Assessment Of Rheumatoid Arthritis Activity Research Articles

Artificial Intelligence Quantification of Enhanced Synovium Throughout the Entire Hand in Rheumatoid Arthritis on Dynamic Contrast-Enhanced MRI.

Challenges persist in achieving automatic and efficient inflammation quantification using dynamic contrast-enhanced (DCE) MRI in rheumatoid arthritis (RA) patients. To investigate an automatic artificial intelligence (AI) approach and an optimized dynamic MRI protocol for quantifying disease activity in RA in whole hands while excluding arterial pixels. Retrospective. Twelve RA patients underwent DCE-MRI with 27 phases for creating the AI model and tested on images with a variable number of phases from 35 RA patients. 3.0 T/DCE T1-weighted gradient echo sequence (mDixon, water image). The model was trained with various DCE-MRI time-intensity number of phases. Evaluations were conducted for similarity between AI segmentation and manual outlining in 51 ROIs with synovitis. The relationship between synovial volume via AI segmentation with rheumatoid arthritis magnetic resonance imaging scoring (RAMRIS) across whole hands was then evaluated. The reference standard was determined by an experienced musculoskeletal radiologist. Area under the curve (AUC) of receiver operating characteristic (ROC), Dice and Spearman's rank correlation coefficients, and interclass correlation coefficient (ICC). A P-value <0.05 was considered statistically significant. A minimum of 15 phases (acquisition time at least 2.5 minutes) was found to be necessary. AUC ranged from 0.941 ± 0.009 to 0.965 ± 0.009. The Dice score was 0.557-0.615. Spearman's correlation coefficients between the AI model and ground truth were 0.884-0.927 and 0.736-0.831, for joint ROIs and whole hands, respectively. The Spearman's correlation coefficient for the additional test set between the model trained with 15 phases and RAMRIS was 0.768. The AI-based classification model effectively identified synovitis pixels while excluding arteries. The optimal performance was achieved with at least 15 phases, providing a quantitative assessment of inflammatory activity in RA while minimizing acquisition time. 3 TECHNICAL EFFICACY: Stage 2.

Relationship between Clinical, Serological and Ultrasound Assessment of Rheumatoid Arthritis Activity

Abstract Background Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammation of synovial tissue that leads to damage of cartilage and bone, resulting in irreversible joint destruction. Aim of the Work Our study’s aim was to assess the relationship between systematic ultrasound (US) evaluation using 7-joint and 12-joint scores and both clinical and serological evaluations in the determination of disease activity in rheumatoid arthritis patients. Also, we assessed the difference between both scores to know which is more accurate in assessing disease activity. Patients and Methods It was a cross sectional study that was carried out on fifty-five Egyptian RA patients diagnosed according to the 2010 American College of Rheumatology (ACR)/EULAR criteria. Patients were recruited from the rheumatology outpatient clinic at Ain Shams university hospital. Results Regarding 7-joint score parameters, mean and standard deviation for GS synovitis was 5.72 ± 4.44, PD synovitis was 3.74 ± 5.24, GS tenosynovitis was 1.15 ± 1.68, PD tenosynovitis was 1.76 ± 3.44 and erosions 1.07 ± 1.37. Regarding the examined areas for 7-joint score, wrist dorsal synovitis was the most common synovitis (98%), 2nd metacarpo-phalangeal joint (56%) then 2nd metatarso-phalangeal joint (49%). Wrist dorsal tenosynovitis (36%) was the most frequent tenosynovitis. Radial (33%), dorsal erosions (18%) of 2nd metacarpo-phalangeal joint and radial erosions (13%) of 5th metatarso-phalangeal joint were the most common erosions found. Our study detected significant positive correlation (P value &amp;lt;0.05 and positive correlation coefficient) between majority of 7-joint and 12-joint score parameters (both GS and PD) and clinical disease activity variables, ESR, CRP and platelet count. Our study showed highly significant positive correlation (P value &amp;lt;0.01 and positive correlation coefficient) between all parameters of 7-joint and 12-joint scores. We found that 12 joint score is slightly better than 7 joint score in accuracy and sensitivity in assessing rheumatoid arthritis disease activity despite being more time-consuming. Conclusion The 7-joint and 12-joint ultrasound scores were simple and practical sum scoring systems for use in the detection of synovitis in patients with RA and in assessment of disease activity in synovium. The correlations between the clinical disease activity indices, ESR, CRP, platelet count and components of the 7-joint and 12-joint scores may indicate their value in assessment of disease activity and severity up to date. The composite score (Combined synovitis score) for 12-joint score was significantly differentiating between moderate-severe patient groups (classified according to DAS28) with P value 0.029, so 12-joint score was better in identifying minimal difference in disease activity despite being time-consuming.

