Change In DAS28 Research Articles

Genetic variants within the MAP kinase signalling network and anti-TNF treatment response in rheumatoid arthritis patients

BackgroundRheumatoid arthritis (RA) does not always respond to available treatments, including tumour necrosis factor (TNF) antagonists. A study was undertaken to investigate whether genetic variation within genes, encoding proteins in...

Increased Interleukin 21 (IL-21) and IL-23 Are Associated with Increased Disease Activity and with Radiographic Status in Patients with Early Rheumatoid Arthritis

To investigate the levels of the T helper (Th)17-related cytokines interleukin 17A (IL-17A), IL-21, and IL-23 and their association with disease activity in rheumatoid arthritis (RA). In a longitudinal sample set from patients with early RA (< 6 months; n = 40), we measured the plasma cytokine levels of IL-17A, IL-21, and IL-23 and analyzed for correlation with disease activity in 28 joints (Disease Activity Score 28-joint count; DAS28), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and total Sharp score (TSS). In a transverse sample set of patients with chronic RA (> 8 years), using paired peripheral blood mononuclear cells and synovial fluid mononuclear cells, we investigated the cellular expression of IL-17A, IL-21, and IL-23R. Patients with early-stage RA had significantly increased plasma levels of IL-21 and IL-23, but not IL-17A, compared to patients with chronic RA and healthy volunteer controls. Plasma levels of IL-21 and IL-23 after 12 months of treatment correlated with DAS28 and ESR, but not to TSS. Changes in IL-23 plasma levels from time of diagnosis to 12 months correlated with change in DAS28 and with TSS scores at 2 years. The numbers of CD4+ T cells producing IL-21 were significantly increased in the synovial fluid of patients with chronic RA, with only marginal coexpression of IL-21 and IL-17A. Our results show a significant association between plasma levels of IL-21 and IL-23 and disease activity in RA, supporting the hypothesis that IL-21 and IL-23 are important pathogenic factors of this disease.

Are switches from oral to subcutaneous methotrexate or addition of ciclosporin to methotrexate useful steps in a tight control treatment strategy for rheumatoid arthritis? A post hoc analysis of the CAMERA study

ObjectiveTo investigate the effects of a switch from oral methotrexate (MTX) to subcutaneous MTX (scMTX) or adding ciclosporin to oral MTX with a simultaneous reduction of the MTX dose, in...

Frequency and effectiveness of dose increase of adalimumab, etanercept, and infliximab in daily clinical practice

To describe the frequency and effectiveness of dose increase of adalimumab, etanercept, and infliximab in the treatment of rheumatoid arthritis (RA) in daily clinical practice. All RA patients with a dose increase of tumor necrosis factor (TNF)-blocking therapy between January 1997 and January 2008 were selected from a register including data from RA patients starting a first TNF-blocking agent (the Dutch Rheumatoid Arthritis Monitoring registry). The primary outcome was change in Disease Activity Score in 28 joints (DAS28) at 3 months after dose increase. Secondary outcomes were the change in DAS28 at 6 months after dose increase, the European League Against Rheumatism response rates, and the percentages of patients reaching a DAS28 of ≤3.2 at 3 and at 6 months after dose increase. Furthermore, the effectiveness of dose increase was assessed for the different reasons for dose increase: nonresponse, loss of response, and partial response. During the study period, the dose was increased in 44 (12%) of the 368 adalimumab patients, 32 (8%) of the 420 etanercept patients, and 115 (36%) of the 323 infliximab patients. The change in DAS28 at 3 months and 6 months after dose increase was limited and only significant in etanercept patients at 3 months (-0.51; P = 0.035). Disease activity decreased significantly at 3 months from dose increase in the nonresponders and patients with loss of response (-0.66 and -0.99, respectively; both P = 0.001), but not in the partial responders. Although dose increase was applied in all 3 TNF-blocking agents in daily clinical practice, these results suggest that the effectiveness of dose increase is limited.

