Relation of some clinical composite indices of disease activity in rheumatoid arthritis to a simplified 12 joint power Doppler ultrasound activity index

Aim of the workTo assess the association of some clinical composite disease activity indices with a simplified 12 joint power Doppler ultrasound (PDUS) activity index in rheumatoid arthritis (RA).Patients and methodsOne hundred RA patients who fulfilled the 2010 European league against rheumatism/American college of Rheumatology (EULAR/ACR) classification criteria for RA were recruited from the Rheumatology outpatient clinic, Cairo University Hospitals. Disease activity score (DAS28), the simplified disease activity index (SDAI), clinical disease activity index (CDAI) as well as mean overall index for RA (MOI-RA) were assessed. Grey Scale Ultrasonography (GSUS) and PDUS activity assessment was performed using a simplified 12-joint score.ResultsThe 100 patients were 80 females and 20 males (F:M 4:1). Their mean age was 44.4 ± 10.8 years with disease duration of 6.3 ± 4.7 years. Rheumatoid factor was positive in 77 %. DAS28 was 4.5 ± 1.3, SDAI 27.7 ± 22.7, CDAI 17.5 ± 13.2 and MOI-RA 86.8 ± 25.1. On US, tenosynovitis was present in 10 %, irregularity in 23 % and erosion in 62 %. The mean 12-point PDUS was 3.53 ± 4.16 and the overall US score 10.34 ± 9.3. A significant correlation was found between the US findings of overall synovitis, degree of PD and US score with DAS28 (r = 0.3, p < 0.0001; r = 0.4, p < 0.0001 and r = 0.3, p < 0.0001) with SDAI (r = 0.3, p < 0.0001; r = 0.4,p < 0.0001; r = 0.4, p < 0.0001) and with MOI-RA score (r = 0.3, p < 0.0001; r = 0.4, p < 0.0001 and r = 0.4, p < 0.0001 respectively) but the highest correlations was with CDAI (r = 0.4, p < 0.0001; r = 0.5, p < 0.0001 and r = 0.4, p < 0.0001 respectively).ConclusionSimplified 12 -joint PDUS score is well correlated with activity indices in RA patients.     

The role of musculoskeletal ultrasound in assessment of disease activity in rheumatoid arthritis patients with fibromyalgia

IntroductionFibromyalgia (FM) is frequently present in rheumatoid arthritis (RA) patients and this can lead to an overestimation of disease activity and consequently overtreatment. Musculoskeletal ultrasound (MSUS) can aid in evaluating synovitis for assessment of disease activity with more precision.Aim of the workTo verify the potential role of MSUS in the assessment of disease activity in RA patients with and without FM.Patients and methodsThis study was conducted on 100 active RA patients. Disease activity score (DAS28) and clinical disease activity index (CDAI) were assessed. MSUS was assessed using the 12 joint simplified score.ResultsThe 100 patients were 88 females and 12 male (F:M 7.3:1) with a mean age of 44.82 ± 11.4 years and disease duration of 6.88 ± 5.77 years. 67 RA patients had associated secondary FM and 33 did not. DAS-28 and CDAI were significantly higher in those with FM (4.99 ± 0.82 and 30.49 ± 10.59) compared to those without (4.22 ± 0.96 and 18 ± 10.68)(p < 0.001). Regarding ultrasonographic finding, no significant difference was found between those with and without FMS. DAS28 and CDAI significantly correlated (p = 0.006, p = 0.002 respectively) with grey scale ultrasound (GS-US12) in patients without FMS while DAS28 only significantly correlated with GS-US12 in those with FMS (r = 0.28, p = 0.022).ConclusionSecondary FM is common in RA patients and associated with a higher disease activity making it a potential influencer on the treatment strategy. MSUS can complement physical examination in the assessment of disease activity but had a limited role to delineate RA patients with FM from those without.     

