Long-standing Rheumatoid Arthritis Patients Research Articles

The association between disease duration and mood disorders in rheumatoid arthritis patients.

The mood disorders have been recognized as common comorbidities of rheumatoid arthritis (RA), however unknown in patients with different RA courses. Therefore, we aimed to investigate the status of mood disorders in early RA and non-early RA patients and further identify the associated factors for mood disorders. Self-rating anxiety scale (SAS) and self-rating depression scale (SDS) were assessed in all enrolled RA patients. Besides clinical assessments, power Doppler and greyscale (GS) ultrasound of 28 joints was performed. The frequency of mood disorders was compared between early RA and non-early RA patients. Multivariate regression was used to identify the associated factors for mood disorders. Tow hundred one RA patients were enrolled, with 76 early RA (disease duration ≤ 2years) and 125 non-early RA (disease duration > 2years). Mood disorders (depression and/or anxiety) were found in 42 (20.9%) patients. Depression was more frequently observed in early RA than non-early RA patients (26.3% vs. 14.4%, P = 0.036). A similar trend for anxiety was also observed in early RA compared to non-early RA patients, although the difference was insignificant (13.2% vs. 5.6%, P = 0.062). Disease duration (OR = 0.991, 95% CI 0.985-0.998, P = 0.009), health assessment questionnaire disability index (HAQ-DI) (OR = 1.045, 95% CI 1.005-1.086, P = 0.029) and GS synovitis score (OR = 1.065, 95% CI 1.017-1.115, P = 0.007) were identified as factors associated with depression. Disease duration (OR = 0.981, 95% CI 0.967-0.995, P = 0.009), HAQ-DI (OR = 1.071, 95% CI 1.013-1.133, P = 0.017) and GS synovitis score (OR = 1.072, 95% CI 1.012-1.136, P = 0.019) were identified to be associated with anxiety. Depression and anxiety were almost doubled in frequency in early RA than in long-standing RA patients. RA patients with short disease duration, high HAQ-DI and GS score were more likely to be in depression and anxiety. Key Points • Mood disorders were more frequent in early RA than non-early RA patients. • More attention to psychological status is needed in RA patients. • RA patients with short disease duration, poor physical function and severe synovitis were more likely to have depression and/or anxiety.

Chronic inflammation-induced senescence impairs immunomodulatory properties of synovial fluid mesenchymal stem cells in rheumatoid arthritis

BackgroundAlthough the immunomodulatory properties of mesenchymal stem cells (MSCs) have been highlighted as a new therapy for autoimmune diseases, including rheumatoid arthritis (RA), the disease-specific characteristics of MSCs derived from elderly RA patients are not well understood.MethodsWe established MSCs derived from synovial fluid (SF) from age-matched early (average duration of the disease: 1.7 years) and long-standing (average duration of the disease: 13.8 years) RA patients (E-/L-SF-MSCs) and then analyzed the MSC characteristics such as stemness, proliferation, cellular senescence, in vitro differentiation, and in vivo immunomodulatory properties.ResultsThe presence of MSC populations in the SF from RA patients was identified. We found that L-SF-MSCs exhibited impaired proliferation, intensified cellular senescence, reduced immunomodulatory properties, and attenuated anti-arthritic capacity in an RA animal model. In particular, E-SF-MSCs demonstrated cellular senescence progression and attenuated immunomodulatory properties similar to those of L-SF-MSC in an RA joint-mimetic milieu due to hypoxia and pro-inflammatory cytokine exposure. Due to a long-term exposure to the chronic inflammatory milieu, cellular senescence, attenuated immunomodulatory properties, and the loss of anti-arthritic potentials were more often identified in SF-MSCs in a long-term RA than early RA.ConclusionWe conclude that a chronic RA inflammatory milieu affects the MSC potential. Therefore, this work addresses the importance of understanding MSC characteristics during disease states prior to their application in patients.Graphical abstract

Pulmonary abnormalities on high-resolution computed tomography in patients with long standing rheumatoid arthritis