Lack of replication of genetic predictors for the rheumatoid arthritis response to anti-TNF treatments: a prospective case-only study

IntroductionWe aimed to replicate the strong associations that a recent genome wide association study (GWAS) has found between 16 single nucleotide polymorphisms (SNPs) and response to anti-tumour necrosis factor (TNF) treatment in 89 patients with rheumatoid arthritis (RA). This study is very important because, according to published simulations, associations as strong as the reported ones will mean that these SNPs could be used as predictors of response at the individual level.MethodsDisease activity score (DAS28) was evaluated in 151 anti-TNF treated patients with RA of Spanish ancestry at baseline and every 3 months thereafter. Genotypes of the 16 putative predictor SNPs were obtained by single-base extension. Association between the relative change in DAS28 and SNP genotypes was tested by linear regression. In addition, logistic regression was applied to compare genotypes in non-responders (n = 34) versus good-responders (n = 61) following the EULAR response criteria.ResultsNone of the analyses showed any significant association between the 16 SNPs and response to anti-TNF treatments at 3 or 6 months. Results were also negative when only patients treated with infliximab (66.9% of the total) were separately analyzed. These negative results were obtained in spite of a very good statistical power to replicate the reported strong associations.ConclusionsWe still do not have any sound evidence of genetic variants associated with RA response to anti-TNF treatments. In addition, the possibility we had envisaged of using the results of a recent GWAS for prediction in individual patients should be dismissed.

Genotype at the sIL-6R A358C polymorphism does not influence response to anti-TNF therapy in patients with rheumatoid arthritis

To investigate the association between genotype at the soluble interleukin 6 receptor (sIL-6R) A358C single nucleotide polymorphism (SNP, rs8192284), previously reported to correlate with soluble receptor levels, and response to anti-TNF therapy in subjects with RA. In a large cohort of Caucasian RA patients treated with anti-TNF medications (total, n = 1050; etanercept, n = 455; infliximab, n = 450; and adalimumab, n = 142), the sIL-6R A358C polymorphism was genotyped using a Taqman 5'-allelic discrimination assay. Linear regression analysis adjusted for baseline 28 joint disease activity score (DAS28), baseline HAQ score, gender and use of concurrent DMARDs was used to assess the association of genotype at this polymorphism with response to anti-TNF therapy, defined by change in DAS28 after 6 months of treatment. Analyses were performed in the entire cohort, and also stratified by an anti-TNF agent. Additional analysis according to the EULAR response criteria was also performed, with the chi-squared test used to compare genotype groups. No association between genotype at sIL-6R A358C and response to anti-TNF treatment was detected either in the cohort as a whole or after stratification by anti-TNF agent, in either the linear regression analysis or with response segregated according to EULAR criteria. This study shows that genotype at the functional sIL-6R A358C SNP is not associated with response to anti-TNF treatment in patients with RA.

Abstract 4964: Tnf- α Antagonists Improve Arterial Stiffness in Patients With Inflammatory Arthropathies: Results From a One Year Controlled Study

Introduction: The chronic inflammatory state of rheumatoid arthritis (RA), ankylosing spondylitis (AS) and psoriatic arthritis (PsA) contributes to the accelerated atherosclerosis associated with these diseases. Hypothesis: We assessed the hypothesis that one year treatment with TNF- α antagonists would improve arterial stiffness in patients with RA, AS and PsA. Methods: A total of 52 patients with RA, AS or PsA and clinical indication for anti-TNF- α therapy were included. 36 patients started with anti-TNF- α therapy and were compared with a non-treatment group of 16 patients. Aortic pulse wave velocity (aPWV) and augmentation index (AIx) were measured at baseline and after one year (Sphygmocor). Each visit also included blood samples and assessment of disease activity. Results: Values are given as mean± SD. Age of the patients in the treatment/control group was 46.2±12.2/49.0±14.1 years (p=0.21), 42.9/50.0 % (p=0.63) were females and disease duration was 11.0±9.6/11.6±10.1 years (p=0.56). Patients who started anti-TNF- α therapy had a significant decrease in aPWV (−0.53±0.13 m/s) whereas the patients in the control group had no change (+0.08±0.10 m/s, p=0.001 for between groups changes). Between groups differences for AIx were not observed (change 0.1±6.1 % and 0.2±5.7 %, p=0.95). There was no change in blood pressures, lipid levels or kidney function in any of the groups. A significant reduction in CRP and DAS28 (RA patients) was observed in the treatment group, but we did not find any significant bivariate correlations between the changes in aPWV and CRP ( ρ =0.11, p=0.55) or between changes in aPWV and DAS28 in the RA group ( ρ = −0.21, p=0.44). Conclusion: The present study shows for the first time in a comparative design that long term anti-TNF- α therapy improves aPWV in patients with RA, AS and PsA. This finding supports the idea that atherosclerosis is partly driven by inflammation, and that this process is amenable to pharmacologic intervention. Baseline value and change in key variables