A prospective observational cohort study of the efficacy of tofacitinib plus iguratimod on rheumatoid arthritis with usual interstitial pneumonia.

This study aims to assess the efficacy of tofacitinib (TOF) plus iguratimod (IGU) in rheumatoid arthritis (RA) with usual interstitial pneumonia (UIP) (RA-UIP). This was a prospective observational cohort, single-center study. Data from 78 RA-UIP patients treated with TOF plus IGU, IGU plus conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs), and csDMARDs were analyzed. Clinically relevant responses in RA activity assessment, pulmonary function tests (PFTs), and high-resolution computed tomography (HRCT) assessment at baseline and follow-up were compared between groups to evaluate the efficacy of TOF plus IGU. A total of 78 patients were followed up for at least 6 months after treatment. There were significant changes in sedimentation rate (ESR), C reactive protein (CRP), and disease activity score (DAS) 28-CRP during the follow-up within each treatment group, but there was no statistically significant difference between the two groups. After 6 months of TOF plus IGU treatment, forced vital capacity (FVC)% (84.7 ± 14.7 vs. 90.7 ± 15.4) and HRCT fibrosis score (7.3 ± 3.4 vs. 7.0 ± 5.6) showed a significant improvement compared to the csDMARDs group (P = 0.031, P = 0.015). The TOF plus IGU-treated patients had a significantly higher regression and lower deterioration than the csDMARDs-treated patients (P = 0.026, P = 0.026) and had a significantly higher response (regression + stability), with overall response rates of 66.7% (16/24) vs. 35.7% (10/28) (P = 0.027), respectively. Our results indicate that TOF plus IGU can simultaneously relieve RA and RA-UIP and be better than the csDMARDs with a higher response rate in RA-UIP, which may be a potential choice for "dual treat-to-target".

Deep learning-based automatic scoring models for the disease activity of rheumatoid arthritis based on multimodal ultrasound images.

We aimed to investigate the value of deep learning (DL) models based on multimodal ultrasonographic (US) images to quantify RA activity. Static greyscale (SGS), dynamic greyscale (DGS), static power Doppler (SPD) and dynamic power Doppler (DPD) US images were collected and evaluated by two expert radiologists according to the EULAR-OMERACT Synovitis Scoring system. Four DL models were developed based on the ResNet-type structure, evaluated on two separate test cohorts, and finally compared with the performance of 12 radiologists with different levels of experience. In total, 1244 images were used for the model training, and 152 and 354 for testing (cohort 1 and 2, respectively). The best-performing models for the scores of 0/1/2/3 were the DPD, SGS, DGS and SPD models, respectively (Area Under the receiver operating characteristic Curve [AUC] = 0.87/0.95/0.74/0.95; no significant differences). All the DL models provided results comparable to the experienced radiologists on a per-image basis (intraclass correlation coefficient: 0.239-0.756, P < 0.05). The SPD model performed better than the SGS one on test cohort 1 (score of 0/2/3: AUC = 0.82/0.67/0.95 vs 0.66/0.66/0.75, respectively) and test cohort 2 (score of 0: AUC = 0.89 vs 0.81). The dynamic DL models performed better than the static ones in most of the scoring processes and were more accurate than the most of senior radiologists, especially the DPD model. DL models based on multimodal US images allow a quantitative and objective assessment of RA activity. Dynamic DL models in particular have potential value in assisting radiologists to improve the accuracy of RA US-based grading.

Evaluation of circulating miR-16-5p and miR-223-5p in association with musculoskeletal ultrasonography seven-joint score in the assessment of rheumatoid arthritis activity

