Treatment-naive Rheumatoid Arthritis Patients Research Articles

Phosphoproteomic profiling of early rheumatoid arthritis synovium reveals active signalling pathways and differentiates inflammatory pathotypes

BackgroundKinases are intracellular signalling mediators and key to sustaining the inflammatory process in rheumatoid arthritis (RA). Oral inhibitors of Janus Kinase family (JAKs) are widely used in RA, while inhibitors of other kinase families e.g. phosphoinositide 3-kinase (PI3K) are under development. Most current biomarker platforms quantify mRNA/protein levels, but give no direct information on whether proteins are active/inactive. Phosphoproteome analysis has the potential to measure specific enzyme activation status at tissue level.MethodsWe validated the feasibility of phosphoproteome and total proteome analysis on 8 pre-treatment synovial biopsies from treatment-naive RA patients using label-free mass spectrometry, to identify active cell signalling pathways in synovial tissue which might explain failure to respond to RA therapeutics.ResultsDifferential expression analysis and functional enrichment revealed clear separation of phosphoproteome and proteome profiles between lymphoid and myeloid RA pathotypes. Abundance of specific phosphosites was associated with the degree of inflammatory state. The lymphoid pathotype was enriched with lymphoproliferative signalling phosphosites, including Mammalian Target Of Rapamycin (MTOR) signalling, whereas the myeloid pathotype was associated with Mitogen-Activated Protein Kinase (MAPK) and CDK mediated signalling. This analysis also highlighted novel kinases not previously linked to RA, such as Protein Kinase, DNA-Activated, Catalytic Subunit (PRKDC) in the myeloid pathotype. Several phosphosites correlated with clinical features, such as Disease-Activity-Score (DAS)-28, suggesting that phosphosite analysis has potential for identifying novel biomarkers at tissue-level of disease severity and prognosis.ConclusionsSpecific phosphoproteome/proteome signatures delineate RA pathotypes and may have clinical utility for stratifying patients for personalised medicine in RA.

Evaluation of insulin resistance in rheumatoid arthritis in Eastern India

Background: Increase in insulin resistance predisposes to cardiovascular disease. Studies from various parts of world show increase prevalence of IR in rheumatoid arthritis (RA) but there is little data from India. Aims and Objectives: To evaluate the prevalence of IR in RA and after 6 months of treatment with disease-modifying antirheumatic drugs. Materials and Methods: This hospital-based longitudinal observational study was done between July 2018 and June 2019 in the Division of Rheumatology, Department of General Medicine, S.S. Hospital, BHU, in treatment-naive RA patients with age ≥18 years. Exclusion criteria were known diabetes, preexisting dyslipidemias, or any other chronic illness. Detailed history and examination were done. Fasting glucose and fasting insulin were done to calculate the homeostatic model for assessment of IR (HOMA IR). Results: The most common age group in our study was 31–40 years (38%). The mean age of onset of disease was 39.5 years. Female-to-male ratio was 5.25:1. The mean duration of illness was 3 years with baseline mean disease activity score (DAS) 28 score 6.2698 ± 1.07437. Baseline mean cholesterol level, triglyceride, high-density lipoprotein, low-density lipoprotein, and very low-density lipoprotein were 169.40 ± 33.802 mg/dL, 164.42 ± 91.585 mg/dL, 47.66 ± 11.825 mg/dL, 99.88 ± 27.059 mg/dL, and 34.42 ± 19.186 mg/dL, respectively. Baseline fasting blood glucose levels, fasting insulin levels, and HOMA IR were 99.40 ± 20.761 mg/dL, 11.84770 ± 4.351550 m IU/L,and 2.905 ± 1.2272, respectively. After treatment of 6 months, lipid profile, fasting insulin, and HOMA IR improved significantly. However, there was no significant correlation found between IR and disease activity before and after treatment. Conclusion: The patients of RA are at higher risk of IR and dyslipidemia and early diagnosis with the initiation of treatment for RA can reverse the IR in RA patients.