Comparative validation of clinical disease activity index (CDAI) and simplified disease activity index (SDAI) in rheumatoid arthritis in India

BackgroundCDAI and SDAI have been frequently used to categorize disease activity in patients with rheumatoid arthritis (RA), but have not been comparatively validated in Indian population.ObjectiveTo validate CDAI and SDAI in RA, taking DAS-28 as gold standard and to derive new cutoffs for CDAI and SDAI.MethodsPatients fulfilling ACR/EULAR criteria for diagnosis of RA were studied. After complete history, physical examination and biochemical tests, patients were grouped into remission, low, moderate and high activity on the basis of pre-defined cut-offs for DAS-28, CDAI, and SDAI. Spearman’s correlation and group wise inter-rater agreement tests were performed. Using DAS-28 as gold standard, the sensitivity and specificity of CDAI and SDAI cut off were determined for predicting levels of disease activity by area under receiver operator characteristics curves. (AUROC)ResultsWe studied 112 patients with RA, there was excellent correlation between DAS-28 and CDAI (r = 0.96 with 95% C.I. = 0.94?0.97), CDAI and SDAI (r=0.99, 95% C.I. 0.98?1), and DAS-28 and SDAI (r = 0.96, 95% C.I. = 0.94?0.97). There was a good inter-rater agreement between the various levels of disease activity as defined by DAS-28 and CDAI (weighed k = 0.598) and DAS-28 and SDAI (weighed k = 0.699) with excellent agreement between SDAI and CDAI categories (weighed k = 0.816). There was no statistically significant difference between AUROC of CDAI and SDAI and both performed equally well.ConclusionCDAI and SDAI are highly correlated with DAS-28 score hence are good markers of disease activity. The cut-off values for CDAI and SDAI used in western literature can be used with minor modifications in Indian scenario.     

Comparison of composite disease activity indices for rheumatoid arthritis

To evaluate the composite disease activity indices for rheumatoid arthritis (RA), we compared disease activities and the changes therein calculated using the Disease Activity Score based on 28 joint counts using erythrocyte sedimentation rate (DAS28-ESR), DAS28-CRP (C-reactive protein), Simplified Disease Activity Index (SDAI), and Clinical Disease Activity Index (CDAI) in a cohort of 1,412 patients with RA. The median (1st; 3rd quartile) scores were 4.20 (3.31; 5.14) for DAS28-ESR, 3.44 (2.59; 4.36) for DAS28-CRP, 13.6 (7.49; 21.1) for SDAI, and 12.0 (6.9; 18.9) for CDAI. Absolute scores and their changes were significantly correlated (p < 0.0001) in all combinations among these four disease activity indices; however, their correlations were lower in males than in females. Correlations between disease activity indices and the clinical and acute phase reactant variables were different according to disease activity index, sex and age. A comparison of the number of patients in each disease activity category according to the disease activity indices using kappa-statistics revealed an almost perfect agreement between SDAI and CDAI (κ = 0.871), a moderate agreement between DAS28-ESR and SDAI (κ = 0.415) or CDAI (κ = 0.427), but only fair agreement between DAS28-ESR and DAS28-CRP (κ = 0.329). For the selection of a disease activity index for an evaluation of RA patients, both the convenience and the characteristics of the respective disease activity index should be considered.     

Visualization of DAS28, SDAI,and CDAI: the magic carpets of rheumatoid arthritis

There has been continuous debate regarding the applicability of various composite measures for the assessment of disease activity in rheumatoid arthritis (RA). In order to further dissect this issue, we numerically and graphically modeled 28-joint disease activity scale (DAS28), simplified disease activity index (SDAI), and clinical disease activity index (CDAI) by three-dimensional (3D) plotting. We wished to graphically visualize the relative contribution of various elements in the three activity indices to each other. We calculated DAS28 (3 variables), SDAI, and CDAI by the standard equations. We plotted 3D “carpets” showing all combinations of the corresponding variables yielding to DAS28?=?5.1, DAS28?=?3.2, DAS28?=?2.6, SDAI?=?26, SDAI?=?11, and SDAI?=?3.3. We also plotted the 3D carpet for CDAI. In patients with high or moderate disease activity, erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP) was not a major confounding factor when calculating DAS28 and SDAI, respectively. In contrast, ESR and CRP highly overshadowed changes in joint counts and global assessments in patients with low disease activity (LDA) or those in remission. No reliable assessment of LDA can be performed in cases where ESR >54 mm/h or CRP >20 mg/dl. Similarly, remission cannot be determined if ESR >19 mm/h or CRP >5 mg/dl. As CDAI does not include acute phase reactants, CDAI may be a useful tool even in states of remission or LDA. Our results suggest that acute phase reactants are indeed major confounding factors and should be omitted when assessing RA disease activity at least in special cases.     