Rheumatoid arthritis (RA) is characterized by ongoing joint destruction. MicroRNAs (miRs) are blood-based biomarkers linked to RA pathogenesis. The musculoskeletal ultrasonography seven-joint score (US7) is an objective tool to assess RA activity. We aimed to evaluate miR-223 and miR-16 roles in monitoring RA activity and to investigate if there is a link between their plasma levels and US7 score. This study enrolled 76 RA patients classified according to Disease Activity Score 28-joint count with erythrocyte sediment rate (DAS28-ESR) to inactive cases (n = 38) and active cases (n = 38). Each patient's joint was scored for synovial proliferation (gray-scale ultrasound 'GSUS7') and vascularization (power Doppler ultrasound 'PDUS7'). Real-time quantitative PCR was used to measure the expression levels of miR-16 and miR-223 in plasma. When compared to inactive group, the active group revealed significant upregulation of miR-16 and miR-223, (P = 0.001 and P = 0.02, respectively). miR-16 and miR-223 levels were correlated with synovitis PDUS7 (r = 0.34, p < 0.01 and r= 0.25, P = 0.03, respectively). miR-16 was also positively correlated with synovitis GSUS7 (r= 0.42, p < 0.001). miR-223 upregulation discriminated active from inactive RA patients at AUC = 0.64, with 76% sensitivity and 50% specificity at cutoff > 2.8-fold change), whereas miR-16 distinguished the two groups at AUC = 0.78 with 87% sensitivity and 53% specificity at cutoff >38.27-fold change. In conclusion, upregulated miR-16 may have more potential to serve as activity biomarkers than miR-223 in RA. The miR-16 level was linked to synovitis GSUS7 and synovitis PDUS7 changes but miR-223 only linked to synovitis PDUS.

Relationship between plasma fibrinogen degradation products(FDP) and D-dimer levels and disease activity in rheumatoid arthritis: A STROBE compliant article.

In this study, we aimed to investigate whether fibrinogen degradation products(FDP)and D-dimer could be used as serological indicators of rheumatoid arthritis(RA) activity, such as erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and platelets (PLT). A total of 112 consecutive patients with RA between July 2018 and July 2020 were divided into moderate and high disease activity groups (disease activity score 28(DAS28) > 3.2, n = 60) and low disease activity and remission groups (DAS28≤3.2, n = 52). A total of 50 healthy volunteers were included in the control group, and FDP and D-dimer levels were compared across the three groups. The correlations of FDP and D-dimer levels with ESR, CRP, PLT, and DAS28 were analyzed. Analyses of the receiver operating characteristic(ROC) curves and area under the ROC curve (AUC) of FDP, D-dimer, ESR, CRP, and PLT levels were performed. FDP and D-dimer levels were significantly higher in the high-activity compared to the low-activity and remission (P < .001), and the control (P < .001). No significant differences in FDP and D-dimer were observed between the low-activity and remission and the control (P > .05). FDP and D-dimer levels were positively correlated with ESR, CRP, PLT, and DAS28 (all P < .001). The ROC curves showed that the FDP and D-dimer levels could be used to evaluate the RA activity (all P < .001). The AUC of FDP was significantly larger than that of PLT (P = .047). FDP and D-dimer can be used as supplementary serological indicators to assess RA activity, in addition to ESR, CRP, and PLT.

C-Reactive Protein to Albumin Ratio and Albumin to Fibrinogen Ratio in Rheumatoid Arthritis Patients

Objective: the albumin to fibrinogen ratio (AFR) and the C-reactive protein (CRP) to albumin ratio (CAR) have been proposed as markers of systemic inflammation. The goal of this study was to differentiate rheumatoid arthritis (RA) patients from healthy people and to study the association between AFR/CAR and DAS28 in RA.Patients and methods. A case control study including 30 RA patients and 30 healthy controls was performed. Fibrinogen, albumin, CRP and erythrocyte sedimentation rate (ESR) were measured. We calculated CAR and AFR in each group and compared them. Correlations of AFR, and CAR with disease activity were examined. Receiver operation characteristic (ROC) curves of AFR and CAR were also used to detect cutoffs for disease activity assessment.Results and discussion. CAR was higher while AFR was lower in RA patients than in control group. ROC curve analyses showed that CAR can be used to detect disease activity of RA at cut off 2.66 with sensitivity 81.3% and specificity 64.3% with an area under the curve (AUC) 0.78. So, CAR was a fair parameter to discriminate disease activity among RA patients. AFR has AUC 0.62, sensitivity 87.5% and specificity 42.9% at cutoff value 5.96. So, in our group AFR was a poor indicator to discriminate disease activity among RA patients.Conclusion. AFR and CAR have been recently proposed as inflammatory markers for assessment of disease activity in RA. AFR and CAR are simple, and inexpensive biomarkers, they also can be rapidly evaluated. CAR was found to be a fair parameter to depict disease activity in RA patients. AFR poorly depicted RA activity.