Hydroxychloroquine is neutral on incidental cataracts in patients with rheumatoid arthritis

To study whether hydroxychloroquine (HCQ) therapy increases the risks of cataracts in patients with rheumatoid arthritis (RA). In this retrospective cohort study, 2821 treatment-naive RA patients, collected from the Longitudinal Health Insurance Database, were enrolled from 2000 to 2012 and followed up monthly until secondary cataracts were detected but no later than Dec 31, 2013. All participants were split into two groups according to the usage of HCQ in one year: the HCQ group (465 patients), with a usage duration higher than 90 days, and the non-HCQ group (465 patients), with a usage duration less than 30 days. The HCQ and non-HCQ groups were age-, sex-, complication- and drug combination-matched. There was no significant difference in survival rate between the two groups (p > 0.05). A multivariate logistic regression model was applied. Of all participants, 173 were diagnosed with secondary cataracts in both the HCQ and non-HCQ groups, with 28.8/1000 and 36.5/1000 person-years, respectively. After adjustments for other predictors, patients in the HCQ group had no increased (or decreased/equal) hazard of secondary cataract (hazard ratio (HR): 1.17; confidence interval (CI): 0.86–1.59; p > 0.05). HR analysis of HCQ usage duration, age, sex and corticosteroids showed that the CI of the adjusted HR was not statistically significant. This study showed that HCQ usage was not associated with the risk of cataracts in RA patients.

Adiponectin is negatively associated with disease activity and Sharp score in treatment-na\xefve Han Chinese rheumatoid arthritis patients

The association and potential role of the protein hormone adiponectin in autoimmune diseases causing musculoskeletal disorders, including rheumatoid arthritis (RA), are controversial. Conflicting results may arise from the influences of confounding factors linked to genetic backgrounds, disease stage, disease-modifying anti-rheumatic drugs and patients’ metabolic characteristics. Here, we examined serum level of adiponectin and its relationship with disease activity score 28 with erythrocytes sedimentation rate (DAS28[ESR]) and Sharp score in a treatment-naïve Han Chinese RA population. This cross-sectional study enrolled 125 RA patients. Serum level of total adiponectin was assessed by enzyme-linked immunosorbent assay (ELISA). Other important clinical and laboratory parameters were collected from the hospital database. DAS28(ESR) was calculated according to the equation previously published. Sharp score was evaluated based on hands radiographs by an independent radiologist. The correlation between serum adiponectin level and DAS28(ESR) or the Sharp score was investigated by univariate and multivariable linear regression analyses, respectively. Multiple imputation by chained equations was used to account for missing data. Univariate analyses showed a significant positive correlation between DAS28(ESR) and age or C-reactive protein (CRP) (both p = 0.003), while serum adiponectin level was negatively correlated with DAS28(ESR) (p = 0.015). The negative correlation between adiponectin level and DAS28(ESR) remained true in multivariable analyses adjusted for confounders. In addition, the univariate analyses revealed positive correlations of Sharp score to disease duration (p < 0.001), CRP (p = 0.023) and ESR (p < 0.001). In the multivariable model adjusted for confounders, adiponectin was negatively correlated with Sharp score (p = 0.013). In this single-institution cross-sectional study, serum adiponectin level in treatment-naive RA patients is negatively correlated with DAS28(ESR) and the Sharp score after adjustment for prominent identified confounders. Serum adiponectin may be potentially useful for assessing disease activity and radiographic progression of RA.

Inclusion of Synovial Tissue-Derived Characteristics in a Nomogram for the Prediction of Treatment Response in Treatment-Naive Rheumatoid Arthritis Patients.