Evaluation of composite measures of treatment response without acute-phase reactants in patients with rheumatoid arthritis

To evaluate composite measures of response without acute-phase reactants in RA patients. Specifically, Clinical Disease Activity Index (CDAI)-derived response criteria were compared with the European League Against Rheumatism (EULAR) response criteria, and the modified ACR (mACR) response criteria were compared to the ACR response criteria. Data from 10 108 RA patients enrolled in the Consortium of Rheumatology Researchers of North America registry were examined, including 649 patients initiating DMARD therapy. CDAI cut-off points for disease activity levels and responses were derived using receiver operating characteristic curves with the DAS28 and EULAR response criteria as gold standards. The kappa-statistics were applied to assess agreement between CDAI-derived and EULAR-defined responses, as well as ACR20 and ACR50 with mACR20- and mACR50-defined responses, respectively. For the components of the EULAR response, the derived CDAI cut-off points for DAS28 levels of 3.2 and 5.1 were 7.6 and 19.6, respectively. The derived CDAI cut-off points were 4.3 and 10.0 for DAS28 changes of 0.6 and 1.2, respectively. There were moderate to substantial agreements between CDAI-derived and EULAR responses (kappa = 0.57-0.71). Agreement of ACR20 and ACR50 with mACR20 and mACR50 responses, respectively, was excellent (kappa = 0.88-0.95). Agreement between composite measures of response without acute-phase reactants and standard measures ranged from moderate to excellent. The mACR20 and mACR50 criteria as well as CDAI-derived response criteria, can serve as composite measures of response in clinical practice and research settings without access to acute-phase reactants.

Melatonin influence on clinical and endocrine measures in early rheumatoid arthritis

Система комплексной поддержки и сопровождения научного журнала Elpub позволяет запустить двуязычный сайт журнала со встроенной системой электронной редакции в соответствии с лучшими издательскими практиками, а так же предусматривает техническую и методическую поддержку со стороны специалистов НЭИКОН.

Disease activity of rheumatoid arthritis during pregnancy: Results from a nationwide prospective study

According to common knowledge and retrospective studies, approximately 75-90% of patients with rheumatoid arthritis (RA) will improve during pregnancy. Prospective data on disease activity during pregnancy are limited. Therefore, this study aimed to prospectively determine the disease activity during pregnancy in RA patients treated in an era of new treatment options. For 84 RA patients (American College of Rheumatology criteria), a Disease Activity Score in 28 joints (DAS28) and medication use were obtained, before conception if possible, at each trimester of pregnancy and at 6, 12, and 26 weeks postpartum. Improvement and deterioration were determined by assessing changes in DAS28 and by applying the DAS28-derived European League Against Rheumatism (EULAR) response criteria. Disease activity decreased with statistical significance (P = 0.035) during pregnancy and increased postpartum. In patients with at least moderate disease activity in the first trimester (n = 52), at least 48% had a moderate response during pregnancy according to EULAR-defined response criteria. In patients with low disease activity in the first trimester (n = 32), disease activity was stable during pregnancy. Thirty-nine percent of patients had at least a moderate flare postpartum according to reversed EULAR response criteria. Less medication was used during pregnancy compared with before conception and compared with postpartum. This study demonstrates that patients achieve remission during pregnancy and deteriorate postpartum, although less frequently than previously described.

