Disease Activity Score DAS28 Research Articles

The association between body mass index, diagnostic markers and disease activity score with progression of rheumatoid arthritis in a sample of Iraqi patients

Background: Rheumatoid arthritis (RA) is a widespread, chronic, systemically inflammatory disease which, if improperly treated, can cause deformed joints and functional disability. For best disease management, greater chances of recovery, and the avoidance of irreversible clinical and radiographic damage, RA must be diagnosed and treated as soon as possible.Objectives: The purpose of this study was to evaluate body mass index utilizing DAS and levels of diagnostic tests in rheumatoid arthritis patients.Materials and methods: 120 patients with rheumatoid arthritis (60 newly diagnosed untreated patients and 60 others under treatment) were collected from Al-Yarmouk Hospital in Baghdad and 60 control individuals. Body mass index (BMI) was measured by equation and diagnostic tests, then vitamin D3 with the COPAS 111 device. Results: The prevalence of the disease in females was 91%, while males were 9%. Diagnostic tests recorded clear significance (p < 0.05) differences between patients and healthy persons, and it increased with the severity of the disease. Additionally, patients' levels of vitamin D3 reduced significantly when compared to controls, and there was a significant disparity between patients and healthy participants' sugar levels, and the BMI correlated with disease activity.Conclusions: The current study concluded that there is a relationship between weight gain and disease severity, that diagnostic tests increased in patients, and that vitamin D3 can be used as a diagnostic marker for rheumatoid arthritis. Keywords: Body mass index (BMI),disease activity score DAS-28, diagnostic marker.

IL-40: A New B Cell-Associated Cytokine Up-Regulated in Rheumatoid Arthritis Decreases Following the Rituximab Therapy and Correlates With Disease Activity, Autoantibodies, and NETosis.

BackgroundInterleukin 40 (IL-40) is a newly identified B cell-associated cytokine implicated in humoral immune responses and B cell homeostasis. As B cells play a pivotal role in autoimmunity, we investigated the function of IL-40 in rheumatoid arthritis (RA).MethodsIL-40 expression was determined in the synovial tissue from RA and osteoarthritis (OA) patients. IL-40 was analysed in the serum/synovial fluid of patients with RA (n=50), systemic lupus erythematosus (SLE, n=69), OA (n=44), and healthy controls (HC, n=50). We assessed the changes of IL-40 levels in RA patients following the B cell depletion by rituximab (n=29) or after the TNF inhibition by adalimumab (n=25). We examined the relationship between IL-40, disease activity, autoantibodies, cytokines, and NETosis markers. Effect of IL-40 on synovial fibroblasts was determined.ResultsIL-40 was overexpressed in RA synovial tissue, particularly by synovial lining and infiltrating immune cells. The levels of IL-40 were up-regulated in the synovial fluid of RA versus OA patients (p<0.0001). Similarly, IL-40 was increased in the serum of RA patients compared to HC, OA, or SLE (p<0.0001 for all) and decreased after 16 and 24 weeks (p<0.01 and p<0.01) following rituximab treatment. No significant effect of adalimumab on IL-40 was observed. IL-40 levels in RA patients correlated with rheumatoid factor-IgM and anti-cyclic citrullinated peptides (anti-CCP) in the serum (p<0.0001 and p<0.01), as well as in the synovial fluid (p<0.0001 and p<0.001). Synovial fluid IL-40 was also associated with disease activity score DAS28 (p<0.05), synovial fluid leukocyte count (p<0.01), neutrophil attractants IL-8 (p<0.01), MIP-1α (p<0.01), and markers of neutrophil extracellular traps externalization (NETosis) such as proteinase 3 (p<0.0001) and neutrophil elastase (p<0.0001). Synovial fibroblasts exposed to IL-40 increased the secretion of IL-8 (p<0.01), MCP-1 (p<0.05), and MMP-13 (p<0.01) compared to the unstimulated cells.ConclusionsWe show the up-regulation of IL-40 in RA and its decrease following B cell depleting therapy. The association of IL-40 with autoantibodies, chemokines, and markers of NETosis may imply its potential involvement in RA development. Moreover, IL-40 up-regulates the secretion of chemokines and MMP-13 in synovial fibroblasts, indicating its role in the regulation of inflammation and tissue destruction in RA.