Background. Rheumatoid arthritis (RA) is a systemic inflammatory disease, associated with a number of extra-articular organ manifestations. Pulmonary involvement is a frequent and severe extraarticular manifestations of rheumatoid arthritis. RA can affect lung parenchyma, airways and pleura. Objectives. To identify RA-related lung disease on chest computed tomography (CT). Material and methods. We performed high-resolution computed tomography (HRCT) on a total of 92 patients with longstanding RA. Results. The subjects were predominantely female (79.3%), the age at entry was 63.77 ±11.56 years, and 42.9% had a history of smoking. Disease duration was 15.00±11.55 years. Pulmonary CT abnormalities were found in 71 of the 92 patients (77.2%). The most common HRCT anomalies were: linear attenuation (reticulation) (52.11%), bronchiectasis andbronchial wall thickening (45%), nodular attenuation (39.43%) and pleural involvement (pleural effusion or thickening) (39.43%). Conclusions. We conclude that RA-related lung disease was commonly detected on chest CT imaging in longstanding RA patients.

Central sensitisation features are associated with neuropathic pain-like symptoms in patients with longstanding rheumatoid arthritis: a cross-sectional study using the central sensitisation inventory.

Several studies have indicated that arthralgia may be driven by central sensitisation. Central sensitivity syndrome (CSS) is a concept that unifies various symptoms due to central sensitisation. Recently, the central sensitisation inventory (CSI) was developed as a screening questionnaire to detect CSS. Using the CSI, we examined the prevalence, the clinical characteristics of CSS, and the association between CSS and neuropathic pain (NP)-like symptoms among rheumatoid arthritis (RA) patients. The CSI was administered to 240 RA outpatients. We evaluated their disease activity and several potentially relevant patient-reported outcomes. We compared the clinical parameters depending on the severity of CSS and examined the effect of the CSI score on NP-like symptoms among the relevant clinical parameters using multivariate analyses. The mean disease duration was 9.58 ± 7.76 years. Eighteen (7.5 %) patients had CSS, which was associated with evaluator global assessment (EGA) (odds ratio (OR) 0.860); fibromyalgia symptom scale (OR 1.46); painDETECT questionnaire score (OR 1.24); hospital anxiety and depression scale-anxiety (OR 1.35); and physical (OR 0.898), mental (OR 0.828), and role-social (OR 0.946) component summary scores on the Short-Form 36-Item Health Survey. CSI score was the factor that contributed most to NP-like symptoms (p=0.000, β=0.266). NP-like symptoms might be one of the symptoms of CSS in longstanding RA patients. In longstanding RA patients who have disproportionately greater NP-like symptoms and/or widespread pain compared with degree of inflammation, detecting CSS using CSI might help to understand the pathogenesis of patients.

Pulmonary abnormalities, clinically, functionally, and radiologically in patients with rheumatoid arthritis: correlation with duration and disease activity

Background Rheumatoid arthritis (RA) as a systemic autoimmune disease has articular and extra-articular manifestations affecting about 50%. All anatomic structures of the lung were affected by RA. It has been recommended that patients with RA must be surveyed for lung involvement, through the use of chest radiographs, pulmonary function tests (PFTs), and clinical assessment.Aim To investigate chest abnormalities in RA patients.Patients and methods Our research included 174 RA patients, subjected to history taking, clinical examination, laboratory investigations, and chest assessment by plain chest radiograph, high-resolution computed tomography (CT), and PFTs. RA activity was assessed by disease activity scoring (DAS28). The patients were divided into two groups: group A (early RA) and group B (late RA).Results Respiratory symptoms were reported in 20.7 and 42.7% in groups A and B, respectively. Respiratory functions were significantly reduced in group B. Patients with abnormal CT findings was significantly increased in group B when compared with group A (57.3 vs. 30.4%). Patients with positive chest CT findings had significantly high positive rheumatoid factor (RF), positive anti-cyclic citrullinated peptide, and significant increase of DAS28 (moderate and severe DAS28), and significantly longer disease duration when compared with patients with negative CT findings. There was a significant, inverse correlation between each of DAS28 and disease duration and each of respiratory function tests.Conclusion CT abnormalities of the respiratory system were more prevalent in long-standing RA patients. Pulmonary functions were significantly reduced in those patients with increased levels of C reactive protean (CRP) and erythrocyte sedimentation rate (ESR) and high DAS28.

Disease activity is associated with cognitive impairment in patients with rheumatoid arthritis.