Association of the tumour necrosis factor-308 variant with differential response to anti-TNF agents in the treatment of rheumatoid arthritis

Anti-tumour necrosis factor (TNF) agents have revolutionized the treatment of patients with rheumatoid arthritis (RA). These therapies are, however, expensive and 30% of patients fail to respond. In a large cohort of Caucasian RA patients treated with anti-TNF medications (total n = 1050, etanercept n = 455, infliximab n = 450), we investigated whether genotypes of eight single nucleotide polymorphisms in the region containing the TNF gene were associated with response to anti-TNF therapy. Linear regression analyses adjusted for baseline 28 joint disease activity score (DAS28), baseline health assessment questionnaire score, gender and concurrent disease modifying anti-rheumatic drug treatment were used to assess association of these polymorphisms with treatment response, defined by change in DAS28 after 6 months. Analyses were performed in the entire cohort, and also stratified by anti-TNF agent. Association between DAS28 response and TNF-308 (rs1800629) genotype (P = 0.001) was detected across the whole cohort. After stratification by anti-TNF agent, the rare TNF-308AA genotype was associated with a significantly poorer response compared with TNF-308GG in etanercept (P = 0.001, n = 7) but not infliximab (P = 0.8, n = 17) treated patients. Conversely, the GA genotype at TNF-238 (rs361525) was associated with a poorer response to infliximab (P = 0.028, n = 40), but not etanercept (P = 0.6, n = 33). Owing to the small numbers of patients in some of the genotype groups examined, our data must be regarded as preliminary and will require replication in further large cohorts of anti-TNF-treated patients. If confirmed, our findings suggest the potential for genotype at these markers to aid selection of anti-TNF agent in patients with RA.

Efficacy and safety of abatacept or infliximab vs placebo in ATTEST: a phase III, multi-centre, randomised, double-blind, placebo-controlled study in patients with rheumatoid arthritis and an inadequate response to methotrexate

Objectives:This double-blind trial evaluated the efficacy and safety of abatacept or infliximab vs placebo. The primary objective of this study was to evaluate the mean change from baseline in Disease...

Genome-Wide Association Scan Identifies Candidate Polymorphisms Associated with Differential Response to Anti-TNF Treatment in Rheumatoid Arthritis

The prediction of response (or non-response) to anti-TNF treatment for rheumatoid arthritis (RA) is a pressing clinical problem. We conducted a genome-wide association study using the Illumina HapMap300 SNP chip on 89 RA patients prospectively followed after beginning anti-TNF therapy as part of Autoimmune Biomarkers Collaborative Network (ABCoN [Autoimmune Bio-markers Collaborative Network]) patient cohort. Response to therapy was determined by the change in Disease Activity Score (DAS28) observed after 14 wks. We used a two-part analysis that treated the change in DAS28 as a continuous trait and then incorporated it into a dichotomous trait of "good responder" and "nonresponder" by European League Against Rheumatism (EULAR) criteria. We corrected for multiple tests by permutation, and adjusted for potential population stratification using EIGENSTRAT. Multiple single nucleotide polymorphism (SNP) markers showed significant associations near or within loci including: the v-maf musculoaponeurotic fibrosarcoma oncogene homolog B (MAFB) gene on chromosome 20; the type I interferon gene IFNk on chromosome 9; and in a locus on chromosome 7 that includes the paraoxonase I (PON1) gene. An SNP in the IL10 promoter (rs1800896) that was previously reported as associated with anti-TNF response was weakly associated with response in this cohort. Replications of these results in independent and larger data sets clearly are required. We provide a reference list of candidate SNPs (P < 0.01) that can be investigated in future pharmacogenomic studies.

Psychometric properties of the Rheumatoid Arthritis Disease Activity Index (RADAI) in a cohort of consecutive Dutch patients with RA starting anti-tumour necrosis factor treatment

Objectives:To examine the psychometric properties of the self-administered Dutch Rheumatoid Arthritis Disease Activity Index (RADAI) and its short form (RADAI-SF) in patients with rheumatoid arthritis starting anti-tumour necrosis factor treatment.Method:Internal...