Novel aspects of the activation of NADPH oxidase in neutrophils of rheumatic patients on biological therapy

The relationship between inflammation and formation of reactive oxygen species (ROS) is still not completely understood and excessive inflammatory reaction is attributed to increased yet also to reduced ROS formation. To compare ROS formation in severe and low inflammation, neutrophil oxidative burst was analyzed in rheumatic patients before and during therapy with TNFα- or interleukin-6 receptor-neutralizing antibodies.Intracellular and extracellular ROS productions were evaluated on the basis of luminol- and isoluminol-enhanced chemiluminescence in isolated peripheral neutrophils. Disease activity score DAS28 and platelet to lymphocyte ratio were used as markers of arthritis activity and the intensity of systemic inflammation.Biological therapy effectively reduced the intensity of inflammation. Of the twenty-six patients studied eighteen achieved remission or low disease activity. Highly active arthritis persisted only in one patient, though prior to the therapy it was evident in all subjects tested. In patients receiving biological therapy, intracellular chemiluminescence was significantly higher than in patients before this therapy; ROS produced by neutrophils extracellularly were not affected.The increased ROS formation associated with reduced inflammation supports the need to revise the view of the role of ROS in inflammation - from toxic agents promoting inflammation towards a more complex view of ROS as regulators of immune pathways with inflammation-limiting capacity. From this perspective, the interference with neutrophil-derived oxidants may represent a new mechanism involved in the anti-inflammatory activity of biological therapy.

The relationship between US7 ultrasound joint scoring system and disease activity score DAS28 in rheumatoid arthritis: A study in Indian population

Introduction: US7 (7 joint ultrasound score) is an emerging ultrasound (US) joint scoring system for the assessment of disease activity in patients with Rheumatoid Arthritis (RA). Methods and Material: The study was conducted at a tertiary care center in Southern India. Sixty-two patients of RA were recruited for this cross-sectional observational study. Patients' clinical & laboratory parameters were used to calculate the disease activity score DAS28. Grayscale and Power Doppler Ultrasound (GSUS & PDUS) were performed to calculate US7 score.Statistical analysis used: Spearman's rank-order correlation, Pearson interclass correlation and ROC (receiver operating characteristic) curve analysis were performed. Results: Median DAS28 value was 4.04 with one patient in clinical remission. There was a statistically significant positive correlation (r=0.262) between synovitis by GSUS score & DAS 28 (p-value = 0.040) and synovitis by PDUS score and DAS 28 (r=0.340, p-value = 0.004). No significant correlation was found between DAS28 and tenosynovitis or erosions score. ROC curve analysis yielded the p values of 0.04 and 0.004 for synovitis by GSUS and synovitis by PDUS respectively in differentiating between the patients with low (DAS groups 1 & 2) and high disease activity (3 & 4). Conclusions: There is good correlation of the synovitis component of US7 score with DAS28. However, relationship of tenosynovitis and erosions with disease activity is questionable according to our results. An 'abbreviated US7' score with detection of only synovitis may be more suitable. This requires further validation.

Comorbidities in rheumatic arthritis.

ObjectivesRheumatoid arthritis (RA) is one of the most common systemic inflammatory diseases, but its etiology is still not fully known. The aim of this preliminary study was to assess what particular comorbidities are involved in the progression of RA and determine the influence that the aforementioned diseases have on each other.Material and methodsForty patients with diagnosed RA according to EULAR/ACR criteria from 2010 were included in the study. The majority of the group was female (n = 35; 87.5%). Patients were tested using routine laboratory and imaging methods allowing diagnosis and assessment of disease activity. Dual energy X-ray absorptiometry was also evaluated for mineral density. The activity of the disease was assessed using the disease activity score DAS28 (ESR) and SDAI (Simplified Disease Activity Index).ResultsAmong studied patients, based on the DAS28 index, 9 patients were in the remission phase (22.5%) and 12 (30%) had high disease activity. Increased values of CRP were observed in the majority of patients (65%). The group analysis demonstrated the most common comorbidities in patients with RA, as follows: hypertension (n = 14; 35%) and osteoporosis or osteopenia (n = 13; 32.6%).ConclusionsPatients with rheumatoid arthritis (RA) are more susceptible to developing hypertension and osteoporosis. We did not observe a significant association between other comorbidities and activity of RA. The next study will assess a larger number of patients.

Activity of rheumatoid arthritis correlates with oral inflammatory burden.