Reappraisal of bone scintigraphy as a new tool for the evaluation of disease activity in patients with rheumatoid arthritis

We aimed to compare the reliability of bone scintigraphy (BS) and fluorine-18-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)—derived parameters in the detection of active arthritis in 28-joint areas and evaluate the reliability of joint counts between BS and clinical assessment in patients with rheumatoid arthritis (RA). We enrolled 106 patients (67 in the development group and 39 in the validation groups) with active RA who underwent BS, 18F-FDG PET/computed tomography (CT), and clinical evaluation of disease activity. We compared the results of BS-derived joint assessment with those of PET-derived and clinical joint assessments. Subsequently we developed a disease activity score (DAS) using BS-positive joints and validated it in an independent group. The number of BS-positive joints in 28-joint areas significantly correlated with the swollen /tender joint counts (SJC/TJC) and PET-derived joint counts. A BS uptake score of 2 (strong positive) was significantly more sensitive compared with a BS uptake score of 1 (weak positive) in detecting a PET-positive joint among the 28-joints. After conducting multivariate analyses including erythrocyte sediment rate (ESR) and patient global assessment (PGA) in addition to BS-derived parameters, BS/DAS was obtained as follows: 0.056 × number of BS-positive joints in 28 joints + 0.012 × ESR + 0.030 × PGA. A significant correlation between BS/DAS and DAS28-ESR was confirmed in the validation group. Strong positive uptake of BS is sensitive and reproducible for the detection of active joints, and can complement the clinical assessment of disease activity in RA.

Application of Automated Hand Ultrasound Scanning and a Simplified Three-Joint Scoring System for Assessment of Rheumatoid Arthritis Activity

Ultrasound can be used to objectively diagnose and evaluate disease activity in patients with rheumatoid arthritis (RA). We aimed to determine the value of a new automated hand ultrasound (AHUS) scanning device and a simplified 3-joint ultrasound scoring system (US3) in detecting synovitis in RA. We compared AHUS and traditional ultrasound (US) scanning in detecting synovial hyperplasia (SH), joint effusion, bone erosion and power Doppler (PD) synovitis in 49 patients. In addition, we compared the value of US3 (in which 3 proximal interphalangeal [PIP] and/or metacarpophalangeal [MCP] joints with the highest scores for swelling and tenderness were evaluated) with the 22-joint ultrasound scoring system (US22) in 26 patients. Almost perfect κ coefficients (0.86–0.937) were obtained between AHUS and traditional US in detecting SH, joint effusion, bone erosion and PD synovitis (p < 0.001). The intra-class correlation coefficient (ICC) between AHUS and traditional US was 0.955–0.995. Of the US3 findings in AHUS, SH synovitis and PD synovitis were positively correlated with DAS28-CRP (adjusted R2 = 0.421, p < 0.0001; adjusted R2 = 0.365, p < 0.0001). US3 was highly correlated with US22 in detecting SH and PD synovitis (R = 0.792, p < 0.01; R = 0.948, p < 0.01). Compared with US22, a more significant correlation was identified between US3 scores and most clinical and laboratory values. In conclusion, AHUS performed comparably to traditional US in detecting synovitis in RA, and US3 was highly consistent with US22 in assessing synovitis and was positively correlated with RA disease activity.

Osteoclasts and their circulating precursors in rheumatoid arthritis: Relationships with disease activity and bone erosions

Patients with rheumatoid arthritis (RA) have very different outcomes, particularly with regard to bone erosions. Since osteoclasts are responsible for bone destruction adjacent to rheumatoid synovium, profiling osteoclasts from circulating precursors in RA could help identify patients at risk for bone destruction. In this study, we sought to determine whether the functional characteristics of osteoclasts generated from their blood precursors were modified by RA activity or were intrinsic to osteoclasts and associated with the RA phenotype (erosive or not).Osteoclasts were generated in vitro from peripheral blood mononuclear cells (PBMCs) of subjects with RA (n = 140), as well as sex- and age-matched healthy controls (n = 101). Osteoclastic parameters were analyzed at baseline and during the follow-up for up to 4 years, with regular assessment of RA activity, bone erosions, and bone mineral density (BMD). As a validation cohort, we examined RA patients from the Early Undifferentiated PolyArthritis (EUPA) study (n = 163).The proportion of CD14+ PBMC was higher in RA than in control subjects, but inversely correlated with the 28-joint disease activity score (DAS28). Also surprisingly, in osteoclast cultures from PBMCs, active RA was associated with lower osteoclastogenic capacity, while in vitro bone resorption per osteoclast and resistance to apoptosis were similar in both active and quiescent RA. In a small subgroup analysis, osteoclasts from subjects with recent RA that had progressed at four years to an erosive RA exhibited at baseline greater resistance to apoptosis than those from patients remaining non-erosive.Our findings establish that when RA is active, circulating monocytes have a reduced potential to generate osteoclasts from PBMCs in vitro. In addition, osteoclasts associated with erosive disease had resistance to apoptosis from the start of RA.