Comment on the use of self‐reporting instruments to assess patients with rheumatoid arthritis: The longitudinal association between the DAS28 and the VAS general health

Recently, the use of patient self-reporting instruments instead of clinical, objective measurements to assess rheumatoid arthritis (RA) patients was proposed. This assumes a constant association between disease activity and the self-reporting instruments. The objective was to explore the association (in time) between disease activity and patient perception of general health, disease activity, pain, and functional disability in patients with RA. Data of 624 newly diagnosed RA patients who completed 3 years of followup were analyzed. Cross-sectional linear regression models and longitudinal regression models were estimated, with a visual analog scale (VAS) measuring general health (VAS-GH; 0 = best, 100 = worst) as a dependent variable and the Disease Activity Score (DAS28) without the VAS-GH as an independent variable. Other dependent variables were VAS disease activity, pain, and the Health Assessment Questionnaire. The DAS28 and VAS-GH were significantly associated in RA patients (P < 0.001). However, the explained variance was low (6.7%). From diagnosis to 3 years after the diagnosis, the intercept decreased given the same regression coefficient. The longitudinal regression model showed that the VAS-GH improved during disease course independent of a change in DAS28. Analyses on the other outcome parameters showed similar results. Patients' perception of health can be different with equal disease activity, depending on the moment in the disease course. Furthermore, our results indicate that self-reported measures on functionality, disease activity, and general health cannot substitute for objective measures of disease activity in RA in longitudinal studies; subsequently, both need to be measured.

Effect of anti-TNFα treatment on circulating endothelial progenitor cells (EPCs) in rheumatoid arthritis

Abstract Rheumatoid arthritis (RA) is associated with increased cardiovascular morbidity and mortality, which may be attenuated by anti-inflammatory treatment. Endothelial progenitor cells (EPCs) have the ability to differentiate into mature endothelium and have a potentially reparative role protecting against ischemia and atherosclerosis. Objective To investigate the effect of treatment with infliximab on the number and functional capacity of endothelial progenitor cells (EPCs) in patients with RA, as a possible mechanism for reducing cardiovascular morbidity in this disorder. Methods Patients: Active seropositive RA patients ( N = 14) considered candidates for starting infliximab treatment, were recruited. Assessment, based on DAS-28, was performed before treatment and 14 days later. Peripheral blood mononuclear cells were isolated and EPC numbers evaluated by the colony-forming unit (CFU) method. Endothelial phenotyping of CFU was performed by immunofluorescence employing antibodies to Tie-2 VEGF-receptor 2, and CD31. EPC Functional properties were evaluated by fibronectin adherance. Results A significant 33.4% increase ( p < 0.001) in EPC levels was observed after infliximab. A 60% increase was noted in the EPC differentiation scale, ( p < 0.002) while a 37.6% increase was observed in mean EPC adhesion ( p < 0.001). These changes were associated with a 17.5% decrease in the DAS-28 ( p < 0.0001). A significant correlation was observed between the clinical response, reflected by changes in DAS-28 and the degree of increase in EPC CFUs. Conclusion A single dose of infliximab improved the number and functional properties of EPCs, in parallel with an early clinical effect, suggesting a possible mechanism by which anti-inflammatory treatment may reduce cardiovascular risk in RA patients.

Lack of agreement between patients' and physicians' perspectives of rheumatoid arthritis disease activity changes