To study oral health in patients with rheumatoid arthritis (RA) with emphasis on disease activity and treatment of RA. In this prospective cohort study 81 RA patients [53 early untreated RA (EURA) and 28 chronic RA (CRA) patients with inadequate response to synthetic disease modifying antirheumatic drugs (DMARDs)], underwent rheumatological [Disease Activity Score (28-joint) DAS28] and dental examinations [Total Dental Index (TDI), Decayed Missing Filled Teeth (DMFT) and Decayed Missing Filled Surfaces (DMFS)]. For controls, 43 volunteers were examined. After the examinations, EURA patients started treatment with synthetic DMARDs, oral and intra-articular glucocorticoids. CRA patients were candidates for biological DMARDs. The patients were re-examined mean 16 months later. Results were analyzed with descriptive statistics and logistic regression. TDI was higher in both RA groups at baseline compared to controls [EURA: 2 (2-3); CRA: 2 (1-3); controls 1 (1-3), p = 0.045]. DMFT [rs 0.561 (p = 0.002)] and DMFS [rs 0.581 (p = 0.001)] associated with DAS28 at baseline in CRA patients. After follow-up, DAS28 associated positively with DMFT [rs 0.384 (p = 0.016)] and DMFS [rs 0.334 (p = 0.038)] in EURA patients; as well as in CRA patients DMFT [rs 0.672 (p = 0.001)], DMFS [rs 0.650 (p = 0.001)]. RA patients already in the early phase of the disease had poorer oral health compared to controls. The caries indices associated with the activity of RA in both patient groups. Oral status may thus contribute to the development and further relate to the activity of RA.

Inflammatory biomarkers in saliva and serum of patients with rheumatoid arthritis with respect to periodontal status

Objective: To study prospectively the association of salivary and serum matrix metalloproteinase (MMP)-8, tissue inhibitor of MMPs (TIMP)-1 and interleukin (IL)-6 with periodontal and systemic inflammation in rheumatoid arthritis (RA). We hypothesized that biomarker concentrations reflect inflammation.Methods: Fifty three early untreated RA (ERA) and 28 chronic RA (CRA) patients, underwent rheumatological and dental examinations at baseline and one year later after starting first conventional or biological disease modifying antirheumatic drug. We included 43 control subjects. Saliva and serum samples were analyzed for MMP-8, TIMP-1 and IL-6. Periodontal health was assessed by bleeding on probing (BOP), pocket depth (PD) and periodontal inflammatory burden index (PIBI); RA disease activity was assessed by disease activity score DAS28. Joint destruction was analyzed by the modified Sharp-van der Heijde (SHS) method.Results: Serum MMP-8 (p < .001; p < .001) and IL-6 (p < .001; p = .002) were significantly higher in CRA vs. other study groups during the study. Salivary MMP-8 (p = .010) and IL-6 (p = .010) were significantly higher in ERA vs. other study groups at baseline. Salivary MMP-8 was associated with periodontal parameters.Conclusion: Elevated serum concentrations of MMP-8 and IL-6 in CRA patients reflected chronic RA, while elevated salivary concentrations of MMP-8 levels in ERA patients reflected increased periodontal inflammation.Key messagesConcentrations of inflammatory biomarkers in serum and saliva were different between patients with RA and healthy controls.Concentrations of MMP-8 and of IL-6 in serum were elevated in patients with chronic RA reflecting joint inflammation and the burden of established RA.Concentrations of MMP-8 in saliva was elevated already at the early stage of RA and the level of salivary MMP-8 was associated with poor periodontal health both in patients with early and in those with chronic RA.

Relationship between serum calprotectin (S100A8/9) and clinical, laboratory and ultrasound parameters of disease activity in rheumatoid arthritis: A large cohort study.

BackgroundCalprotectin may be a sensitive biomarker of rheumatoid arthritis (RA) disease activity.ObjectivesIn the current study, we investigated whether calprotectin is a better biomarker than CRP for predicting clinical activity and ultrasound parameters in patients with RA.MethodsA total of 160 patients with RA underwent clinical (swollen joint count—SJC, tender joint count—TJC, Disease Activity Score—DAS28, Clinical Disease Activity Index—CDAI, and simplified Disease Activity Index—SDAI) and ultrasound (German US7) examination. Clinical and laboratory measures were correlated with ultrasound findings using Spearman´s correlation coefficient. Differences in serum calprotectin levels in patients with variable disease activity according to the DAS28-ESR and CDAI scores were assessed using ANOVA. Multivariate regression analysis was used to determine the predictive values of calprotectin, CRP and SJC for CDAI and PD US synovitis scores.ResultsSerum calprotectin was significantly associated with DAS28-ESR (r = 0.321, p<0.001), DAS28-CRP (r = 0.346, p<0.001), SDAI (r = 0.305, p<0.001), CDAI (r = 0.279, p<0.001) scores and CRP levels (r = 0.556, p<0.001). Moreover, calprotectin was significantly correlated with GS (r = 0.379, p<0.001) and PD synovitis scores (r = 0.419, p<0.001). The multivariate regression analysis showed that calprotectin is a better predictor of the CDAI score and PD US synovitis than CRP.ConclusionsThe results of this study support an additional role of calprotectin in assessing inflammatory activity in patients with RA.