To investigate the association between disease activity and cognitive impairment in patients with rheumatoid arthritis (RA). A total of 464 patients from the rheumatoid arthritis registry of two academic centers, Siriraj and Phramongkutklao hospitals, were included. Demographic, clinical, and laboratory data related to disease activity and functional status were collected. Cognitive function was assessed using the Thai version of the Montreal Cognitive Assessment (MoCA-T). Subjects were classified as cognitively impaired if they scored less than 25. Most subjects (85%) were female with a mean age ± SD of 59.2 ± 11.4years old and a median (range) educational level of 9 (4-14) years. They were long-standing RA patients (median disease duration (range) of 9.9 (5.1-16.6) years) and had moderate cumulative disease activity (mean DAS28 ± SD of 3.5 ± 0.81) and mild functional impairment (median HAQ (range) 0.5 (0.13-1.10)). Seventy percent of the patients were classified as having cognitive impairment. The patients with cognitive impairment significantly impaired in all domains, especially in visuospatial/executive, language, and abstraction. In multiple logistic regression analyses, old age (RR 3.45, 95% CI 2-6, p < 0.001), low education (RR 10.8, 95% CI 5.3-22.1, p < 0.001), and high cumulative disease activity (RR 2.2, 95% CI 1.07-4.7, p = 0.033) were independently associated with cognitive impairment. High cumulative RA disease activity is associated with cognitive impairment. Therefore, treat-to-target aimed at low disease activity or remission may be beneficial for preventing cognitive decline in RA patients.

Low body mass index in long standing rheumatoid arthritis: relation to RA disease activity and functional indices

The aim of the work was to study the relationship between the body mass index (BMI) in longstanding rheumatoid arthritis (RA) and RA disease activity and functional indices. This study included 105 RA patients. For all patients, we recorded the presence of erosions on radiographs, the presence of subcutaneous nodules (SCN), the 28-tender joint count (TJC), 28-swollen joint count (SJC) scores, the visual analogue scale (VAS), physicians' global assessments (PhGA), the erythrocyte sedimentation rate (ESR), and the rheumatoid factor (RF). The disease activity index (DAS28) and BMI were calculated and current treatment was recorded. Patients were divided into two groups: group I: BMI 25. Group I included 32 (30.5%) patients, whereas group II included 73 (69.5%) patients. There were statistically significant differences between the two groups regarding each of the following: SJC (p=0.006), erosions (p=0.006), DAS28 (p=0.016) and PhGA (p=0.007). All were higher in group I (underweight and normal) than in group II (overweight and obese). No statistically significant differences emerged regarding age (p=0.11), smoking (p=0.69), disease duration (p=0.46), TJC (p=0.14), SCN (p=1.00), HAQ (p=0.26), VAS (p=0.16), ESR (p=0.25), RF (p=0.54) and steroid cumulative dose (p=0.08). Low BMI in longstanding RA patients may indicate more active and erosive disease and it may be considered as a poor prognostic factor.

MRI assessment of erosion repair in patients with long-standing rheumatoid arthritis receiving double-filtration plasmapheresis in addition to leflunomide and methotrexate: a randomized controlled trial.

The objective of this study is to investigate whether the addition of double-filtration plasmapheresis (DFPP) to leflunomide and methotrexate repairs MRI bone erosion in patients with long-standing rheumatoid arthritis (RA). Seventy-two patients with highly active RA of > 3years' duration were randomized to receive DFPP in addition to DMARDs (leflunomide and methotrexate) or DMARDs. Contrast-enhanced MRI of the right wrist was performed at months 0, 6, and 12. MRI bone erosion, synovitis, and bone edema were scored with validated methods. The primary endpoint was the change in MRI bone erosion over 12months. Patients treated with DFPP in addition to DMARDs demonstrated significantly greater decrease in MRI erosion score compared with those treated with DMARDs, being 11.3 ± 9.6 at month 12, compared with 16.9 ± 8.3 in patients with DMARDs (P < 0.001), and compared with 14.4 ± 9.6 at baseline (P < 0.001). 84.2% of patients treated with DFPP in addition to DMARDs demonstrated a decrease in MRI erosion score. Synovitis and bone edema improved significantly with DFPP in addition to DMARDs compared with DMARDs at months 6 and 12. (1.05 ± 1.7 and 2.0 ± 3.9 compared with 8.0 ± 1.4 and 12.6 ± 7.9 at month 12). Patients without synovitis and bone edema reached in 55.3% among patients with DFPP in addition to DMARDs. This study demonstrated that DFPP combination therapy significantly decreased bone erosion and received the primary goal of repair of erosions through abrogating MRI inflammation (synovitis and bone edema) in long-standing RA patients with high disease activity. The findings suggest that addition of DFPP is associated with repair of erosions and further suppression of inflammation.