Gastroesophageal reflux disease in patients with rheumatoid arthritis

Abstract

Objective. Patients with rheumatoid arthritis (RA) are frequently complicated with gastric mucosal injury; however, there are few reports investigating gastroesophageal reflux disease (GERD) among patients with RA. We investigated the frequency of GERD and the correlation between GERD and the clinical characteristics of RA including patient's global assessment (PGA).

Methods. Patients with RA were investigated for GERD using self-administered frequency scale for the symptoms of GERD (FSSG). The correlation between GERD and the clinical characteristics of RA was analyzed statistically.

Results. Two hundred and eleven patients in Japan were investigated. The prevalence of GERD among patients with RA (24.6%) was significantly higher than that in the Japanese population (11.5%) (p < 0.001). FSSG was positively correlated with modified health assessment questionnaire (mHAQ), PGA, evaluator's global assessment (EGA) (p < 0.001), disease activity score (DAS)28-erythrocyte sedimentation rate (ESR) (p < 0.05), DAS28-C-reactive protein (CRP), simplified disease activity index (SDAI) and clinical disease activity index (CDAI) (p < 0.001). The patients with GERD showed significantly higher scores in mHAQ, PGA, EGA, tenderness joint count, DAS28-ESR, DAS28-CRP, SDAI and CDAI (p < 0.001). Furthermore, the patients with GERD showed lower remission rates based on DAS28-ESR (p < 0.05), DAS28-CRP, SDAI and CDAI (p < 0.001).

Conclusion. GERD complicated with RA increases PGA and the indices of disease activity. GERD symptoms analyzed using FSSG may be desirable to avoid the overestimation as part of the total management of patients with RA.     

Evaluation of disease activity indices in Korean patients with rheumatoid arthritis

The aim of this study is to examine the validity of the rheumatoid arthritis (RA), disease activity score (DAS), 28-C-reactive protein (CRP), the simplified disease activity index (SDAI), and the clinical disease activity index (CDAI) against the DAS28-erythrocyte sedimentation rate (ESR) and determine cut-off values for each tool in Korean patients with RA. A total of 223 RA patients were consecutively recruited from the Hanyang University Hospital for Rheumatic Diseases in Seoul, Korea. DAS28-CRP, SDAI, and CDAI were measured and compared with DAS28-ESR. The correlation coefficients of DAS28-ESR with DAS28-CRP, SDAI, and CDAI were 0.93, 0.85, and 0.84, demonstrating strong linear relationships. The cut-off values of DAS28-CRP classifying RA patients into four categories of disease activity were defined as 2.19, 2.60, and 4.07. SDAI cut-off values were defined as 3.75, 7.50, and 16.88. CDAI cut-off values were defined as 3.62, 7.38, and 16.50. DAS28-CRP, SDAI, and CDAI are valid and sensitive assessment indices of disease activity that are comparable to DAS28-ESR. The cut-off values of each tool derived in this study might be useful for routine monitoring and therapeutic decision-making in Korean RA patients.     

Serum and synovial fluid interleukin-17 concentrations in rheumatoid arthritis patients: Relation to disease activity,radiographic severity and power Doppler ultrasound

Aim of the workTo investigate serum and synovial fluid levels of IL-17 in rheumatoid arthritis (RA) patients, and its correlation with disease activity and severity.Patients and methods20 RA patients together with 20 primary knee osteoarthritis (KOA) patients and 15 healthy individuals matched for age and sex as control groups were enrolled in this study. Both RA and KOA patients presented with knee effusion. Paired samples of serum and synovial fluid (SF) were collected from RA, OA patients and serum samples from the healthy individuals. RA disease activity was assessed using DAS-28 score and power Doppler ultrasound (PDUS) according to the European League against Rheumatism (EULAR). Radiographic damage was evaluated according to Larsen score.ResultsSerum levels of IL-17 were significantly elevated in RA patients compared to controls (p < 0.001). Also, SF of IL-17 was significantly higher in RA patients compared to OA patients (p < 0.001). In addition, synovial level of IL-17 was significantly higher in RA patient compared to their serum level (p < 0.001). Regarding disease activity grading among RA patients, significant differences (p < 0.05) in mean serum and synovial IL-17 levels were reported being higher in severe active disease. Positive correlations of serum and SF IL 17 levels with PDUS findings and Larsen score were reported.ConclusionSerum and synovial IL-17 levels were significantly elevated in RA patients which clarifies its possible role in RA pathogenesis and correlates positively with disease activity parameters, PDUS findings and Larsen score. Thus targeting IL-17 may provide a promising role in suppressing RA.     