Effect of early treatment with disease-modifying anti-rheumatic drugs and treatment adherence on disease outcome in rheumatoid arthritis patients

Aim of the workTo evaluate the effects of early and regular treatment with Disease Modifying Anti-Rheumatic Drugs (DMARDs) on disease outcome in rheumatoid arthritis (RA) patients and factors affecting adherence to treatment. Patients and methodsSixty-four RA patients (83% females, mean age 42.9±11.9 and disease duration 4.5±2years) were divided into Group A (n=31) who received DMARDs within 6months of symptom onset and Group B (n=33) who received DMARDs later in the disease course. Patients were assessed by the disease activity score DAS28, the Modified Health Assessment Questionnaire-Disability Index (MHAQ-DI), the Physical Component Summary (PCS) and Mental Component Summary (MCS) of the Short Form-36 and scoring of radiological damage by modified Larsen’s method. Adherence was assessed by self-report and physician judgment. A questionnaire including the most important factors that may affect early and regular treatment by DMARDs/appointment keeping of follow up visits was administered to the patients. ResultsThe adherence rate was 62.5%. Group A patients had significantly lower DAS28, MHAQ-DI, radiological scores (P=0.001 for all), higher PCS (P=0.001) and MCS (P=0.003) scores than group B patients. Among groups A and B, adherent patients had significantly lower DAS28 (P=0.001 for both) and higher PCS (P=0.002 and 0.04, respectively) than non-adherent patients. Rural residence, lack of awareness about the disease and lack of belief in medication effectiveness were the most important factors associated with non-adherence (p=0.04, 0.03 and 0.045, respectively). ConclusionEarly treatment and adherence to DMARDs have an important impact on disease outcome in RA patients.

Serum Adenosine Deaminase Level is High But Not Related with Disease Activity Parameters in Patients with Rheumatoid Arthritis

Serum adenosine deaminase (ADA) has been previously proposed to predict disease activity in patients with rheumatoid arthritis (RA). The aim of this study was to investigate the level of serum ADA, and the relationship between ADA and disease activity markers, in a group of patients with RA.A hundred and 10 patients with a diagnosis of RA were recruited from outpatient clinic of Rheumatology Unit. Demographic properties comprising age, gender, disease duration and drugs were recorded. Disease activity based on disease activity score (DAS)28-erythrocyte sedimentation rate (ESR) and DAS28- C reactive protein (CRP,) ESR, CRP levels, as well as pain by visual analog scale and rheumatoid factor (RF) were recorded. Serum ADA levels (IU/L) were determined in all RA patients and in 55 age and sex similar healthy control subjects.Ninety-six female and 14 male RA patients with a mean age of 54.32±11.51, and with a mean disease duration of 11.5±9.13 years were included to the study. The control group comprised of 48 female and 7 male healthy subjects. 35.5% of the patients were on methotrexate (MTX) and 64.5% of patients were on combined DMARDs or combined MTX and anti-TNF therapies. The mean serum ADA level was statistically higher in RA patients than in control subjects (27.01±10.6 IU/L vs 21.8 ±9.9 IU/L). The mean values of ESR (23.2±14.8 mm/h), CRP (1.71±1.11mg/dL), pain by VAS (37.2±27.1), DAS28-ESR (2.72±0.77), DAS28 CRP (1.37±0.5) were not correlated with ADA levels (p>0.05).Our results have shown that serum ADA levels are higher in RA patients than in controls but were not related with any of the disease activity markers. We conclude that ADA in the serum may not be a reliable biochemical marker to predict disease activity in patients with RA.

Adalimumab decreases aortic stiffness independently of its effect in disease activity in patients with rheumatoid arthritis.