The influence of fibromyalgia on achieving remission in patients with long-standing rheumatoid arthritis.

To investigate the influence of fibromyalgia (FM) on achieving remission defined on the basis of the Simplified Disease Activity Index (SDAI) remission criteria in patients with long-standing rheumatoid arthritis (RA). This observational longitudinal cohort consisted of long-standing RA patients being treated with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) or biological DMARDs (bDMARDs). After 6months of follow-up, the patients fulfilling or not fulfilling the remission criteria were identified and compared with each other in terms of the presence of FM, neuropathic pain, and other comorbidities. At the end of the 6-month observation period, 24 of the 117 patients (20.4%) met the SDAI remission criteria. Logistic regression analysis showed that the modified Rheumatic Disease Comorbidity Index (mRDCI) (p=0.0001), the FM presence (p=0.0001), and the 36-item short-form health survey Mental Component Summary (SF-36 MCS) Score (p=0.0088) were the strongest predictors of not being in SDAI remission. None of the patients with concomitant FM (17.1%) achieved SDAI remission. In comparison with the non-FM patients, the patients with RA and FM patients had worse scores on the SF-36 MCS (p=0.011), on the sleep Visual Analogue Scale (VAS) (p=0.018), on the self-counts of tender joints (p=0.039), and on the PainDetect Questionnaire (PDQ) (p=0.001). To avoid over treatment, an assessment of FM should be considered in RA patients who do not fulfil the remission criteria.

Prevalence of left ventricular dysfunction in rheumatoid arthritis.

Background:Rheumatoid arthritis (RA) is a polyarticular disorder with many extra-articular features. Cardiovascular disorders, including heart failure (HF), are the leading causes of mortality in RA patients. We studied the prevalence of left ventricular dysfunction (LVD) in patients with RA.Materials and Methods:In this cross-sectional study, we evaluated 100 consecutive patients with RA (aged >18 years and duration >1 year) for the presence of LVD. We excluded patients with known cardiac and systemic disorders that may contribute to LVD. LVD is defined by the presence of either left ventricular systolic dysfunction (LVSD) or left ventricular diastolic dysfunction (LVDD), evaluated by the echocardiography. Descriptive statistics and relevant tests were used to analyze the results.Results:The study participants (n = 100; 80F and 20M) had a mean age of 45 ± 11.8 years, duration of disease 7.4 ± 5.4 years, and disease activity score of 3.5 ± 1.1. A total of 46 patients had symptoms of HF, but only 14% of them had signs of HF. LVD was seen in 59 (LVSD-4, LVDD-50, and both together in 5) patients, and none of the participants had severe grades of LVSD and LVDD. LVD showed no relation to the age of the patients (P = 0.186) and it was more with increasing duration of RA (P < 0.001) and higher disease activity (P = 0.042).Conclusion:LVD is more common in RA patients, which increases the associated morbidity and mortality. Higher threshold is required by the family practitioners to perform a screening echocardiography in long-standing RA patients.

Adverse outcomes following hand surgery in patients with rheumatoid arthritis

Up to 70% of patients with long-standing rheumatoid arthritis (RA) may present with rheumatic hand disease and benefit from hand surgical procedures (HSPs). Through retrospective review, the present study aimed to report HSPs in RA patients at a tertiary care centre to identify patient adverse outcomes (AOs) and their predictors. From 1989 to 2013, 96 patients who underwent ≥1 HSP(s) were identified from two local registries; their clinical records were independently reviewed by two trained physicians (surgeon and clinical) who used a standardized format. AOs were defined by consensus; data abstracter agreement was found in 90% of cases. Descriptive statistics were used in addition to Kaplan-Meier curves to determine the time to each AO, while logistic regression models were used to determine predictors of AOs. At first HSP, 89.6% of patients were female, had a mean (± SD) age of 49.1±12 years, a disease duration of 12.2±7.2 years, 93.6% were positive for rheumatoid factor and 24% were receiving intensive treatment. A total of 130 HSPs were performed: the most frequent interventions were arthrodesis (25.4%), resection of the ulnar head (15.4%) and tenorrhaphy (14.6%). During follow-up, 33 AOs were reported in 27 (28.1%) patients, 87% of which occurred after the first HSP. The most frequent AO subsets were impaired wound healing (18.2%) and exposed pin (15.2%). Longer disease duration at first HSP (OR 3.07 [95% CI 1.04 to 9.08]; P=0.04) and intensive treatment (OR 1.08 [95% CI 1.002 to 1.156]; P=0.045) were predictors of AOs. The optimal disease duration cut-off to predict AOs was 20.1 years. Early referral of long-standing RA patients for hand surgery, along with less aggressive treatment, favoured improved surgical outcomes.