Rheumatoid Arthritis Disease Activity Index-5: an easy and effective way of monitoring patients with rheumatoid arthritis

ObjectiveTo study the utility of the Rheumatoid Arthritis Disease Activity Index-5 (RADAI-5) as a valid tool for daily rheumatoid arthritis (RA) monitoring and to compare its predictability to assess RA activity with respect to Disease Activity Score 28 (DAS28) and Clinical Disease Activity Index (CDAI).Patients and methodsA total of 100 patients with RA (diagnosed as per American College of Rheumatology 1987 criteria) were enrolled in the study group. Each patient was assessed two times with 3-month interval for disease activity (DA) using DAS28, CDAI, and RADAI-5. Spearman’s correlation coefficient (p) for correlation and kappa for agreement between different activity measures were assessed.ResultsIn our study group, 19% patients were men and 81% patients were women, with male to female ratio of 1 :4.3. Their mean age was 44.4±11.8 years, and their mean disease duration was 67.5±59.8 months. On initial visit, that is, baseline, mean DA as per RADAI-5, DAS28, and CDAI were 5.14±2.17, 5.58±1.55, and 27.96±15.46, respectively, and on follow-up visit, the readings were 3.76±1.92, 4.54±1.41, and 17.67±12.46, respectively. The mean changes in DA at follow-up visit were -1.37 ±2.15 by RADAI-5, -1.04±1.58 by DAS28, and -10.29±15.75 by CDAI. Changes in DA indices correlated significantly with each other with p ranging from 0.8 to 0.9 (P<0.001). An average agreement was found among all three measures at different DA level.ConclusionRADAI-5 seems to be an effective tool with high tendency to assess the changes in RA DA in routine patient care in hospital settings as well as in home-based settings.

Validity of 7-Joint Versus Simplified 12-Joint Ultrasonography Scoring Systems in Assessment of Rheumatoid Arthritis Activity.

Musculoskeletal ultrasonography (US) is an objective tool for the evaluation of disease activity in rheumatoid arthritis (RA) patients. There is no consensus on the exact number of joints that should be examined. Examination of reduced joint count is more practical than the comprehensive one. This is a cross-sectional study investigated the validity of a 7-joint US score (US7) in assessment of joint inflammation in RA patients compared with a simplified 12-joint US score (US12) and correlated both to composite disease activity indices. The activity status of 50 RA patients was assessed clinically and ultrasonographically. The disease activity was calculated using 3 composite indices. Ultrasonography was performed by 1 blinded rheumatologist, using power Doppler (PD) and gray-scale (GS) US examination. The US7 and simplified US12 were performed as originally described. However, the GS synovitis and PD synovitis of US12 were computed in 2 separate scores instead of 1. Two sum US7 scores were added, sum (GS) US7 and sum (PD) US7 after summating synovitis and tenosynovitis scores. Ultrasonography interobserver/intraobserver reliability was evaluated on 40 stored images. Correlation coefficient between the different ultrasonographic scores showed no difference. The GS scores showed no correlation with disease activity parameters; however, the PD scores did. The sum (PD) US7 was the only score that showed significant correlation with the 3 different composite disease indices. All studied US scores proved valid in assessment of disease activity status in RA. This is in favor of using the less-time-consuming US7 scores. The strongest correlation found with sum (PD) US7 confirmed the importance of incorporating the tendon in the disease activity assessment.