Comparative assessment of hepatitis C virus-related arthritis and rheumatoid arthritis: Relation to clinical,serologic and ultrasonographic characteristics

BackgroundExtrahepatic manifestations of hepatitis C virus (HCV) infection includes HCV-related arthritis (HCV-A) that may mimic rheumatoid arthritis (RA). Musculoskeletal ultrasound (MSUS) can aid in discriminating both conditions.Aim of the workTo study the clinical, serological and imaging (Xray, MSUS) characteristics of HCV-A and compare them to RA.Patients and methodsThe study included 30 patients with HCV-A and 30 age- and sex-matched RA patients negative for HCV. Ritchie articular index (RAI), tender joint count (TJC) and swollen joint count (SJC) assessed arthritis. Patient global health assessment (PGHA) and modified health assessment questionnaire (MHAQ) were evaluated. The erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), rheumatoid factor (RF), anti-cyclic citrullinated peptide (anti-CCP) and serum cryoglobulins were measured. Radiologic assessment included short Larsen score (SLS) and MSUS using 7-joint ultrasound score (US7).ResultsThe mean age of the HCV-A patients was 45.8 ± 4.7 years; RA was 43.3 ± 5.6 years; F:M was 27:3 in HCV-A patients; 29:1 in RA; HCV-A patients had no subcutaneous nodules, joint deformities or bone erosions. US7 showed that Gray-Scale (GS)/Power Doppler (PD) synovitis and tenosynovitis had higher mean values in RA versus HCV-A patients (p < 0.001; p < 0.001; p = 0.011; p = 0.008 respectively). A significant correlation was found between SJC with GS and PD synovitis in both groups.ConclusionHCV-A differ from RA features as being non nodular, non-deforming, non-erosive and aid in the predilection of HCV-A diagnosis. MSUS can offer a useful imaging modality elucidating inflammatory components of HCV-A and highlighting the spectrum of the condition.     

Revising DAS28 scores for remission in rheumatoid arthritis

Current initiatives to treat rheumatoid arthritis (RA) to target remission have resulted in the widespread use of composite outcome measures to quantify disease activity. Simplified Disease Activity Index (SDAI) ≤3.3 is the gold standard of remission. Previous work has suggested that the remission threshold of DAS28-ESR or DAS28-CRP ≤2.6 is known to be not strict enough and should be revised. There is no previous study that looks at the equivalent DAS28-CRP value that best reflects SDAI remission in a real-life cohort. Consecutive cases fulfilling ACR/EULAR classification criteria for RA from one centre were included if they had an optimum number of visits with recording of all raw data to calculate DAS28-ESR, DAS28-CRP and SDAI. Data from seven visits each of 76 patients, providing 532 data points was examined. Spearman’s correlation between DAS28-ESR, DAS28-CRP and SDAI was 0.91–0.97 (p?<?0.001). A Bland-Altman plot demonstrated a mean difference of 0.37 units between DAS28-ESR and DAS28-CRP (p?<?0.001). ROC and kappa analysis provided values of 2.58 and 2.55 for DAS28-ESR4V and 2.09 and 2.05 for DAS28-CRP4V for SDAI value of 3.3, respectively. The two versions of DAS28 using ESR and CRP and SDAI correlate but are not equivalent or interchangeable for an individual patient. The DAS28-CRP overestimates remission and should be revised downwards to a proposed value of 2.1.     