ObjectiveThis study applied a synovitis score obtained during routine care from ultrasound (US)–guided biopsies of synovial tissue (ST) in patients with rheumatoid arthritis (RA) and patients with other inflammatory and noninflammatory joint diseases to identify pretreatment synovial biomarkers associated with disease characteristics, and to integrate the findings into a multiparameter nomogram for use in baseline prediction of diagnosis and treatment response in treatment‐naive rheumatoid arthritis (RA) patients.MethodsThe study enrolled a total of 1,015 patients with various autoimmune diseases (545 patients with RA, 167 patients with psoriatic arthritis [PsA], 199 patients with undifferentiated peripheral inflammatory arthritis [UPIA], 18 patients with crystal‐induced arthritis, 26 patients with connective tissue diseases, and 60 patients with osteoarthritis [OA] [as part of the SYNGem cohort]). All patients underwent a US‐guided ST biopsy at baseline, and patients were then stratified according to disease phase. The KSS, along with disease characteristics and clinical outcomes, were incorporated into a nomogram for prediction of achievement of clinical remission in RA patients who were previously naive to treatment. In patients in whom a treat‐to‐target strategy was applied, remission was defined as change in the Disease Activity Score in 28 joints (DAS28) at 6 months after treatment initiation.ResultsThe KSS significantly differed among RA patients, as well as PsA patients and UPIA patients, when compared to OA patients. In RA, the KSS directly correlated with the DAS28 and was related to autoantibody positivity in treatment‐naive RA patients. Moreover, at baseline, treatment‐naive RA patients achieving 6‐month remission according to DAS28 had a lower KSS, shorter duration of symptoms (very early RA [VERA]), and lower disease activity than treatment‐naive RA patients not achieving remission according to DAS28. Results of logistic regression analysis identified the following synergistic predictive factors of achievement of DAS28‐based disease remission at 6 months: having a short disease duration (VERA), not having high disease activity, and having a KSS of <5 at baseline. A nomogram integrating these baseline clinical and histologic characteristics in treatment‐naive RA patients yielded an up to 81.7% probability of achieving 6‐month remission according to the DAS28.ConclusionThe KSS is a reliable tool for synovitis assessment on US‐guided ST biopsy, contingent on the phase of the disease and the autoimmune profile of each patient. This tool could be integrated within a therapeutic response–predictive nomogram for the prediction of treatment response in RA patients who were previously naive to treatment.

Effect of Anti-Rheumatic Treatment on the Periodontal Condition of Rheumatoid Arthritis Patients.

Periodontitis, a bacterial-induced infection of the supporting soft and hard tissues of the teeth (the periodontium), is common in patients with rheumatoid arthritis (RA). As RA and periodontitis underlie common inflammatory pathways, targeting the progression of RA might mediate both periodontitis and RA. On the other hand, patients with RA on immunosuppressive medication have an increased risk of infection. Therefore, the objective of this longitudinal observation study was to assess the effect of methotrexate (MTX) and anti-tumor necrosis factor-α (anti-TNF, etanercept) treatment on the periodontal condition of RA patients. Overall, 14 dentate treatment-naive RA patients starting with MTX and 12 dentate RA patients starting with anti-TNF therapy in addition to MTX were included. Follow-up was scheduled matching the routine protocol for the respective treatments. Prior to the anti-rheumatic treatment with MTX or the anti-TNF therapy in addition to MTX, and during follow-up, i.e., 2 months for MTX, and 3 and 6 months for the anti-TNF therapy in addition to MTX, the periodontal inflamed surface area (PISA) was measured. The efficacy of the anti-rheumatic treatment was assessed by determining the change in RA disease activity (DAS28-ESR). Furthermore, the erythrocyte sedimentation rates were determined and the levels of C-reactive protein, IgM-rheumatoid factor, anti-cyclic citrullinated protein antibodies, and antibodies to the periodontal pathogen Porphyromonas gingivalis, were measured. Subgingival sampling and microbiological characterization of the subgingival microflora was done at baseline. MTX or anti-TNF treatment did not result in an improvement of the periodontal condition, while both treatments significantly improved DAS28 scores (both p < 0.01), and reduced C-reactive protein levels and erythrocyte sedimentation rates (both p < 0.05). It is concluded that anti-rheumatic treatment (MTX and anti-TNF) has negligible influence on the periodontal condition of RA patients.