The Use of Interleukin-22 as a Novel Marker of Disease Activity in Female Patients with Rheumatoid Arthritis

Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by progressively destructive joint inflammation and destruction of articular cartilage, bone and synovial hyperplasia. Cytokines play a fundamental role in the processes that cause inflammation, articular destruction and extra-articular manifestations associated with RA.The preferential production of interleukin22 (IL22) by T cells suggests that elevated levels of this cytokine exist in chronic, T cell-mediated diseases, such as psoriasis and RA and that IL-22 plays an important role in the pathogenesis of these disorders. Objective: To study the role of IL-22 in RA. Methods:IL-22 serum levelswere measuredin55 female patients with RA, 28 of them on medical treatment and the other 27 were newly diagnosed patients and in 18 healthy controls. Patients are assessed for clinical and laboratory variables. Correlations of IL-22 serum levels with disease activity markers as disease activity score for 28 joints (DAS28), serological markers, bone erosions were assessed. Results: IL-22 levels were increased in patients with RA compared with controls (mean 34.6 pg/ml and 3.2pg/ml, respectively; P < 0.001). Levels of IL-22 correlated positively with DAS28 score (P <0.001). C-reactive protein (CRP) correlated positivity with high levels of IL-22 in RA patients (mean 53.8 pg/ml; P < 0.001) and rheumatoid factor (RF) correlated positivity with high levels of IL-22 in RA patients (mean 46.1 pg/ml;P < 0.001). The presence of bone erosions was associated with high IL-22 levels (P = 0.008). Conclusion:IL-22 is elevated in the serum of patients with RA.Elevated serum IL-22allows discrimination between patients with different clinical and laboratory measures and indicates thepotential of IL-22 as an additional tool for assessment of activity in RA, particularly in patients with RFantibodies. IL-22 is associated with bone destructive disease.

Risk factors for acute coronary events in patients with rheumatoid arthritis

ObjectivesThe aim of this study was to assess the role of disease activity, line of treatment, and carotid atherosclerosis in the risk for acute coronary syndrome (ACS) in rheumatoid arthritis (RA) patients.Patients and methodsIn this prospective study, we ascertained ACS on 124 patients with RA. Disease activity score 28 was used for the assessment of RA activity. Insulin resistance was evaluated using homeostasis model assessment-insulin resistance. Carotid atherosclerosis was measured using high-resolution ultrasound. We used Cox’s proportional hazards models to estimate the association between ACS and atherosclerosis, cardiovascular (CV) risk factors, and RA line of treatment.ResultsAmong the 124 RA patients without a history of previous ACS, 16 incident ACS events occurred over 30 months. Old age, long RA disease duration, high BMI, and 10-year cardiovascular disease risk were associated with an increased risk for ACS. High mean disease activity score 28, rheumatoid factor, and anticitrullinated peptide antibodies (ACPA) levels were significantly associated with ACS risk. Treatment with disease-modifying antirheumatic drugs or biological disease-modifying antirheumatic drugs (DMARDs) did not alter the ACS risk. Logistic regression analysis showed that carotid plaques were a good predictor for ACS in RA patients.ConclusionThe main finding of this study was a general tendency toward an association of disease activity, rheumatoid factor, and ACPA with the risk for ACS. In addition, subclinical atherosclerosis detected by means of carotid intima-media thickness and the presence of carotid plaques were good predictors for RA patients with ACS. Treatment with any DMARD or biologic DMARDs was not linked to an altered risk for ACS.

Serum Calprotectin in Rheumatoid Arthritis: A Promising Diagnostic Marker, How Far Is It Related to Activity and Sonographic Findings?

BackgroundIn the past 2 decades, there has been increasing interest in calprotectin. It is released and detected in serum and body fluids as a potentially useful clinical inflammatory marker. The protein has been described in synovial tissue in rheumatoid arthritis (RA) patients, specifically in the lining layer adjacent to the cartilage–pannus junction, which is the primary site of cartilage destruction and bone erosion. Assessment of inflammatory activity in RA is of pivotal importance for the optimal treatment. Our aim in this study is to measure the serum calprotectin levels in RA patients and to assess its association—if there is any—with disease activity score and radiological findings using the musculoskeletal ultrasound. Patients and methodsIn our case control study, we included 44 RA patients (Group I) and 20 age- and sex-matched healthy volunteers who served as the control group (Group II). Both groups were subjected to full history taking and thorough clinical examination. Assessment of RA disease activity state was done for all RA patients using the Disease Activity Score 28. Laboratory investigations included the measurement of complete blood cell count, erythrocyte sedimentation rate, C-reactive protein, rheumatoid factor, anticitrullinated peptide antibodies, kidney, liver functions; serum calprotectin levels were determined using enzyme-linked immunosorbent assay and radiological joint assessment was done using musculoskeletal ultrasound score. ResultsThere was a statistically significant elevation of serum calprotectin levels among RA patients when compared with healthy controls. Statistically significant correlations were also found between serum calprotectin and the ultrasound grading score, Disease Activity Score 28, and erythrocyte sedimentation rate, which reflect the degree of inflammatory activity in the affected joints in RA patients. Moreover, the study yielded a significant correlation between serum calprotectin levels and rheumatoid autoantibodies (rheumatoid factor and anticitrullinated peptide antibodies), which are strong predictors of the aggressiveness of the disease. Serum calprotectin at a cutoff level of 93.9 μg/dL had 88.6% sensitivity and 100% specificity for diagnosis of RA. ConclusionCalprotectin was found to have high association with laboratory and ultrasonography markers of inflammation in RA patients, so it is recommended for use as a marker of inflammatory activity in RA patients especially for the follow-up of patients on biological therapy to assess its efficacy.