Periodontitis is associated with rheumatoid arthritis: a study with longstanding rheumatoid arthritis patients in Korea.

Background/Aims:A cross-sectional study was undertaken to investigate the association between severity of periodontitis and clinical manifestation of rheumatoid arthritis (RA).Methods:Two hundred sixty-four RA patients and 88 age- and sex-matched controls underwent dental exam. Additionally, clinical manifestations including disease activity and anti-citrullinated protein antibodies were evaluated in RA patients.Results:The prevalence of moderate or severe periodontitis was higher in RA patients compared to controls (63.6% vs 34.1%, p < 0.001). In markers of periodontal inflammation, bleeding on probing was correlated with disease activity score 28 (r = 0.128, p = 0.041), RA disease duration (r = 0.211, p = 0.001), erythrocyte sedimentation rate (ESR; r = 0.141, p = 0.023), anti-cyclic citrullinated peptide antibody (r = 0.183, p = 0.009), and anti-citrullinated α-enolase peptide-1 antibody (r = 0.143, p = 0.025). Gingival index was correlated with RA duration (r = 0.262, p < 0.001), ESR (r = 0.162, p = 0.009), anti-cyclic citrullinated peptide antibody (r = 0.203, p = 0.004) and anti-citrullinated α-enolase peptide-1 antibody (r = 0.225, p < 0.001). Periodontal structural damage represented by probing pocket depth and clinical attachment level were less in RA patients with human leukocyte antigen (HLA)-DRB1 shared epitope compared than those without shared epitope (p = 0.005 and p =0.006, respectively).Conclusions:The prevalence of moderate or severe periodontitis was increased in RA patients compared to controls. Periodontal inflammation was correlated with RA disease duration, ESR, and anti-citrullinated protein antibodies. Periodontal structural damage was less in RA patients with HLA-DRB1 shared epitope.

Is ultrasound a better target than clinical disease activity scores in rheumatoid arthritis with fibromyalgia? A case-control study.

ObjectivesOur goal is to study the correlations among gray-scale seven-joint ultrasound score (GS-US7), power Doppler seven-joint ultrasound score (PD-US7), disease activity score-28 joints (DAS28), simplified disease activity index (SDAI) and clinical disease activity index (CDAI) in patients with and without fibromyalgia (FM).MethodsA matched case-control study included all patients consecutively seen in the Rheumatoid Arthritis (RA) Clinic. Participants were allocated into one of two groups: RA with FM and RA without FM. Ultrasound (US) and clinical scoring were blinded for the presence of FM. Medians and proportions were compared by Mann-Whitney’s test and McNemar’s test, respectively. Spearman’s rank correlation coefficients (rs) were calculated among clinical and US scores and differences were tested by r-to-z transformation test.ResultsSeventy-two women were included, out of 247 RA patients, mostly white, with median (IQR) age of 57.5 (49.3–66.8) years, with RA symptoms for 13.0 (6.0–19.0) years and FM symptoms for 6.0 (2.0–15.0) years. Disease-modifying antirheumatic drugs, non-steroidal anti-inflammatory drugs and prednisone use was comparable between groups. Objective activity parameters were not different between groups. RA patients with FM had greater DAS28, SDAI and CDAI but similar GS-US7 and PD-US7. GS-US7 correlated with DAS28, SDAI and CDAI in patients with and without FM (rs = 0.36–0.57), while PD-US7 correlated with clinical scores only in patients without FM (rs = 0.35–0.38).ConclusionTo our knowledge, this is the first study to demonstrate that ultrasound synovitis scores are not affected by FM in RA patients. PD-US7 performed better than GS-US7 in long-standing RA patients with DAS28, SDAI or CDAI allegedly overestimated due to FM. Since sonographic synovitis predicts erosion better than swollen joint count, C-reactive protein and erythrocyte sedimentation rate, US should be considered a promising treatment target in RA patients with FM.