Metabolic syndrome,hematological markers of inflammation and disease activity in rheumatoid arthritis

Background: The coexistence of Rheumatoid Arthritis (RA) and Metabolic Syndrome (MetS) is common. Aim: The present study assessed the effect of MetS on disease activity and hematological markers of inflammation to Platelets/Lymphocyte Ratio (PLR) and Neutrophil/Lymphocyte Ratio (NLR) in RA patients. Study design: A cross-sectional case control study using STARD reporting guideline. Methods: The present study included 5 groups: treatment-naive RA patients with MetS (GI, n=50), treated RA patients with MetS (GII, n=50), treatment-naive RA patients without MetS (GIII, n=50), treated RA patients without MetS (GIV, n=50) and healthy age and sex-matched controls (GV, n=50). RA was diagnosed based on the 2010 ACR/EULAR criteria. Disease activity of RA patients was calculated using the DAS-28 score. For the diagnosis of MetS, we adopted the Harmonized Joint Scientific Statement (HJSS) on metabolic syndrome recommendations. Results: Patients in GI had significantly higher DAS28 when compared with other groups. GII and GIII patients had significantly higher DAS28 when compared with GIV. It was also shown that GI patients had significantly higher PLR and NLR when compared with GIII. Similarly, GII patients had significantly higher PLR and NLR when compared with GIV. Logistic regression analysis identified presence only MetS [OR (95%CI): 8.66 (1.34-56.1), p=0.024] and increased PLR (OR (95%CI): 0.98 (0.96-0.99), p=0.002) as independent predictors of high disease activity in treatment-naive patients while increased PLR was the only independent predictor of disease activity in treatmentexperienced patients. Conclusion: Metabolic syndrome is associated with elevated hematological markers of inflammation and disease activity in treatment-naive RA patients. Both PLR and NLR are risk factors for RA activity in treatment-naive patients with PLR being more strongly correlated with disease activity.

Disease severity affects myocardial functions in patients with treatment-naive early rheumatoid arthritis.

The cross-sectional study aimed to assess myocardial functions using global longitudinal strain (GLS) echocardiography and arrhythmia parameters with treatment naive newly diagnosed rheumatoid arthritis (RA) and no clinical evidence of cardiovascular disease (CVD). Seventy seven newly diagnosed treatment-naive RA patients were enrolled. Disease severity was evaluated according to rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPA) positivity, and Disease Activity Score 28 C-reactive protein (DAS28 CRP). Myocardial functions were assessed using conventional echocardiography and GLS technique and electrocardiogram parameters cQT and Tp-e/cQT. Twenty three patients had severe disease while 54 patients were non-severe. The Left Ventricle GLS (17.98±1.24 vs 21.29±1.03, P<.001), cQT (428.71±9.05 vs 394.61±17.83, P<.001), Tp-e/cQT (0.19±0.02 vs 0.16±0.01, P<.001) for severe RA patients was reduced compared to RA non-severe patients. Penalized maximum likelihood estimation logistic regression analysis revealed LVGLS as the only significantly independent predictor of severe RA disease (OR 0.70, CI 95% 0.52-0.92, P=.001). Receiver operating characteristic (ROC) curves of the LVGLS was revealed 19.9 as GLS discriminative value with 88.8% positive predictive value for predicting severity. Severe RA risk increases when log-odds value was over 0, corresponds to LVGLS value less than 18 by partial effect plots. RA severity was associated with lower LV systolic myocardial function and increased arrhythmia parameters. Only LVGLS was significantly independent predictor of RA disease severity.

Cost-effective analysis of disease-modifying anti-rheumatic drugs in rheumatoid arthritis.

The main objective of the study was to perform the pharmacoeconomic analysis of synthetic disease-modifying anti-rheumatic drugs in rheumatoid arthritis patients. A prospective, observational study was conducted in 98 rheumatoid arthritis (RA) patients meeting 2010 Rheumatoid Arthritis Classification Criteria. Treatment-naive RA patients were initiated on synthetic disease-modifying anti-rheumatic drugs (DMARD/s) and followed up for 3months. Average cost-effectiveness analysis was done by taking Health Assessment Questionnaire Disability Index (HAQ-DI) score as a measure of effectiveness. Out of the 98 RA patients, 15.30% were males and 84.69% females. 80.61% RA patients are seropositive. Majority of the study population patients (55%) were on combination of three synthetic DMARDs and almost a quarter (24.48%) were on combination of two synthetic DMARDs. The mean value of DAS 28 at baseline was 6.07±1.33 and after 3months treatment, the mean was 3.84±1.11. The mean disability index measured by HAQ-DI was significantly reduced from 1.43±0.71 to 0.81±0.61, p<0.001, after 3months treatment. The direct medical cost of treatment of RA per month is 997.05 rupees. The average cost-effectiveness ratio of combination of synthetic DMARDs was 1533.92 rupees. Treatment of RA with synthetic DMARDs controls disease activity and improves disability with reasonable cost of treatment. The majority of the direct medical cost is attributable to cost of medicine and laboratory investigation. Use of quality generic drugs and an early diagnosis would minimize the economic burden on the patient.

