Rheumatoid Arthritis Pts Research Articles

Left ventricular morphology and function in rheumatoid arthritis patients without cardiac symptoms, using a cardiac magnetic resonance imaging

Background Patients with rheumatoid arthritis (RA) experience an excess risk of congestive heart failure (CHF), chronic inflammation plays a pivotal role in this increased risk. Despite the growing body of research on cardiovascular (CV) disease in RA, the key pathways underlying the development of abnormalities in myocardial structure and function associated with CHF remain obscure. Cardiac magnetic resonance imaging (CMR) has been used to identify early functional and structural changes in the left ventricle (LV) before development of clinically overt CHF. We evaluated LV function and structure using a CMR in RA patients (pts) without cardiac symptoms, and determined the impact of non-biologic DMARDs and biologic DMARDs. Methods Consecutive RA pts and healthy control were enrolled. RA pts received biologic DMARDs (bDMARDs) or non-biologic DMARDs (nbDMARDs). All subjects underwent evaluation of LV function and structure using non-contrast CMR. LV function was based on LV ejection fraction (EF), end-systolic volume (ESV), end-diastolic volume (EDV), stroke volume (SV), and cardiac output (CO). LV hypertrophy was measured by absolute LV mass (LVM) and LV mass index (LVMI) determined by LVM/body surface area. Subjects were classified into four categories based on LVMI and LVM/EDV of control subjects, with the mean + 2 SD of each measure defined as elevated LVMI and LVM/EDV. Results We compared 90 female RA pts (mean age, 55.9±7.1 years) with a matched 20-patient control group (mean age, 52.7±4.6 years). 46 RA pts received nbDMARDs [43, methotrexate (MTX); 3, other drugs)] and 44 RA pts received bDMARDs [(18, infliximab; 26, tocilizumab) plus MTX]. The Simplified Disease Activity Index (SDAI) was significantly higher in the nbDMARDs group than in the bDMARDs group (p=0.002). Compared to the control group, the nbDMARDs group showed significantly higher LVMI and lower EF (p 1.02 (2) concentric hypertrophy (LVMI>66.9 and LVM/EDV>1.02 (3) eccentric hypertrophy (LVMI>66.9 and LVM/EDV <1.02 and (4) normal geometry (LVMI<66.9 and LVM/EDV<1.02. Among those with abnormal LV geometry, 32% of RA patients in the nbDMARDs group showed eccentric hypertrophy. 98% of RA patients in the bDMARDs group showed normal geometry. LVMI and EF were significantly associated with SDAI (r=0.567, p<0.001; r=0.412, p=0.02, respectively). Mass/EDV tended to be associated with SDAI (p=0.07). Adjustment for ESR did not modify the association of SDAI with EF and LVMI (p=0.017, p=0.005, respectively). Conclusions Biologics treatment may reduce progression of subclinical LV dysfunction and normalize LV structure in association with the reduction in disease activity. It can be presumed that active RA may be an important contributor to the development of myocardial abnormalities.

Survival Improvement in Myelodysplastic Syndrome with Refractory Anemia after Treatment with Selective-Serotonin-Reuptake-Inhibitors

Background : Low riskMyelodysplastic Syndrome (LR-MDS) is a cytogenetic, epigenetic and immunologically heterogeneous group of disorders associated with refractory anemia (RA) in about 75% of the cases. Conventionally, blood transfusion and Erythropoiesis Stimulating Agents (ESAs) are indicated. Azanucleosides provide clinical benefit in about 20-25% of patients (pts) with ESA refractory disease highlighting the need for new drug development. Chronic inflammation derived from deregulated cytokines with myelosupressive potential, ( IL6, TNF-ɑ and INF-λ) is an important factor in LR-MDS. Selective-Serotonin-Reuptake-Inhibitors (SSRIs) provide clinical benefit in depressed and rheumatoid arthritis pts, at least in part by stabilizing TNF-ɑ and IL6 levels (Brunoni AR., et al. Ann Rev of Med. 2013). In colon and prostate cell lines SSRIs inhibit proliferation. This data suggests that SSRIs may act in at least two ways that would be beneficial in MDS. Here we investigate clinical benefit of SSRIs in treating a subgroup of MDS patients with refractory anemia (RA-MDS).Methods: One hundred and twenty patients over the age of 18-diagnosed with MDS were identified in the Michael E. DeBakey VA Medical Center cancer registry between January 1, 2000 to December 31 2012. Of these, 55 LR-MDS pts with anemia were identified. Patients were considered to be SSRI+ if they had received at least 6 months of a SSRI (including fluoxetine, sertraline, paroxetine or citalopram) in the 12 months preceding or following the diagnosis of MDS. Overall Survival for the SSRI+ and SSRI- groups were estimated by the Kaplan-Meier method. Multivariate Cox regression analysis was performed to assess the impact of multiple independent variables on clinical outcomeResults: Among the 55 patients studied, 8 and 47 belonged to SSRI+ and SSRI- groups, respectively. Mean age in the SSRI+ group was 69.5 years (median 72, range 55 to 82) and in the SSRI- group was 74.2 years (median 75, rangе 53 to 88); P=0.252. WHO 2008 classification for SSRI+ group was RUCD 3 [37.5%] and RCMD 5 [61.5%]; For the SSRI- group the classification was RUCD 13 [27.7%]; RCMD 30[63.8%]; RAEB 2[4.3]; MDS MPN unclassified 1[2.1%] and MDS 5q- 1[2.1%]. Median hemoglobin (Hb) level in the SSRI+ group was 10.5 g/dL (8-12 g/dL) and in the SSRI- group was 8.9 g/dL (range, 6-13), P=0.027. Given the central interest of anemia impact on Overall Survival (OS), adjustment for heterogeneity in Hb levels among SSRI+ and SSRI- groups was performed using subgroup survival analysis in pts with equivalent Hb levels (pts with Hb<8 were excluded resulting in P=0.067). Median OS was 62 months (range, 15.3-73.7) for the SSRI+ group (N=8) and 27.5 months (range, 15.7-39.3) for SSRI- pts (N=34) (P=0.0323, HR=3.045, 95% CI=[1.155,8.028]) (Fig. 1). Blast count, cytogenetic group and R-IPSS score did not impact OS on univariate or multivariate analysis.Conclusions: Improved survival of LR-MDS anemic pts is central to treatment paradigms of MDS. Our study suggests survival improvement in LR- MDS pts treated with SSRIs. Potential clinical beneficial effect of SSRIs could be restricted to LR-MDS pts presenting with anemia. Prospective studies aimed at investigating molecular mechanisms of action, potential overall response rate as single agents or in combination with other MDS directed therapy are needed. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

