scholarly journals Circulating Semaphorin 4D as a Marker for Predicting Radiographic Progression in Patients with Rheumatoid Arthritis

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
You-Jung Ha ◽  
Dong Woo Han ◽  
Ji Hyoun Kim ◽  
Sang Wan Chung ◽  
Eun Ha Kang ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Radiographic Progression ◽  
Joint Damage ◽  
Multivariate Logistic Regression Analysis ◽  
Serum Levels ◽  
Joint Disease ◽  
Semaphorin 4D ◽  
Reactive Protein ◽  
Baseline Levels

Semaphorin 3A (Sema3A) and semaphorin 4D (Sema4D) are molecules which regulate immune responses as well as bone remodeling process. The aim of this study was to evaluate the serum levels of Sema3A and Sema4D and to investigate their clinical significance in rheumatoid arthritis (RA). The serum levels of Sema3A and Sema4D were measured in 130 patients with RA and 65 sex- and age-matched healthy individuals. Circulating levels of biomarkers of RA-related inflammation and bone turnover such as tumor necrosis factor- (TNF-) α, interleukin- (IL-) 6, IL-22, IL-34, osteopontin, Dkk-1, and sclerostin were also measured. Disease activity was determined by the 28-joint disease activity score (DAS28), and radiographic joint damage was assessed by the modified Sharp van der Heijde score (SHS). The serum levels of Sema3A were significantly higher in patients with RA than those in healthy controls (p<0.001), whereas serum4D levels did not differ between the two groups. The levels of Sema4D showed a positive correlation with C-reactive protein (p=0.001) and IL-6 (p<0.001) levels, whereas the levels of Sema3A showed a negative correlation with Dkk-1 (p=0.007) and TNF-α (p=0.001). Even though Sema3A and Sema4D levels were comparable between RA patients with DAS28> 3.2 and with DAS28 ≤ 3.2, RA patients with radiographic progression (ΔSHS change/year ≥ 1) had significantly higher baseline levels of Sema4D than those without progression (p=0.029). Additionally, when RA patients were divided into 3 groups using tertiles of Sema4D levels, the percentage of progressors was significantly increased (p=0.045). In multivariate logistic regression analysis, serum Sema4D levels were an independent risk factor for radiographic progression. Our results suggest that the baseline levels of Sema4D might be a useful marker to identify RA patients with subsequent radiographic progression and that Sema4D may be an active mediator involved in RA-induced joint damage.

scholarly journals Anticitrullinated Protein Antibody, But Not Its Titer, Is a Predictor of Radiographic Progression and Disease Activity in Rheumatoid Arthritis

2012 ◽  
Vol 39 (4) ◽  
pp. 694-700 ◽  
Author(s):  
KAZUKO SHIOZAWA ◽  
YOSHIKO KAWASAKI ◽  
TAKASHI YAMANE ◽  
RYOSUKE YOSHIHARA ◽  
YASUSHI TANAKA ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Radiographic Progression ◽  
Disease Onset ◽  
Joint Disease ◽  
Reactive Protein ◽  
Patient Groups ◽  
The Relationship ◽  
Positive Groups ◽  
Extent Of Disease

Objective.To study the contribution of anticitrullinated protein antibody (ACPA), and especially of its titer, to radiographic progression and disease activity in rheumatoid arthritis (RA).Methods.Patients with RA (n = 396) who attended a Japanese clinic within 2 years after disease onset were divided into the following groups according to second-generation (ACPA-2) ACPA titer on their first visit: negative (0–4.4 U/ml; n = 115), low-positive (4.5–121 U/ml; n = 141), and high-positive (> 121 U/ml; n = 140). The ACPA-2-positive groups were further subdivided into lowest (4.5–32 U/ml), low (33–121 U/ml), high (122–277 U/ml), and highest (> 278 U/ml) quartiles. All patients were treated with disease-modifying antirheumatic drugs (DMARD) including methotrexate, but not biologics. Subsequent radiographic progression and disease activity for 2 years were prospectively evaluated using the van der Heijde-modified Sharp score (SHS) and 28-joint Disease Activity Score (DAS28).Results.After treatment with DMARD, the disease activity (including number of swollen joints, number of tender joints, duration of morning stiffness, DAS28-erythrocyte sedimentation rate, and DAS28-C-reactive protein) was significantly decreased in all patient groups. Disease activity and radiographic progression as revealed by the change in SHS remained relatively higher in the ACPA-2 low- and high-positive groups as compared with the ACPA-2-negative group. The relationship between the titer of ACPA-2 at baseline and subsequent radiographic progression was not exactly linear, and the extent of disease activity or radiographic progression was similar between ACPA-2 low- and high-positive groups and also between ACPA-2 lowest- and highest-positive quartile groups. The results were demonstrable in cumulative SHS probability plots, and also repeatable in seronegative patients, which indicated that the titer of ACPA-2 is not a predictor of disease activity or radiographic progression in RA, and ACPA-2-negative patients, especially those with < 3 U/ml, showed minimal radiographic progression.Conclusion.Presence of ACPA-2, but not its titer, at baseline is a predictor of radiographic progression or disease activity, where radiographic progression is minimal in ACPA-2-negative patients.