Left ventricular function at two-year follow-up in treatment-naive rheumatoid arthritis patients is associated with anti-cyclic citrullinated peptide antibody status: a cohort study

Objectives: In rheumatoid arthritis (RA), the role of autoimmunity, especially anti-cyclic citrullinated peptide antibody (anti-CCP) level, and the time-course of left ventricular (LV) function is unknown. The objective was to assess LV function and the amount of coronary calcium in relation to anti-CCP levels in a cohort of treatment-naive RA patients, and to assess changes in these parameters during a 2 year follow-up period.Method: Sixty-six steroid- and disease-modifying anti-rheumatic drug-naive RA patients were treated with methotrexate according to the Danish national guidelines. We assessed LV function by conventional echocardiography and speckle-tracking echocardiography. We estimated the amount and progression of coronary calcium by coronary computed tomography. Patients were examined at the time of diagnosis and after 2 years.Results: Patients with elevated anti-CCP at baseline and after 2 years, compared to those with non-persistently elevated anti-CCP, had significantly less improvement in S´ (1 ± 1.4 cm/s vs 0.2 ± 0.9 cm/s; p = 0.04) and a worsening in global longitudinal systolic strain (GLS) (0.6 ± 1.8% vs −1 ± 2.8%; p = 0.04). There was a significant correlation between ΔGLS over 2 years and anti-CCP at 2 year follow-up (r = 0.36; p = 0.006). We observed a small progression of coronary calcium score during the 2 year follow-up period. No differences in progression were found between patients with high anti-CCP titres at baseline and 2 year follow-up (n = 12) and patients with normal/low anti-CCP titres (n = 32) (23.8 ± 40.3 vs 22.6 ± 68.9; p = 0.96).Conclusions: Deformation analysis by speckle-tracking echocardiography is a valuable tool to detect early development of myocardial dysfunction despite normal ejection fraction in RA.

Regulatory CD4+ T-Cell Subsets and Anti-Citrullinated Protein Antibody Repertoire: Potential Biomarkers for Arthritis Development in Seropositive Arthralgia Patients?

ObjectiveSeropositive arthralgia patients (SAP) are at high risk of developing rheumatoid arthritis (RA). This prospective study aimed to determine whether altered peripheral regulatory T-cells (Tregs) and defined subsets, besides a broadened anti-citrullinated protein antibody (ACPA) response, may qualify as biomarkers for RA development in SAP.MethodsThirty-four consecutive SAP were prospectively assessed every 6 months for minimally 2 years. At inclusion, peripheral Treg (CD4+CD25+FoxP3+) numbers and subsets, defined as CD45RA+FoxP3low naive Tregs (Fr I), CD45RA-FoxP3high activated Tregs (Fr II) and CD45RA-FoxP3low non-Tregs (Fr III), were compared to age- and sex-matched healthy controls (HC, n = 16) and treatment-naive RA patients (n = 12). SAP that developed RA were compared to non-switchers and analyzed for Treg numbers and Treg subsets at inclusion. Also, Treg numbers and subsets were compared in switched SAP before and at diagnosis. To assess the ACPA repertoire, IgG and IgA reactivity was measured against citrullinated peptides from fibrinogen, α-enolase and vimentin.ResultsTreg numbers were similar between HC, SAP and RA patients. Although the bonafide Treg subsets Fr I and Fr II were comparable between groups, Fr III was increased in SAP compared to HC (p = 0.01). Fourteen (41%) SAP developed RA during follow-up. Their Treg numbers and subsets were comparable to non-switched SAP. At RA diagnosis, Treg numbers in switched SAP were similar to 6 months before. Switched SAP displayed a more diverse IgG ACPA repertoire compared to non-switched SAP (p = 0.046) and showed more IgA reactivity than non-switched SAP reaching significance for Fib1 only (p = 0.047).ConclusionNumbers of Total Treg and bonafide Treg subsets are not indicative for RA development in SAP, opposed to the ACPA repertoire.