Association Between Body Composition and Inflammatory Activity in Rheumatoid Arthritis. A Systematic Review

BackgroundReports regarding the association between body composition and inflammatory activity in rheumatoid arthritis (RA) have consistently yielded contradictory results. ObjectiveTo perform a systematic review on the association between overweight/obesity and inflammatory activity in RA. MethodsFAST approach: Article search (Medline, EBSCO, Cochrane Library), followed by abstract retrieval, full text review and blinded assessment of methodological quality for final inclusion. Because of marked heterogeneity in statistical approach and RA activity assessment method, a meta-analysis could not be done. Results are presented as qualitative synthesis. ResultsOne hundred and nineteen reports were found, 16 of them qualified for full text review. Eleven studies (8147 patients; n range: 37–5161) approved the methodological quality filter and were finally included. Interobserver agreement for methodological quality score (ICC: 0.93; 95% CI: 0.82–0.98; P<.001) and inclusion/rejection decision (k 1.00, P>.001) was excellent. In all reports body composition was assessed by BMI; however a marked heterogeneity was found in the method used for RA activity assessment. A significant association between BMI and RA activity was found in 6 reports having larger mean sample size: 1274 (range: 140–5161). On the other hand, this association was not found in 5 studies having lower mean sample size: 100 (range: 7–150). ConclusionsThe modulation of RA clinical status by body fat mass is suggested because a significant association was found between BMI and inflammatory activity in those reports with a trend toward higher statistical power. The relationship between body composition and clinical activity in RA requires be approached with further studies with higher methodological quality.

Identification of novel urinary biomarkers for assessing disease activity and prognosis of rheumatoid arthritis.

To optimize treatment for rheumatoid arthritis (RA), it is ideal to monitor the disease activity on a daily basis because RA activity fluctuates over time. Urine can be collected routinely at home by patients. Recently, we identified four urinary biomarker candidates—gelsolin (GSN), orosomucoid (ORM)1, ORM2 and soluble CD14 (sCD14)—in RA patients through transcriptomic and proteomic studies. Here, we investigated the clinical significance of the aforementioned urinary biomarker candidates in a prospective manner. For the first time, we found that urinary ORM1, ORM2 and sCD14 levels, but not GSN, were elevated in RA patients and had a positive correlation with the status of the disease activity. In particular, urine tests for ORM 1, ORM 2 and sCD14 efficiently represented the presence of high RA activity without the need for measuring blood markers. In a parallel study, a more rapid radiographic progression over 3 years was observed in patients with higher ORM2 levels. Combined measurements of urinary ORM2 and serum C-reactive protein synergistically increased the predictability of the radiographic progression of RA (odds ratio: 46.5). Collectively, our data provide evidence that blood-free, urinary biomarkers are promising surrogates for assessing disease activity and prognosis of RA. We anticipate that our urinary biomarkers will provide novel candidates for patient-driven measurements of RA activity at home and can shift the paradigm from blood to urine testing in the assessment of RA activity and prognosis in hospitals.

The Association Between Neutrophil/Lymphocyte Ratio and Disease Activity in Rheumatoid Arthritis and Ankylosing Spondylitis.