Which subgroup of rheumatoid arthritis patients benefits from switching to tocilizumab versus etanercept after previous infliximab failure? A retrospective study

A retrospective study of 39 rheumatoid arthritis (RA) patients with an inadequate response to infliximab was conducted. The responses of subjects switching from infliximab to tocilizumab (n = 23) were compared to those of subjects switching to etanercept (n = 16). Disease activity was assessed by the Disease Activity Score 28-CRP ([C-reactive protein] DAS28-CRP), the Simplified Disease Activity Index (SDAI), and the Clinical Disease Activity Index (CDAI). Twenty-two patients completed 48 weeks of tocilizumab treatment, and 15 patients completed 48 weeks of etanercept treatment. In both treatment groups, 1 patient each discontinued treatment because of lack of efficacy. No serious adverse events occurred during the study, and no patients in either group withdrew due to adverse events. At week 48, there was a significant reduction from baseline in DAS28-CRP, SDAI, and CDAI values after switching to either tocilizumab or etanercept, and there was no significant difference in efficacy, as measured by the DAS28-CRP, SDAI, and CDAI, between the two treatment groups (p = 0.12, 0.76, and 0.86, respectively). These results suggest that safety and tolerability were similar for both treatments. A switch from infliximab to either tocilizumab or etanercept in patients with RA who have not responded to infliximab is a feasible, well-tolerated treatment option.     

Assessment of the validity of the 28-joint disease activity score using erythrocyte sedimentation rate (DAS28-ESR) as a disease activity index of rheumatoid arthritis in the efficacy evaluation of 24-week treatment with tocilizumab: subanalysis of the SATORI study

As tocilizumab (TCZ) greatly inhibits inflammatory markers, methods of evaluating rheumatoid arthritis (RA) disease activity that include inflammatory markers may overestimate the effect of TCZ treatment. We have evaluated the impact of inflammatory markers on the efficacy of TCZ by comparing the efficacy indicated by the 28-joint disease activity score using erythrocyte sedimentation rate (DAS28-ESR) with that indicated by the clinical and simplified disease activity indexes (CDAI and SDAI, respectively) and the American College of Rheumatology (ACR) core set criteria in a double-blind study of TCZ—the SATORI study. The Spearman correlation coefficient between DAS28-ESR and CDAI was comparable between that at week 24 and that at baseline [correlation coefficient at baseline and week 24 was 0.823 (p < 0.0001) and 0.818 (p < 0.0001), respectively]. A large difference between the DAS28 remission rate and CDAI remission rate was observed at week 24. However, these results are comparable to those of a previous study conducted with non-TCZ-treated patients. Moreover, the same results were obtained in the comparison between the DAS28-ESR and SDAI, even though the SDAI includes an inflammatory parameter as a component. These results confirm that the DAS28-ESR has a validity comparable to that of other methods in terms of evaluating the RA treatment efficacy of TCZ, despite its strong inflammatory marker-inhibiting effects.     

Clinical Advantage of Attaining Index-Based Remission Prior to Composite Remission in Treating Rheumatoid Arthritis

Background and objectivesThe clinical advantage of targeting index-based remission prior to Boolean remission was evaluated retrospectively.Materials and methodsA total of 578 patients with rheumatoid arthritis (RA), who were treated for more than three years, were recruited. Patients who were treated to targeted index-based remission and composite measure remission criteria such as Boolean remission from the first consultation were divided according to the turn of attaining Boolean remission and index-based remission: G-IBR, a group that matched index-based remission at the same time Boolean remission is attained or earlier; G-BR_IF, a group that attained Boolean remission followed by index-based remission or failed; G-IR_BF, a group that could not attain Boolean remission despite attaining index-based remission; G-BothF, a group that failed to attain either Boolean remission or index-based remission. Background factors were statistically compared among groups. The Boolean remission rate in patients who attained index-based remission (BRR) and the rate of failure to attain index-based remission in patients who failed to attain Boolean remission (BFR) were statistically evaluated.ResultsGroups comprising 225, 231, and 482 in G-IBR; 160, 154, and 8 in G-BR_IF; 18, 18, and 75 in G-IR_BF; and 175, 175, and 13 in G-BothF when indexing the clinical disease activity index (CDAI), simplified disease activity index (SDAI), and 28-joints disease activity score with C-reactive protein (DAS28-CRP), respectively. Disease activity indices’ scores after Boolean remission were demonstrated to be significantly higher in the G-BR_IF group than in the G-IBR group. BRR was 92.6%, 92.8%, and 86.5%, while BFR was 71.3%, 71.3%, and 13.8% when indexing CDAI, SDAI, and DAS28-CRP, respectively.ConclusionsTargeting CDAI and SDAI remission prior to Boolean remission contributes to a stable clinical course.     