Increased risk of insulin resistance in long-standing rheumatoid arthritis patients

Increased risk of insulin resistance in long-standing rheumatoid arthritis patients

Memory B cell subsets and plasmablasts are lower in early than in long-standing rheumatoid arthritis.

BackgroundAlterations of B cell subset distribution have been described in the peripheral blood (PB) of rheumatoid arthritis (RA) patients, but no data are available on differences between the onset and the established phases of the disease. The purpose of the study was to clarify whether a peculiar distribution of B cell subsets characterizes RA onset, thus leading to a more favorable clinical response to treatment, and to evaluate the possible association of a particular B cell subpopulation with response to therapy.Results122 RA patients were enrolled: 25 had symptom duration less than 3 months and were defined as having “very early RA” (VERA), and 43 had symptom duration from more than 3 months up to one year (early-RA: ERA). The other 54 RA patients had long-standing RA (LSRA). At baseline and at 6-month follow-up visit peripheral blood samples were collected and analyzed by flow cytometry for the distribution of circulating B cell subsets by staining with surface markers CD45, CD19, CD38, CD27 and IgD and intracellular marker ZAP70.VERA and ERA patients showed higher percentages and absolute counts of circulating antigen inexperienced naïve B cells (IgD + CD27-) and lower percentages and absolute numbers of double negative (IgD-CD27-) memory B cells and plasmablasts (CD38 + CD27+) compared to LSRA patients. At the multivariate analysis, a higher frequency of naïve B cells (IgD + CD27-) at baseline arose as significant predictor of CDAI remission, together with “having VERA disease” and a low disease activity at baseline.ConclusionsThe onset of RA is characterized by higher percentages and absolute numbers of naïve B cells and lower numbers of plasmablasts and double negative memory B cells compared to established RA. Naïve B cells could represent a promising biomarker of outcome.Electronic supplementary materialThe online version of this article (doi:10.1186/s12865-014-0028-1) contains supplementary material, which is available to authorized users.

AB0291 Association between Pentosidine, an Advanced Glycation End-Product, and Disease Activity in Patients with Untreated Rheumatoid Arthritis. A Preliminary Report

BackgroundSerum and urinary pentosidine, an advanced glycation end-product (AGE), levels were increased in patients with rheumatoid arthritis (RA) when compared with healthy controls. Antirheumatic medications including prednisolone, methotrexate and anti-tumor...

AB0384 Effectiveness and Adherence to Adalimumab Treatment in Patients with RA in Eastern Europe: Results of the Eviraeast Observational Study

BackgroundEviraEAST was a prospective, single-arm, multicountry observational study conducted in 6 Eastern European countries and Israel.ObjectivesThe aim was to evaluate clinical outcomes, safety, and compliance with adalimumab (ADA) therapy in...

Induction Therapy with Combination TNF Inhibitor and Methotrexate in Early Rheumatoid Arthritis

With the introduction of more objective disease activity measures and the development of biological therapies, there were dramatic changes in the treatment of rheumatoid arthritis (RA). The combination therapy with tumor necrosis factor (TNF) inhibitor and methotrexate (MTX) has unprecedentedly improved prognosis and outcomes, and very low disease activity or remission has been achievable goal in RA. Although the concept of remission induction and maintenance was first discussed in longstanding RA patients, several clinical trials have demonstrated that there is a therapeutic window of opportunity, and early effective control of inflammation in early RA could lead to less joint damage and better long-term outcomes. Emerging evidence suggests that early combination therapy with TNF inhibitor and MTX leads to rapid clinical remission and thereby improved quality of life. Furthermore, remission status may be sustained in some patients even if a TNF inhibitor is discontinued after sustained remission in early RA patients. While there are many potential benefits of early remission induction therapy with the combination of a TNF inhibitor and MTX, the best therapeutic regimen and strategy for remission induction and maintenance in early RA remain controversial. There are no data to decide a priori when and in whom TNF blocker drugs are indicated in early disease-modifying anti-rheumatic drug (DMARD)-naïve RA.