Rheumatoid arthritis (RA) is associated with increased cardiovascular morbidity and mortality attributed to traditional cardiovascular risk factors and/or the chronic systemic inflammation. We investigated the effect of a TNF antagonist (adalimumab-ADA) on aortic stiffness in RA patients. We studied 18 RA patients with active disease despite therapy with disease modifying antirheumatic drugs (DMARDs), treated with ADA (alone or in combination with DMARDs) for 12 weeks. Disease activity markers as well as aortic stiffness indices (carotid-femoral pulse wave velocity-PWV, augmentation index-AIx), were measured at baseline and at the end of treatment. Eighteen RA patients treated with methotrexate (MTX) were included as controls. Patients were categorized as responders (decrease of Disease Activity Score-DAS28 > 1.2) or nonresponders. There was a statistically significant decrease in PWV (from 8.18 ± 2.03 to 7.01 ± 1.78 m/s, p = 0.00006) and DAS28 (from 6.65 ± 1.22 to 4.69 ± 1.46, p = 0.00007) in RA patients treated with ADA. The decrease in PWV was observed both in responders (n = 12) and nonresponders (n = 6). Multivariate analysis showed that the decrease of PWV was independent of changes in disease activity or other parameters. There was no significant change in PWV in patients treated with MTX (from 8.87 ± 1.91 to 8.41 ± 2.17, p = 0.29). No significant change in AIx or traditional cardiovascular risk factors was observed. Treatment with ADA significantly reduced aortic stiffness in RA patients regardless of their response to therapy. These findings imply a direct protective effect of ADA in vascular wall in RA patients.

FRI0321 The Dynamics of Response to Rituximab in Rheumatoid Arthritis Patients with Moderate Disease Activity and Inadequate Response to Inhibitors of Tumor Necrosis Factor. Data from 3-Year REPEAT Study

BackgroundIn recent years, emphasis has shifted in rheumatoid arthritis (RA) to early intervention in the disease course. We have shown that patients with MDA should be further divided in three...

AB0284 The Diagnostic Utility of Anti-Mutated Citrullinated Vimentin Antibodies, Anti-Cyclic Citrullinated Peptide Antibodies and Rheumatoid Factor in Rheumatoid Arthritis

BackgroundAntibodies against citrullinated peptides have gained special importance in the diagnosis of rheumatoid arthritis (RA) (1,2).ObjectivesThis study aims to investigate the diagnostic sensitivity and specificity of anti-mutated citrullinated vimentin (anti-MCV)...

Temporal summation of pain and ultrasound Doppler activity as predictors of treatment response in patients with rheumatoid arthritis: protocol for the Frederiksberg hospitals Rheumatoid Arthritis, pain assessment and Medical Evaluation (FRAME-cohort) study

IntroductionChronic pain is common in rheumatoid arthritis (RA) and may still persist despite regression of objective signs of inflammation. This has led researchers to hypothesise that central pain sensitisation may...

THU0126 Multicenter retrospective study: Response to tocilizumab in clinical practice is not influenced by the number of previous biotherapy or by association with a DMARD

BackgroundTocilizumab (TCZ) is an effective treatment in rheumatoid arthritis (RA). The TCZ is indicated in failure of conventional DMARDs or after failure of first anti-TNF. Few factors are predictive of...

THU0113 Predictive factors of response to rituximab therapy modify the accelerated atherosclerosis in patients with rheumatoid arthritis

BackgroundIncreased cardiovascular mortality has been associated with rheumatoid arthritis (RA). There are reports indicating that tumor necrosis factor blockers may exert favourable but transient effects on lipid profile, flow mediated...

THU0163 Disease Flares Predict the Change to Second Line Therapy in Rheumatoid Arthritis: 9-Year Data from a Longitudinal Observational Study

BackgroundThe role of disease worsening or flares in taking important clinical decisions, such as dose adjustments or treatment change, is poorly understood in patients suffering from severe RA treated with...

AB1283 Nuclease serum and IGG activity in patients with early rheumatoid arthritis

BackgroundRheumatoid arthritis (RA) is one of the most common causes of chronic arthritis that results in severe joint damage and a shorter life span (1). Although the molecular mechanisms involved...

AB0237 Joints count in rheumatoid arthritis: a correlation study between 3 clinicians and ultrasound joints count and the impact on disease activity

BackgroundTender and swollen joints count (TJC and SJC) are necessary to calculate the disease activity score DAS28 and to appreciate rheumatoid arthritis (RA) activity. Their accounting is very subjective and...

FRI0509 Validation of a novel photo optical imaging (lightscan) in patients with rheumatoid arthritis and osteoarthritis using musculoskeletal ultrasound as reference

BackgroundThe lightscan is a novel imaging technology to assess inflammatory activity in proximal interphalangeal (PIP) joints.ObjectivesTo compare the lightscan method with musculoskeletal ultrasound (US) and the clinical disease activity score...