Collagen triple-helix repeat containing 1 (CTHRC1) protein in rheumatoid arthritis patients: Relation to disease clinical,radiographic and ultrasound scores

Aim of the workto study the relationship between collagen triple helix repeat containing 1 (CTHRC1) protein serum levels and disease activity, patients’ well-being, as well as ultrasonographic and radiological scores in patients with rheumatoid arthritis (RA).Patients and methodsThe work included 70 RA patients and 70 age and gender matched controls. The disease activity score (DAS28) and health assessment questionnaire (HAQ) were assessed. Modified Larsen's score was used to score the hands and feet digital radiographs and musculoskeletal ultrasound (MSUS) examination using ultrasound-7 score was carried out. Serum CTHRC1 levels were measured by ELISA.ResultsPatients were 62 females and 8 males (F: M 7.8:1), their mean age was 42.2 ± 17.7 years and median disease duration 15 years. The median CTHRC1 serum levels were significantly higher in patients (453 ng/dl; 158–688 ng/dl) than control (99 ng/dl; 67–179 ng/dl) (p < 0.001). CTHRC1 was significantly increased in those with high activity (p < 0.001).CTHRC1 levels significantly correlated with DAS28 (r = 0.87,p < 0.001), CRP (r = 0.43,p < 0.001) and total ultrasound-7 score (r = 0.27,p = 0.03). Only total US7 score (p = 0.003) and CTHRC1 (p < 0.001) were significant predictors of activity. Serum CTHRC1 could significantly differentiate between patients and controls at cut off 179 ng/ml; sensitivity 95.7 % and specificity 100 % (p < 0.001) and between patients active and in remission at cut off 324 ng/ml; sensitivity 92.2 % and specificity 94.7 % (p < 0.001).ConclusionsPatients with RA have significantly elevated serum levels of CTHRC1. In the process of structural bone ultrasonographic abnormalities as well as disease activity in RA patients, elevated CTHRC1 levels play a key role.     

Assessment of serum interleukin-20 level in rheumatoid arthritis patients: Relation to disease activity and ultrasound measures

Aim of the workTo investigate the serum interleukin-20 (IL-20) level in rheumatoid arthritis (RA) patients and to elucidate its relationship with disease activity and ultrasonographic (US) findings.Patients and methods45 RA patients and 45 matched controls were enrolled. Modified health assessment questionnaire (mHAQ) and disease activity score (DAS-28) were determined. Power Doppler (PD) and Gray-scale (GS) US evaluation was made using German US7 score. Serum IL-20 level was analyzed using an enzyme-linked immunosorbent assay.ResultsMean age of patients was 34.5 ± 11 years; 39 females and 6 males and disease duration 15.8 ± 8.3 years. Their mean DAS-28 was 4.1 ± 1.1. The serum IL-20 levels were highly significant in patients (30.2; 19.1–58.5 ng/l) than in controls 13.1; 11–15.1 ng/l; p < 0.001). Serum IL-20 significantly correlated with DAS-28 (r = 0.32, p = 0.03), mHAQ (r = 0.87, p < 0.001), erythrocyte sedimentation rate (r = 0.82, p < 0.001), C-reactive protein (r = 0.32, p = 0.03), and disease duration (r = 0.87, p < 0.001). Significant correlations were found between IL-20 level and German US7 variables including synovitis (PD: p = 0.02 and GS: p = 0.01), tenosynovitis (PD: p = 0.01 and GS: p = 0.01) and erosion (p = 0.02) scores. Only morning stiffness, tenosynovitis GS score, tender joint count and mHAQ were significant predictors of IL- 20 serum level (p = 0.045, p = 0.04, p = 0.03 and p = 0.001 respectively). Serum IL-20 at cut-off point of 15.4 ng/l could significantly distinguish patients from controls (AUC = 0.89; sensitivity 82.2%, specificity 77.8% and accuracy of 80%; p < 0.001).ConclusionPatients with RA exhibited a significant elevation in IL-20. Serum IL-20 level significantly correlated with disease activity and ultrasound variables and may serve as a potentially effective biomarker in the evaluation of disease activity in RA.     