Elevated neutrophil count is associated with poor prognosis and increased mortality in many conditions. Neutrophil to lymphocyte ratio (NLR) has emerged as a marker of inflammation in neoplastic and cardiovascular disorders. Herein, we investigated utility of this simple tool in rheumatoid arthritis (RA) and ankylosing spondylitis (AS). The study consisted of 136 RA and 140 AS patients, along with 117 healthy control subjects. RA and AS activities were determined with Disease Activity Score (DAS) and Bath Ankylosing Spondylitis Disease Activity indices (BASDAI), respectively. The association between NLR and disease activity was analyzed. Erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and neutrophil counts were significantly higher in RA and AS patients compared to healthy controls. Similarly, NLR was higher compared to control subjects, both in RA (2.53 ± 1.4 vs. 2.16 ± 1.0, P = 0.019) and AS (2.43 ± 1.4 vs. 2.16 ± 1.0, P = 0.077). NLR correlated well with ESR and CRP, both in RA and AS. Moreover, NLR increased across worsening DAS28 activity groups (2.1 ± 1.0 in patients with remission, 2.5 ± 1.0 in low-moderate, 3.8 ± 2.5 in high disease activity). However, no association was found between NLR and BASDAI. NLR is a cheap and readily available marker for the assessment of disease activity in RA.

Asociación entre composición corporal y actividad inflamatoria en artritis reumatoide. Una revisión sistemática

BackgroundReports regarding the association between body composition and inflammatory activity in rheumatoid arthritis (RA) have consistently yielded contradictory results. ObjectiveTo perform a systematic review on the association between overweight/obesity and inflammatory activity in RA. MethodsFAST approach: Article search (Medline, EBSCO, Cochrane Library), followed by abstract retrieval, full text review and blinded assessment of methodological quality for final inclusion. Because of marked heterogeneity in statistical approach and RA activity assessment method, a meta-analysis could not be done. Results are presented as qualitative synthesis. ResultsOne hundred and nineteen reports were found, 16 of them qualified for full text review. Eleven studies (8,147 patients; n range: 37-5,161) approved the methodological quality filter and were finally included. Interobserver agreement for methodological quality score (ICC: 0.93; 95% CI: 0.82-0.98; P<.001) and inclusion/rejection decision (k 1.00, P>.001) was excellent. In all reports body composition was assessed by BMI; however a marked heterogeneity was found in the method used for RA activity assessment. A significant association between BMI and RA activity was found in 6 reports having larger mean sample size: 1,274 (range: 140-5,161). On the other hand, this association was not found in 5 studies having lower mean sample size: 100 (range: 7-150). ConclusionsThe modulation of RA clinical status by body fat mass is suggested because a significant association was found between BMI and inflammatory activity in those reports with a trend toward higher statistical power. The relationship between body composition and clinical activity in RA requires be approached with further studies with higher methodological quality.

CHANGES IN CALPROTECTIN LEVEL, ITS RELATIONSHIP TO THE CLINICAL AND LABORATORY PARAMETERS OF DISEASE ACTIVITY AND SIGNIFICANCE FOR PREDICTING THE THERAPEUTIC RESPONSE IN RHEUMATOID ARTHRITIS PATIENTS TREATED WITH ETANERCEPT

Objective: to analyze changes of serum calprotectin (CP) concentration, its relationship to the clinical and laboratory parameters of rheumatoid arthritis (RA) activity, and the significance of baseline CP level for predicting therapeutic response in RA patients treated with etanercept (ETC). Subjects and methods. A total of 84 patients with moderate and high RA activity (mean DAS28 6.35±0.92) who had been ineffectively treated with disease-modifying antirheumatic drugs were examined. The patients received ETC 50 mg/week subcutaneously for 34 weeks. To assess RA activity, tender and swollen joint count, pain, patient’s and physician’s assessment of global disease activity on 100-mm visual analogue scale and DAS28 were used. Functional status was evaluated by HAQ and RAPID3. Treatment efficacy was assessed according to the European League against Rheumatism (EULAR) criteria and the American College of Rheumatology (ACR) criteria. Serum concentration of CP was tested before, 12 and 25 weeks after start of therapy. Results and discussion. There was a statistically significant (p < 0.0001) decrease in CP concentrations after 12 weeks of ETC therapy. Later (after 25 weeks) CP level remained essentially unchanged. CP concentration correlated with erythrocyte sedimentation rate, C-reactive protein level, swollen joint count, and DAS28. Baseline CP level was not a predictor for achieving the therapeutic response according to the EULAR and ACR criteria. In a group of patients unresponsive to treatment according to the EULAR criteria, CP levelrose at 25 weeks whereas it fell during clinical improvement. In the patients achieving ACR 50 and 70% response, changes of CP level were significantly better than those in the other patients. Conclusion. ETC therapy caused a considerable reduction of CP level, clinical and laboratory parameters of RA activity. The baseline concentration of CP was not a predictor for achieving the response to ETC treatment.