Inflammation and Disease Activity are Associated with High Circulating Cardiac Markers in Rheumatoid Arthritis Independently of Traditional Cardiovascular Risk Factors

2013 ◽  
Vol 41 (2) ◽  
pp. 248-255 ◽  
Author(s):  
Jérôme Avouac ◽  
Christophe Meune ◽  
Camille Chenevier-Gobeaux ◽  
Philippe Dieudé ◽  
Didier Borderie ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Risk Factors ◽  
Disease Activity ◽  
Myocardial Injury ◽  
Plasma Concentrations ◽  
Multivariate Logistic Regression Analysis ◽  
High Sensitivity ◽  
Joint Disease ◽  
Reactive Protein ◽  
Total Cohort

Objective.To measure concentrations of high-sensitivity cardiac troponin (HS-cTnT) and N-terminal pro-brain natriuretic peptide (NT-proBNP) in patients with rheumatoid arthritis (RA) and to examine correlates.Methods.The plasma concentrations of HS-cTnT and NT-proBNP were measured in consecutive patients with RA and compared to values obtained from age-matched and sex-matched healthy controls.Results.We included 236 unrelated patients with RA (192 females, 57 ± 13 yrs) and 213 controls (170 females, 55 ± 15 yrs). Seventy-one patients with RA were free of cardiovascular (CV) risk factors. HS-cTnT and NT-proBNP concentrations were significantly higher in the total cohort of patients with RA (p = 0.03 and p < 0.0001, respectively) and in the subgroup free of CV risk factors (p = 0.02 and p < 0.0001, respectively) compared to controls. In addition, both the total cohort of patients with RA and the subgroup free of CV risk factors were more likely to have levels above the cutoff concentrations of HS-cTnT (p = 0.003 and p = 0.007, respectively) and NT-proBNP (p = 0.0001 and p < 0.0001, respectively) than controls. Patients with RA and increased C-reactive protein (CRP) levels had higher HS-cTnT (p = 0.03) and NT-proBNP (p = 0.02) concentrations. HS-cTnT levels positively correlated with the 28-joint Disease Activity Score (DAS28-CRP; r = 0.2, p = 0.020). Multivariate logistic regression analysis indicated that increased HS-cTnT levels were independently associated with a DAS28-CRP > 5.1 (OR 11.8; 95% CI 1.6–35.5) and a body mass index > 30 kg/m2 (OR 2.7; 95% CI 1.3–5.5).Conclusion.HS-cTnT and NTproBNP are increased in patients with RA, independent of CV risk factors. The association between HS-cTnT, NT-proBNP, and CRP, together with the correlation between HS-cTnT and disease activity, support the link between myocardial injury/dysfunction and inflammation.

Do Radiographic Joint Damage and Disease Activity Influence Functional Disability Through Different Mechanisms? Direct and Indirect Effects of Disease Activity in Established Rheumatoid Arthritis

2013 ◽  
Vol 40 (9) ◽  
pp. 1505-1512 ◽  
Author(s):  
Sandhya C. Nair ◽  
Johannes W.J. Bijlsma ◽  
Jacobien H. van der Werf ◽  
Maaike J. van der Veen ◽  
Suzanne P. Linn-Rasker ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Functional Disability ◽  
Functional Decline ◽  
Joint Damage ◽  
Treatment Strategies ◽  
Joint Disease ◽  
Influence Functional ◽  
Over Time ◽  
Predictive Effect