Assessment of the validity of the 28-joint disease activity score using erythrocyte sedimentation rate (DAS28-ESR) as a disease activity index of rheumatoid arthritis in the efficacy evaluation of 24-week treatment with tocilizumab: subanalysis of the SATORI study

Abstract

As tocilizumab (TCZ) greatly inhibits inflammatory markers, methods of evaluating rheumatoid arthritis (RA) disease activity that include inflammatory markers may overestimate the effect of TCZ treatment. We have evaluated the impact of inflammatory markers on the efficacy of TCZ by comparing the efficacy indicated by the 28-joint disease activity score using erythrocyte sedimentation rate (DAS28-ESR) with that indicated by the clinical and simplified disease activity indexes (CDAI and SDAI, respectively) and the American College of Rheumatology (ACR) core set criteria in a double-blind study of TCZ—the SATORI study. The Spearman correlation coefficient between DAS28-ESR and CDAI was comparable between that at week 24 and that at baseline [correlation coefficient at baseline and week 24 was 0.823 (p < 0.0001) and 0.818 (p < 0.0001), respectively]. A large difference between the DAS28 remission rate and CDAI remission rate was observed at week 24. However, these results are comparable to those of a previous study conducted with non-TCZ-treated patients. Moreover, the same results were obtained in the comparison between the DAS28-ESR and SDAI, even though the SDAI includes an inflammatory parameter as a component. These results confirm that the DAS28-ESR has a validity comparable to that of other methods in terms of evaluating the RA treatment efficacy of TCZ, despite its strong inflammatory marker-inhibiting effects.     

Allogeneic mesenchymal stem cells transplantation in patients with refractory RA

This study aimed to determine the safety and efficacy of allogeneic mesenchymal stem cells transplantation (MSCT) in refractory rheumatoid arthritis (RA). Four patients with persistently active RA underwent MSCT. The outcome was evaluated by changes in the visual analog scale (VAS 100 mm) pain score, C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR), and 28-joint disease activity score (DAS-28). Three of four patients received a reduction in ESR, DAS-28, and pain VAS score at 1 and 6 months after transplantation. Two of the three had a European League Against Rheumatism (EULAR) moderate response at 6 months but experienced a relapse at 7 and 23 months, respectively. Two patients had no EULAR response to MSCT. No one had achieved the DAS-28-defined remission in the follow-up period. No serious adverse events were reported. Allogeneic MSCT is a safe treatment in severe and resistant RA, but the effectiveness needs to be clarified.     

Reexamination of the assessment criteria for rheumatoid arthritis disease activity based on comparison of the Disease Activity Score 28 with other simpler assessment methods

Objective

To explore simpler and possibly more appropriate tools than the conventional Disease Activity Score 28 (DAS28) for assessing rheumatoid arthritis (RA) and to derive more reliable DAS28-based criteria.

Methods

The capabilities of assessing disease activities in 250 RA patients were compared between DAS28 and other methods, including the Simplified DA Index (SDAI), Clinical DA Index (CDAI), and Routine Assessment of Patient Index Data-3 (RAPID-3).

Results

SDAI and CDAI showed a good correlation and consistency with DAS28, whereas RAPID-3 yielded inferior results. In terms of remission criteria, DAS28 was less stringent than SDAI or CDAI; when RA remission was reexamined based on more stringent SDAI or CDAI criteria, cut-off values for DAS28-C-reactive protein of <1.72 were considered to be appropriate. The conventional DAS28 was considered to be appropriate for assessing low, middle and high disease activities because it provides criteria similar to or more stringent than those of other methods, while SDAI and CDAI were considered to be simpler and more appropriate criteria for assessing remission.

Conclusion

For assessing remission, DAS28-CRP provides the most appropriate criterion of the methods compared when the currently used cut-off value of 2.3 is lowered to a new value of 1.72.     