Objective: To obtain information on changes in patients' satisfaction (PATSAT) and physicians' global assessment (PhGASS) with regard to rheumatoid arthritis (RA) activity fluctuations.Methods: Eighty‐eight RA outpatients out of 207 investigated were assessed for 3 months on average after the initial evaluation. PATSAT (1 = excellent to 5 = unsatisfactory), PhGASS (visual analogue scale 1–100), and the 28‐joint Disease Activity Score (DAS28) were assessed as at the first evaluation. The only prerequisite for enrolment was any therapeutic change at the first visit. Changes in PATSAT (SATCH) and PhGASS (PhGACH) were categorized and subsequently related to the DAS28 changes. Statistical evaluation was carried out by the Kruskal–Wallis test, the Mann–Whitney U‐test, and by kappa statistics.Results: To achieve a positive SATCH (n = 26/88 patients), a median DAS28 reduction of −1.06 (−25.0%) was necessary, whereas a considerably lower median increase of +0.16 (+10.5%) caused a negative SATCH. PhGASS (n = 38/88 patients) changed positively on a median DAS28 reduction of −0.82 (−16.0%), whereas it worsened at a mean DAS28 increase of +0.55 (+16.5%). Approximately 60% congruence between SATCH and PhGACH could be observed (kappa = 0.139). The DAS28 values preceding a positive SATCH and PhGACH were significantly higher (p<0.001) than before a negative change.Conclusion: The patients' perspective with respect to improvement or worsening of RA is asymmetric. In contrast to the physicians' perspective, patients require greater improvement to be satisfied and less deterioration to be dissatisfied. These results may provide additional guidance in considerations about defining response and non‐response in RA.

Fucosylation of α1-acid glycoprotein (orosomucoid) compared with traditional biochemical markers of inflammation in recent onset rheumatoid arthritis

Background: Fucosylation of α1-acid glycoprotein (AGP, orosomucoid) has previously been found to be increased in patients with rheumatoid arthritis. Furthermore, the degree of fucosylation has been suggested to reflect disease activity. Therefore, we investigated the fucosylation of AGP in 131 patients (96 women and 35 men) with recent onset rheumatoid arthritis (RA). We compared the results with traditional biochemical markers of inflammation, i.e. plasma concentrations of AGP (P-AGP), and C-reactive protein (P-CRP). Methods: AGP fucosylation measured with a novel lectin enzyme-linked immunosorbent assay (ELISA) was compared with a disease activity score (DAS28) and its components, and with P-AGP, and P-CRP at the time of diagnosis, and at a follow-up visit 1 year later. Results: Both men and women with RA had increased AGP fucosylation compared to healthy individuals. We found a weak correlation between AGP fucosylation and DAS28 only in men. In men with initially increased AGP fucosylation, the level of fucosylation correlated with the change in DAS28 during the first year following diagnosis. Conclusion: We conclude that AGP fucosylation is not superior to traditional markers of disease activity in RA. However, AGP fucosylation may give some additional information to traditional biochemical markers on the disease progression in men.

Diagnosis and management of ocular leprosy.

<h3>Objective.</h3> For patients with rheumatoid arthritis (RA), recommendations are inconclusive about whether tumor necrosis factor-α (TNF-α)-blocker therapy should be evaluated at 3 or 6 months. Biomarkers are needed to predict at 3 months which patients would benefit from further treatment because of nonoptimal response. Our objective was to investigate whether serum etanercept (ETN) concentrations and anti-ETN antibodies at 3 months are predictors of clinical response to ETN at 6 months in patients with RA in terms of European League Against Rheumatism criteria and Disease Activity Score in 28 joints (DAS28). <h3>Methods.</h3> Between 2009 and 2010, we included 19 women with active RA who were candidates for ETN therapy. Response criteria were evaluated at 3 and 6 months. Serum concentrations of ETN and anti-ETN antibodies were measured by ELISA at baseline and at 3 and 6 months. <h3>Results.</h3> Eighteen patients completed followup. Three-month ETN concentrations were lower for 6-month nonresponders than responders (p = 0.03). Three-month ETN levels correlated significantly with change in DAS28 between baseline and 6 months (r = −0.62, p = 0.006). The best predictor of response at 6 months was observed with an ETN threshold of 3.1 μg/ml at 3 months. No anti-ETN antibodies were found. <h3>Conclusion.</h3> ETN concentrations at 3 months predict response to ETN therapy at 6 months. Low ETN concentrations could explain the absence of response to ETN, suggesting that patients with low ETN levels could benefit from increased ETN dose or earlier interruption of treatment.