10 Quantitative myocardial perfusion and longitudinal strain by feature tracking in newly diagnosed, treatment naïve rheumatoid arthritis

Objectives Rheumatoid arthritis (RA) is associated with increased cardiovascular mortality. Proposed mechanisms include coronary microvascular dysfunction due to immune dysregulation and systemic inflammation. First pass myocardial perfusion CMR allows quantification of myocardial blood flow (MBF) and myocardial perfusion reserve (MPR). In the absence of coronary artery disease (CAD), reduced MPR represents coronary microvascular dysfunction. We hypothesised MPR would be reduced in RA and that abnormalities in left ventricular (LV) deformation would be evident in RA, as LV mass has been reported to be reduced in established disease. Methods Twelve patients with newly diagnosed, treatment naive RA and 12 healthy volunteers (HV) underwent CMR at 3.0T (Phillips Achieva TX). Both groups had no history of CAD. Dual bolus resting and stress perfusion imaging was performed (0.1mmol/kg Gadolinium DTPA) and MBF estimated for the mid ventricular slice using Fermi constrained convolution (PMI v 0.4 [Sourbron, 2009]). Left ventricular ejection fraction (LVEF) and global longitudinal strain (GLS) by feature tracking were calculated using bSSFP images (CVI 42 , Circle Cardiovascular Imaging, Calgary, Canada). Results Mean age of RA patients was 48 ± 16 and mean age of HV 47 ± 14. Of the RA patients, 4 were male and 8 female. Of the HV, 2 were male and 10 female. Mean MPR values were 1.98 ± 0.79 and 1.99 ± 0.72 (P = 0.88) for RA and HV respectively (Figure 1). Mean values for LVEF were 63 ± 4 and 62 ± 4% (P = 0.48) respectively for RA patients and HV. Mean values for GLS were −20.2 and −21 ± 0.4 (P = 0.396) for RA and HV respectively. Conclusion These findings suggest treatment naive RA patients have no detectable abnormalities on perfusion CMR. Therefore, whilst present in established RA, coronary microvascular dysfunction may not yet have developed in early RA. No abnormalities of LV systolic function were evident and may be a later manifestation of RA.

Abstract 10336: Left Ventricular Deformation at 2-year Follow-up in Treatment-naive Rheumatoid Arthritis Patients is Associated With High Inflammation Parameters: A Open Cohort Study

Introduction: Patients with rheumatoid arthritis (RA) are at increased risk of cardiovascular disease (CVD). The role of autoimmunity and especially citrullination in the pathogenesis of the increased risk of CVD and the time-course of left ventricular (LV) dysfunction are unknown. Hypothesis: To assess LV function by speckle-tracking echocardiography and the amount of coronary calcium by coronary computer tomography (CCT) in relation to anti-cyclic citrullinated peptide antibody (anti-CCP) status during a 2-year follow-up period in a open cohort of treatment-naive RA patients. Methods: Thirty-nine treatment-naive early RA patients (21 women) were included at time of diagnosis and followed for 2 years. Disease activity, IgM rheumatoid factor (IgM-RF) and anti-CCP was assessed at time of diagnosis and at 2-year follow-up. We assessed both the LV deformation by speckle-tracking echocardiography whereby we measured global longitudinal systolic strain (GLS) and coronary calcium score (Agatston′s score) by coronary computer tomography (CCT) at time of diagnosis and at 2-year follow-up. Results: We found GLS similar at baseline and after 2-year follow-up (GLSBASELINE: -16.56±3.1% vs. GLS2-YEAR: -16.27±2.8%; p=0.66). However, in patients with anti-CCP ≥340 at baseline and patients who persistently had an anti-CCP ≥340 at 2-year follow-up (n=10), we observed a significant decrease in deformation compared to patients who did not (n=29); (2.9±3.2% vs. -0.6±2.7%; p=0.002). Furthermore, we observed a significant association between the changes in GLS over 2 years (GLSDELTA: 0.27±3.21%) and anti-CCP (r=0.63; p&lt;0.0001), which remained significantly associated (p&lt;0.0001) after correction for relevant confounders. No significant progression in coronary calcium score was observed in the observation period. Conclusions: LV deformation is reduced in treatment-naive RA patients with persistently elevated anti-CCP and deformation abnormalities is associated with the degree of anti-CCP positivity in a 2-year follow-up period. Our observations make deformation analysis by speckle-tracking echocardiography a strong tool to detect early development of myocardial dysfunction in treatment naive RA.