Response to ‘Adipokines, inflammation, insulin resistance, and carotid atherosclerosis in patients with rheumatoid arthritis’

In a recent report in Arthritis Research & Therapy, Kang and colleagues [1] assessed a series of patients with rheumatoid arthritis (RA) to establish whether adipokines could be a link between inflammation, insulin resistance, and atherosclerosis in RA. We have noticed that Kang and colleagues did not pay attention to our former studies on the same issue. In this regard, in the last decade, we conducted a series of studies on insulin resistance and adipokines in a cohort of Spanish patients with long-standing RA, undergoing anti-tumor necrosis factor-alpha (anti-TNF-α) infliximab therapy because of severe disease, refractory to conventional disease-modifying anti-rheumatic drugs [2-6]. Kang and colleagues described that resistin was associated with erythrocyte sedimentation rate (ESR) (r = 0.322, P <0.001), C-reactive protein (CRP) (r = 0.209, P = 0.004), and increased disease duration (r = 0.176, P = 0.014) [1]. These data are not new. We previously reported a close association between laboratory markers of inflammation, particularly CRP and resistin levels [3]. In our series, we found a significant association between the mean ESR (r = 0.405, P = 0.03) and CRP (r = 0.571, P = 0.0005) from disease diagnosis and ESR (r = 0.486, P = 0.004), CRP (r = 0.599, P = 0.0005), and platelet count (r = 0.559, P = 0.0007) at the time of the study and resistin levels [3]. These findings, along with these new data described by Kang and colleagues, highlight the potential role of resistin in the inflammatory cascade in RA. Kang and colleagues also found a positive correlation between adiponectin and ESR (r = 0.162, P = 0.025) [1]. Prior to these results, in our series of patients with severe and active disease despite anti-TNF-α therapy, we observed that high-grade inflammation was independently and negatively correlated with circulating adiponectin concentrations [4]. CRP levels correlated with circulating adiponectin concentrations (partial r (pr) = −0.370, P = 0.04), independently of age and gender [4]. In contrast, low adiponectin levels clustered with metabolic syndrome features that contribute to atherogenesis in RA [4]. Adiponectin concentrations correlated with triglycerides/high-density lipoprotein (HDL) cholesterol ratios (pr = −0.396, P = 0.03), total cholesterol/HDL cholesterol ratios (pr = −0.444, P = 0.01), and high fasting plasma glucose levels (pr = −0.366, P = 0.04), independently of CRP levels and the body mass index [4]. These results also suggest an implication of adiponectin in the development of cardiovascular disease in RA. In the series by Kang and colleagues, leptin was associated with homeostasis model assessment-estimated insulin resistance (r = 0.369, P <0.001) [1]. In our series of RA patients with active disease despite anti-TNF-α therapy, there was a positive correlation between body mass index of RA patients and serum leptin levels (r = 0.665, P <0.001) [5]. Also, a significant correlation of leptin with biomarkers of endothelial activation (vascular cell adhesion molecule-1; r = 0.349, P = 0.04) was observed [5]. However, no significant correlations between leptin levels and disease duration, ESR and CRP levels, disease activity score using 28 joint counts, lipids, insulin sensitivity, resistin, adiponectin, or the cumulative prednisone dose at the time of the study were found [5]. Therefore, in Western patients with severe and active RA, leptin levels seem to be related to adiposity [5]. However, in our series, circulating visfatin levels were unrelated to disease activity, adiposity, or metabolic syndrome [6]. Although adipokines have been demonstrated to exert a key role in the interface between obesity, inflammation, insulin resistance, and atherosclerosis in the general population, we agree with Kang and colleagues that information on their potential contribution is still limited in RA. In this regard, in Western individuals with RA, adipokines have not been demonstrated to represent a significant risk factor for indirect measures of organic arterial wall atherosclerotic damage, as assessed by carotid intima-media thickness in our cohort of long-standing active RA patients undergoing infliximab treatment [7], or by coronary artery calcification evaluation, as shown in recent work by Rho and colleagues [8].

SAT0398 Diagnostic value of anti mutated citrullinated vimentin in comparison to anti-cyclic citrullinated peptide and anti-viral citrullinated peptide 2 antibodies in rheumatoid arthritis: A multicentric study by firma group

BackgroundIn recent years the diagnostic approach to rheumatoid arthritis (RA) significantly changed. Among new serological assays, an ELISA test detecting antibodies directed against recombinant mutated citrullinated vimentin (anti-MCV), a protein...