Objective.To explore the relationship between rheumatoid arthritis (RA) disease activity and functional disability over time, considering indirect (predictive) and direct (concurrent) associations as well as the influence of radiographic joint damage and treatment strategy.Methods.Functional disability [Health Assessment Questionnaire (HAQ)], disease activity [28-joint Disease Activity Score (DAS28)], and radiographic joint damage [Sharp/van der Heijde score (SHS)] were measured in 4 consecutive randomized controlled trials with increasingly intensive (tight control) treatment strategies. Average followup time for the 3 cohorts was 97, 53, and 50 months, respectively. Next to current DAS28, the previous DAS28 was used to study the predictive effect of a change in DAS28 on progression of functional disability (HAQ). Finally, it was investigated whether SHS mediated the predictive effect of DAS28.Results.In patients treated with intensive treatment strategies, the progression of HAQ over time was statistically significantly less (p < 0.0001). The predictive influence of DAS28 on HAQ progression increased over the duration of the disease. SHS was not found to influence HAQ progression and did not mediate the predictive effect of DAS28. In the less intensively treated patients, the direct effect of disease activity decreased with disease duration, and contrarily, SHS did influence HAQ progression, but was not found to (fully) mediate the predictive effect of DAS28.Conclusion.In patients with RA treated with modern treatment strategies, there is less functional decline over time. Further, disease activity does predict functional decline but joint damage does not. This might indicate that factors associated with cumulative disease activity but not visible on radiographs can influence functional decline in patients with RA. This further underlines the importance of disease activity as a treatment target in early RA and in established RA.

scholarly journals Adalimumab, a human anti-TNF monoclonal antibody, outcome study for the prevention of joint damage in Japanese patients with early rheumatoid arthritis: the HOPEFUL 1 study

2013 ◽  
Vol 73 (3) ◽  
pp. 536-543 ◽  
Author(s):  
Tsutomu Takeuchi ◽  
Hisashi Yamanaka ◽  
Naoki Ishiguro ◽  
Nobuyuki Miyasaka ◽  
Masaya Mukai ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Early Rheumatoid Arthritis ◽  
Radiographic Progression ◽  
Joint Damage ◽  
Japanese Patients ◽  
High Disease Activity ◽  
Double Blind ◽  
American College Of Rheumatology ◽  
Modified Total Sharp Score

ObjectivesTo evaluate the efficacy and safety of adalimumab+methotrexate (MTX) in Japanese patients with early rheumatoid arthritis (RA) who had not previously received MTX or biologics.MethodsThis randomised, double-blind, placebo-controlled, multicentre study evaluated adalimumab 40 mg every other week+MTX 6–8 mg every week versus MTX 6–8 mg every week alone for 26 weeks in patients with RA (≤2-year duration). The primary endpoint was inhibition of radiographic progression (change (Δ) from baseline in modified total Sharp score (mTSS)) at week 26.ResultsA total of 171 patients received adalimumab+MTX (mean dose, 6.2±0.8 mg/week) and 163 patients received MTX alone (mean dose, 6.6±0.6 mg/week, p<0.001). The mean RA duration was 0.3 years and 315 (94.3%) had high disease activity (DAS28>5.1). Adalimumab+MTX significantly inhibited radiographic progression at week 26 versus MTX alone (ΔmTSS, 1.5±6.1 vs 2.4±3.2, respectively; p<0.001). Significantly more patients in the adalimumab+MTX group (62.0%) did not show radiographic progression (ΔmTSS≤0.5) versus the MTX alone group (35.4%; p<0.001). Patients treated with adalimumab+MTX were significantly more likely to achieve American College of Rheumatology responses and achieve clinical remission, using various definitions, at 26 weeks versus MTX alone. Combination therapy was well tolerated, and no new safety signals were observed.ConclusionsAdalimumab in combination with low-dose MTX was well tolerated and efficacious in suppressing radiographic progression and improving clinical outcomes in Japanese patients with early RA and high disease activity.

scholarly journals Predictive Factors Related to the Efficacy of Golimumab in Patients with Rheumatoid Arthritis

2015 ◽  
Vol 8 ◽  
pp. CMAMD.S22155 ◽  
Author(s):  
Katsuaki Kanbe ◽  
Junji Chiba ◽  
Yasuo Inoue ◽  
Masashi Taguchi ◽  
Akiko Yabuki
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Predictive Factors ◽  
Disease Duration ◽  
Radiographic Progression ◽  
Serum Levels ◽  
Serum Concentrations ◽  
Regression Analyses ◽  
Tnf Α ◽  
Baseline Characteristics