85 Newly Diagnosed, Treatment-Naive Patients with Rheumatoid Arthritis have early Abnormalities of Vascular and Myocardial Function

Background Rheumatoid arthritis (RA) is a common autoimmune disease. Mortality is increased compared to the general population largely due to increased cardiovascular disease (CVD). Immune dysregulation and systemic inflammation are thought to be associated with this increased risk. CMR can provide an assessment of CVD, including myocardial and vascular morphology and function, but it is unknown which CMR measurements are most sensitive to detect early CVD. Objectives To determine CV manifestations of RA using CMR in newly diagnosed, treatment-naive patients compared with matched controls. Method Fifty-two RA patients fulfilling ACR/EULAR classification RA criteria, without CVD history, underwent CMR at 3.0T (Philips Achieva TX). They had symptoms for less than 1 year, had not yet received therapy with any disease modifying anti-rheumatic drugs, disease activity score (DAS28) ≥ 3.2 and at least one RA poor prognostic factor. 30 healthy controls were matched by age, sex and blood pressure. Standard balanced steady state free precession (SSFP) cine images were acquired and LV dimensions calculated. Strain analysis was performed by tissue-tagging using a spatial modulation of magnetization pulse sequence. For aortic distensibility (AD), multi-phase SSFP cine images (50 phases) were acquired in a plane transverse to the ascending aorta at the level of the pulmonary artery bifurcation. Aortic contours were drawn by manual planimetry of the endovascular–blood pool interface at the times of minimal and maximal distension. Native and 15 min post-contrast T1 maps were generated from mid-LV short axis using a modified 3,3,5 Look-Locker inversion sequence to calculate extra-cellular volume fraction (ECV). Results Participant characteristics are presented in Table 1. Aortic distensibility was reduced in RA patients compared to controls (mean±SD, 3.23 ± 1.6 10–3 mmHg-1 vs. 4.99 ± 1.8 10–3 mmHg-1, p = 0.001). Other measures of arterial stiffness including aortic stiffness index, compliance and strain showed differences with similar significance levels. Left ventricular remodelling was not different in the RA group compared with controls, but S’ was lower in RA (mean±SD, 0.99 ± 0.22 Seconds-1 vs. 1.13 ± 0.16 Seconds-1, p = 0.007) which may signify sub-clinical reduction in myocardial performance. Evidence for overt inflammation/fibrosis was seen in 4 patients with areas of focal non-ischaemic patterns of LGE, but native T1 and ECV was not different between the groups. See Table 2. Conclusion Early abnormal subclinical changes in vascular and myocardial function exist in newly diagnosed, treatment-naive RA patients, without overt changes in ventricular performance and geometry. The natural history of these observations and implications in the wider management of RA warrant further investigation.

Newly diagnosed, treatment-naive patients with rheumatoid arthritis have early abnormalities of vascular and myocardial function