Significance of vascular endothelial growth factor (VEGFA)-1154 G/A gene polymorphism (rs1570360) in rheumatoid arthritis patients

Aim of the workTo evaluate the association of the vascular endothelial growth factor (VEGF) 1154G/A single nucleotide polymorphism (SNP) with the risk of RA and its possible relation to different disease parameters.Patients and methodsFifty RA patients and 50 matched healthy controls were enrolled in the study. Disease activity score (DAS28) was assessed. VEGF 1154G/A was measured byreal time polymerized chain reaction (RT-PCR) for patients and controls.ResultsThe patients mean age was 44.2 ± 12.1 years (25–64 years) and they were 41 females and 9 males with a disease duration of 5 ± 3.6 years and DAS28 of 5.88 ± 1.06. None of the patients were in remission or had low disease activity. The VEGF-1154 AA genotype and A allele were significantly higher in controls (54%, 56%) compared to the patients (10%, 23%)(p < 0.001). The GG, GA genotypes and G allele tended to be higher in patients (64%, 26% and 77%) compared to the control (42%, 4% and 44% respectively (p < 0.001). As regards anti-cyclic citrullinated peptide (anti-CCP) and rheumatoid factor (RF), AA genotype was significantly higher in seronegative (93.1% and 96.5%) patients compared to seropositive (6.9% and 3.5%; p = 0.002 and p = 0.005 respectively). There was no significant difference in the genotype according to gender (p = 0.45) or DAS28 (p = 0.78). No significant association was found between the SNP with the age (p = 0.48), disease duration (p = 0.58), ESR (p = 0.97) and CRP (p = 1).ConclusionsThe minor A allele of VEGFA1154G/A might act as a protective factor against RA and might also be related to a better disease prognosis.     

Test–retest reliability of the Disease Activity Score 28 CRP (DAS28-CRP), the Simplified Disease Activity Index (SDAI) and the Clinical Disease Activity Index (CDAI) in rheumatoid arthritis when based on patient self-assessment of tender and swollen joints

Composite disease activity scores are frequently used in daily practice as tools for treatment decisions in patients with rheumatoid arthritis (RA). If reliable, patient-reported disease activity may be time saving in the busy clinic. The objective was to examine the test–retest reliability of the Disease Activity Score 28 CRP (DAS28-CRP) with four variables (4v) and three variables (3v), the Simplified Disease Activity Index (SDAI) and the Clinical Disease Activity Index (CDAI) when based on patient self-assessment of tender and swollen joints and to examine the agreement between these scores and physician-derived scores. Thirty out-clinic RA patients with stable disease were included. A joint count was performed two times 1 week apart by the patient and by an experienced physician. Test–retest reliability was expressed as the least significant difference (LSD), as the LSD in percent of the mean score (%LSD) and as intra-individual coefficients of variation (CV_i). Mean scores based on physician vs. patient joint counts (visit 1) were: DAS28-CRP(4v) 3.5?±?1.0 vs. 3.6?±?1.1 (not significant (NS)), DAS28-CRP(3v) 3.4?±?0.9 vs. 3.5?±?0.9 (NS), SDAI 14.2?±?9.4 vs.14.1?±?9.4 (NS) and CDAI 13.4?±?9.3 vs. 13.3?±?9.4 (NS). The LSDs (%LSD) for duplicate assessments of patient-derived scores (visit 2 vs. 1) were: DAS28-CRP(4v) 0.8 (23.2), DAS28-CRP(3v) 0.9 (25.2), SDAI 8.3 (59.9) and CDAI 8.4 (63.8). Similar LSDs were found for differences between duplicate assessments of physician-derived scores and for differences between physician and patient-derived scores. CV_is for SDAI and CDAI were significantly higher than for DAS28-CRP(4v) and DAS28-CRP(3v) (p?<?0.005). Patient- and physician-derived scores agreed closely on group level. On the individual level, the LSDs between patient- and physician-derived scores were considerable but corresponded to both patient and physician intra-observer LSDs. Thus, scores based on patient-performed joint counts may be an alternative to traditional physician-derived scores in patients with stable disease.