In order to investigate the predictive factors related to clinical efficacy and radiographic progression at 24 weeks by looking at the serum levels of tumor necrosis factor (TNF)-α and interleukin (IL)-6 including baseline characteristics in patients with rheumatoid arthritis (RA) treated with golimumab, serum concentrations of TNF-α and IL-6 were analyzed every 4 weeks up to 24 weeks in 47 patients treated with golimumab. Baseline levels of the Disease Activity Score 28 C-reactive protein (DAS28-CRP) and Simplified Disease Activity Index (SDAI) scores were also assessed. Radiographic progression using the van der Heijde-modified Sharp (vdH-S) score was assessed in 29 patients. Multiple regression analyses related to the DAS28-CRP score and delta total sharp score at 24 weeks was undertaken using the baseline characteristics of patients and serum concentrations of matrix metalloproteinase (MMP)-3, TNF-α, and IL–6. The DAS28-CRP score and SDAI decreased significantly at 4 weeks up to 24 weeks compared with baseline. Serum levels of TNF-α were not changed significantly up to 24 weeks compared with baseline, but those of IL-6 decreased significantly at 4 weeks up to 8 weeks. Multiple regression analyses showed that disease duration and serum levels of MMP-3 were related significantly to the DAS28-CRP score at 24 weeks. Radiographic progression was related significantly to disease duration with regard to joint space narrowing and bone erosion. However, serum levels of TNF-α and IL-6 were not correlated significantly with the DAS28-CRP score and radiographic progression. These data suggest that decreasing serum levels of IL-6 significantly, MMP-3, and disease duration are predictive factors for RA activity in patients taking golimumab.

scholarly journals Serum levels of reactive oxygen metabolites at 12 weeks during tocilizumab therapy are predictive of 52 weeks-disease activity score-remission in patients with rheumatoid arthritis

2019 ◽  
Vol 3 (1) ◽  
Author(s):  
Arata Nakajima ◽  
Keiichiro Terayama ◽  
Masato Sonobe ◽  
Yasuchika Aoki ◽  
Hiroshi Takahashi ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Disease Activity Score ◽  
Activity Index ◽  
Multivariate Logistic Regression Analysis ◽  
Reactive Oxygen ◽  
Serum Levels ◽  
Activity Score ◽  
Reactive Oxygen Metabolites ◽  
Oxygen Metabolites

Abstract Background To verify whether serum levels of reactive oxygen metabolites (ROM) are predictive of future clinical remission in patients with rheumatoid arthritis (RA) receiving tocilizumab (TCZ) therapy. Methods A total of 46 patients with RA receiving TCZ therapy were enrolled in this study. Patients were divided into remission and non-remission groups based on disease activity score 28 (DAS28)-erythrocyte sedimentation rate (ESR) or clinical disease activity index (CDAI) at 52 weeks. Associations between serum levels of ROM, C-reactive protein (CRP), and matrix metalloproteinase-3 (MMP-3) at 4 and 12 weeks and the remission by DAS28-ESR and CDAI at 52 weeks were investigated. Results There were no significant differences in CRP and MMP-3 between DAS- or CDAI-remission and non-remission groups at 12 weeks. However, ROM in DAS-remission group were significantly lower than those in the non-remission group. For ROM, the area under the curve of the receiver operating characteristic curve was 0.735 and the cut-off value that distinguished DAS-remission group from non-remission group was 305.5 U. Carr (sensitivity: 70.0%, specificity: 72.2%). A multivariate logistic regression analysis revealed that ROM at 12 weeks was associated with DAS-remission at 52 weeks (odds ratio: 6.067, 95% confidence interval: 1.305–28.203). Conclusion Serum levels of ROM at 12 weeks during TCZ therapy may be predictive of DAS-remission at 52 weeks in patients with RA.

scholarly journals Evaluation of rituximab therapy in real clinical practice (according to the OREL registry of patients with rheumatoid arthritis

2019 ◽  
Vol 57 (3) ◽  
pp. 274-279 ◽  
Author(s):  
A. S. Avdeeva ◽  
A. M. Satybaldyev ◽  
N. V. Demidova ◽  
N. Yu. Nikishina ◽  
E. V. Gerasimova ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Clinical Practice ◽  
Disease Activity ◽  
Acute Phase ◽  
Active Rheumatoid Arthritis ◽  
Serum Levels ◽  
Biologic Agent ◽  
Acute Phase Reactants ◽  
Reactive Protein ◽  
Real Clinical Practice