Background Rheumatoid arthritis (RA) is a common autoimmune disease. Mortality is increased compared to the general population largely due to increased cardiovascular disease (CVD). Immune dysregulation and systemic inflammation are thought to be associated with this increased risk. CMR can provide an assessment of CVD, including myocardial and vascular morphology and function, but it is unknown which CMR measurements are most sensitive to detect early CVD. Objectives To determine CV manifestations of RA using CMR in newly diagnosed, treatment-naive patients compared with matched controls. Method Fifty-two RA patients fulfilling ACR/EULAR classification RA criteria, without CVD history, underwent CMR at 3.0T (Philips Achieva TX). They had symptoms for less than 1 year, had not yet received therapy with any disease modifying anti-rheumatic drugs, disease activity score (DAS28) ≥ 3.2 and at least one RA poor prognostic factor. 30 healthy controls were matched by age, sex and blood pressure. Standard balanced steady state free precession (SSFP) cine images were acquired and LV dimensions calculated. Strain analysis was performed by tissue-tagging using a spatial modulation of magnetization pulse sequence. For aortic distensibility (AD), multi-phase SSFP cine images (50 phases) were acquired in a plane transverse to the ascending aorta at the level of the pulmonary artery bifurcation. Aortic contours were drawn by manual planimetry of the endovascular–blood pool interface at the times of minimal and maximal distension. Native and 15 min post-contrast T1 maps were generated from mid-LV short axis using a modified 3,3,5 Look-Locker inversion sequence to calculate extra-cellular volume fraction (ECV). Results Participant characteristics are presented in Table 1. Aortic distensibility was reduced in RA patients compared to controls (mean±SD, 3.23 ± 1.6 10–3 mmHg-1 vs. 4.99 ± 1.8 10–3 mmHg-1, p = 0.001). Other measures of arterial stiffness including aortic stiffness index, compliance and strain showed differences with similar significance levels. Left ventricular remodelling was not different in the RA group compared with controls, but S’ was lower in RA (mean±SD, 0.99 ± 0.22 Seconds-1 vs. 1.13 ± 0.16 Seconds-1, p = 0.007) which may signify sub-clinical reduction in myocardial performance. Evidence for overt inflammation/fibrosis was seen in 4 patients with areas of focal non-ischaemic patterns of LGE, but native T1 and ECV was not different between the groups. See Table 2. Conclusion Early abnormal subclinical changes in vascular and myocardial function exist in newly diagnosed, treatment-naive RA patients, without overt changes in ventricular performance and geometry. The natural history of these observations and implications in the wider management of RA warrant further investigation.

Remission induction comparing infliximab and high-dose intravenous steroid, followed by treat-to-target: a double-blind, randomised, controlled trial in new-onset, treatment-naive, rheumatoid arthritis (the IDEA study)

ObjectivesIn disease modifying antirheumatic drug (DMARD)-naive early rheumatoid arthritis (RA), to compare the efficacy of methotrexate (MTX) and infliximab (IFX) with MTX and intravenous corticosteroid for remission induction.MethodsIn a 78-week...

Differentially Expressed Epigenome Modifiers, Including Aurora Kinases A and B, in Immune Cells in Rheumatoid Arthritis in Humans and Mouse Models

To identify epigenetic factors that are implicated in the pathogenesis of rheumatoid arthritis (RA), and to explore the therapeutic potential of the targeted inhibition of these factors. Polymerase chain reaction (PCR) arrays were used to investigate the expression profile of genes that encode key epigenetic regulator enzymes. Mononuclear cells from RA patients and mice were monitored for gene expression changes, in association with arthritis development in murine models of RA. Selected genes were further characterized by quantitative reverse transcription-PCR, Western blot, and flow cytometry methods. The targeted inhibition of the up-regulated enzymes was studied in arthritic mice. A set of genes with arthritis-specific expression was identified by the PCR arrays. Aurora kinases A and B, both of which were highly expressed in arthritic mice and treatment-naive RA patients, were selected for detailed analysis. Elevated aurora kinase expression was accompanied by increased phosphorylation of histone H3, which promotes proliferation of T lymphocytes. Treatment with VX-680, a pan-aurora kinase inhibitor, promoted B cell apoptosis, provided significant protection against disease onset, and attenuated inflammatory reactions in arthritic mice. Arthritis development is accompanied by changes in expression of a number of epigenome-modifying enzymes. Drug-induced down-regulation of the aurora kinases, among other targets, seems to be sufficient to treat experimental arthritis. Development of new therapeutics that target aurora kinases can potentially improve RA management.

FRI0199 Usefulness of matrix metalloproteinase-3 as a predictor of total knee arthroplasty in patients with rheumatoid arthritis

BackgroundThe main goal of rheumatoid arthritis (RA) treatment is to maximize the patient’s long-term QOL. In addition to achievement/maintenance of clinical remission, prevention of structural change such as joint destruction...