interval: 0.548-0.976). CONCLUSION: Analysis of the results of 48-week TCZ therapy suggests its ability to reduce the levels of markers of bone and cartilage destruction in patients with RA. Serum MMP-3 determination at 24 weeks of therapy may be useful in predicting the maintenance of remission/low activity from SDAI and CDAI after discontinuation of the drug.
22938792 Baseline comorbidities in patients with rheumatoid arthritis who have been prescribed biol 2013 Jan AIM: To determine whether rheumatoid arthritis (RA) patients who have been prescribed biological agents exhibit a different comorbidity burden than RA patients who take disease-modifying antirheumatic drugs (DMARDs) alone, and to understand the association between comorbidity and other variables, as well as the association between comorbidity and multimorbidity. METHODS: This observational case-control study included 114 RA patients treated with biological agents and a control group comprising 163 sex- and age-matched RA patients treated with DMARDs only. Current and previous data regarding the patients' disease activity, comorbidities, and treatments were collected. The data were analysed using bivariate and multivariate regression models. RESULTS: The patients who were prescribed biological agents exhibited poorer disease control, received more DMARDs and steroids, and underwent more total joint arthroplasties compared with the patients in the control group. However, the risk factors for cardiovascular disease and the comorbidity frequency were similar between cases and controls. The most prevalent comorbidities were hypertension, obesity, and respiratory, thyroid, and upper gastrointestinal disorders. The incidence of cardiovascular disease was low, and only 29% of the patients exhibited multimorbidities. A bivariate association of age, late diagnosis, joint replacements and a high score on the health assessment questionnaire score (HAQ) with comorbidity was observed. There were also correlations between the Charlson index and age, joint reconstructive surgery, disease activity (DAS28), and HAQ score. However, when binary logarithmic regression models were applied, only patient age remained significantly associated with comorbidity and multimorbidity [hazard ratio, 1.08; 95% confidence interval, 1.05-1.12; p<0.0005]. CONCLUSION: RA patients taking biological drugs have a comorbidity burden equivalent to those treated with DMARDs alone. Age is the main predictive factor of comorbidity in these patients.
20652272 Chronic monoarthritis and foot-drop as a paraneoplastic syndrome in prostate cancer. 2013 Jan Paraneoplastic rheumatic symptoms, caused by a malignancy, but not directly related to invasion by the tumor or its metastases are the result of a wide variety of tumor-derived biologic mediators. Recognition of paraneoplastic rheumatic syndromes is important, as it may lead to an early diagnosis of cancer. We report a 71-year-old patient with prostate cancer, presented with chronic monoarthritis of the left ankle and foot-drop. Monoarthritis and foot-drop was resistant to non-steroidal anti-inflammatory drugs and corticosteroids. After tumor resection, synovitis resolved and foot-drop disappeared almost totally.