Objective:to analyze therapy with rituximab (RTM) in real clinical practice according to the data available in OREL registry of patients with active rheumatoid arthritis (RA).Subjects and methods. The analysis included 349 patients. All the patients received RTM: 340 – the original drug (MabThera®) and 9 – the biosimilar Acellbia®. 263 patients (75.4%) received RTM in combination with disease-modifying anti-rheumatic drugs (DMARDs) and 86 (24.6%) – RTM as monotherapy.Results and discussion. Of the 349 patients included in the analysis, 272 (77.9%) patients received RTM as the first biologic agent (BA) (263 patients were treated with the original drug and 9 – with the biosimilar) and 77 (22.1%) patients had previously used the BA. The majority of patients (n=205 (58.7%)) received three or more; 109 (31.2%) patients – one, and 35 (10%) – two RTM courses of RTM therapy. RTM caused a significant reduction in disease activity just after the first therapy course and in the levels of acute-phase reactants (C-reactive protein (CRP) and ESR); after the fifth therapy course, median CRP concentration decreased by 1.4 times and amounted to 7 [1.2; 17.9] mg/l and that of ESR reduced by 1.8 times and was 10 [5; 20] mm/hr (p<0.05).Conclusion.The analysis of RTM therapy in RA patients in real clinical practice demonstrated that in most cases RTM was given as the first BA, in combination with DMARDs, the main agent of which was methotrexate. The use of RTM was accompanied by a significant reduction in disease activity and in the serum levels of acute-phase reactants and autoantibodies.

scholarly journals Differential Regulation and Correlation between Galectin-9 and anti-CCP antibody (ACPA) in Rheumatoid Arthritis Patients

2020 ◽  
Author(s):  
Yuya Fujita ◽  
Tomoyuki Asano ◽  
Naoki Matsuoka ◽  
Jumpei Temmoku ◽  
Shuzo Sato ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Immune Responses ◽  
Disease Activity ◽  
Disease Activity Score ◽  
Clinical Phenotype ◽  
Joint Damage ◽  
Serum Levels ◽  
Enzyme Linked Immunosorbent Assay ◽  
Matrix Metalloproteinase 3 ◽  
The Status

Abstract Background: Galectin-9 (Gal-9) is involved in the regulatory process of immune responses or inflammation. The aim of the present study is to characterize circulating Gal-9 in patients with rheumatoid arthritis (RA) and its relationship with RA disease activity and phenotype. Methods: A total 116 RA patients and age-matched healthy controls (n=31) were included in this study. Disease activity of RA patients were determined by Disease Activity Score of 28 joint scoring system (DAS28-ESR). Levels of Gal-9 in serum were determined by enzyme-linked immunosorbent assay (ELISA). Results: Serum levels of Gal-9 were significantly higher in patients with RA compared to those in controls (median 7577 pg/ml; [interquartile range (IQR); 5570–10201] versus 4738 pg/ml [IQR; 4267–5630], p=0.001). There were significant differences in serum Gal-9 between RA patients with and without RA-ILD (9606 pg/ml [IQR: 8522–12167] versus 7078 pg/ml [IQR: 5225–9447], p<0.001) or those with and without advanced joint damage (Stage Ⅱ-Ⅳ, 9606 pg/ml [IQR: 8522–12167] versus 7078 pg/ml [IQR: 5225–9447], p<0.001). Although serum levels of Gal-9 correlated with the titers of ACPA (r=0.275, p=0.002), levels of ACPA titers conferred the different relationship, between serum Gal-9 and inflammatory mediators or RA disease activity. Although Gal-9 was correlated with ACPA titers (r=0.508, p=0.002), there was no correlation between Gal-9 levels and erythrocyte sedimentation rate (ESR), matrix metalloproteinase-3 (MMP-3) or DAS28-ESR in RA patients with high titers of ACPA (>200u/ml). Conversely, Gal-9 was correlated with MMP-3 (r=0.300, p=0.007) or DAS28-ESR (r=0.331, p=0.004) not with ACPA titer in RA patients with low titers of ACPA titers (<200U/ml). Conclusions: Serum levels of Gal-9 were increased in RA patients and associated with RA disease activity in RA patients without high titers of ACPA. The levels of ACPA titers may influence the values of circulating Gal-9 in RA patients with various clinical phenotype. These data suggest that Gal-9 possessed the properties of proinflammatory or arthropathic biomarker under the status of ACPA titers.

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