FRI0097 Factors Associated with Major Depressive Disorder in Rheumatoid Arthritis Patients

BackgroundPsychiatric disorders occur in rheumatoid arthritis (RA) patients very often. It is considered that major depressive disorder (MDD) in RA is stress-related and associated with disease activity and chronic pain.Objectivesto...

THU0171 Which Adverse Events (AES) of Biological Therapy (BT) Led to Discontinuation of Treatment in A Cohort of 377 JIA Patients in Comparison to 1115 Patients Affected by Ra, As, PSA in the Department of Rheumatology of G. Pini Institute

ObjectivesTo report adverse events (AEs), which led to discontinuation of biologics agents, in a large cohort of patients with Juvenile Idiopathic Arthritis (JIA), Rheumatoid Arthritis (RA), Ankylosing Spondylitis (AS) and...

FRI0035 Prediction of TNF Inhibitor Response in Rheumatoid Arthritis Patients Using Single Cell Network Profiling of Intracellular Immune Signaling

BackgroundBiomarkers predictive of drug efficacy are lacking in rheumatoid arthritis (RA) and would be useful in clinical practice and clinical trials. Single cell network profiling (SCNP) is a multiparametric flow...

THU0157 Comparison of Clinical Outcomes between Rheumatoid Arthritis Patients under TNF Inhibitors Using A Tapering Strategy or Standard Therapy Regimen in Daily Clinical Practice

BackgroundThere is sparse evidence about the disease control after longterm tapering of TNF inhibitors (TNFi)in rheumatoid arthritis (RA)patients (pts)ObjectivesTo compare the clinical outcomes in RA pts on tapering strategy with...

FRI0298 The Impact of DMARD Co-Therapy on Abatacept Effectiveness in Rheumatoid Arthritis Patients. A Pan-European Analysis of RA Registries

BackgroundBiological disease-modifying anti-rheumatic drugs (bioDMARDs) are generally used in combination with conventional synthetic DMARDs (csDMARDs) in the treatment of rheumatoid arthritis (RA). Anti-TNF agents are more effective in combination with...

SAT0134 Prevalence of Cardiovascular Risk Factors and Cardiovascular Disease in Rheumatoid Arthritis Patients across International Regions: A Comparison of the Corrona International and Corrona US Registries

BackgroundCardiovascular disease (CVD) is a major comorbidity in patients (pts) with rheumatoid arthritis (RA). We explored variations in the prevalence of cardiovascular (CV) risk factors and CVD among RA pts...

AB0240 DAS28(CRP)

BackgroundTreatment to lowest disease activity possible is the recommended treatment target for patients (pts) with rheumatoid arthritis (RA). However, radiographic damage and inflammatory biomarkers may differ based on treatment received...

FRI0052 Variations in Disease Activity and Therapeutic Management of Rheumatoid Arthritis in Different International Regions: A Comparison of Data from the Corrona International and Corrona US Registries

BackgroundThe CORRONA International (C.Intl) rheumatoid arthritis (RA) registry is a multinational RA registry uniformly collecting baseline and longitudinal data. We explored variations in RA disease activity and drug utilization across...

OP0165 Changes in Lipoprotein(A) after Treatment with Tocilizumab (TCZ), Adalimumab (ADA), and Methotrexate (MTX) in Patients with Rheumatoid Arthritis (RA)

BackgroundClinical and epidemiological evidence implicates elevated lipoprotein (a) [Lp(a)] level as a risk factor for cardiovascular disease (CVD).1 Lp(a) is also implicated as a causal agent in the atherothrombotic process.1...

FRI0335 Serum Levels of Immunoglobulins and Free Light Chains in Patients with Rheumatoid Arthritis Treated with Abatacept

BackgroundThrough costimulation blockade, Abatacept (ABA) may down-modulate the immune responses of B lymphocytes in Rheumatoid Arthritis (RA). We previously showed that ABA reduces the serum levels of different classes of...

THU0147 Tofacitinib, an Oral Janus Kinase Inhibitor: Analysis of Malignancies across the Rheumatoid Arthritis Clinical Programme

BackgroundTofacitinib is a novel, oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA).ObjectivesAn evaluation of malignancies in the tofacitinib RA programme from the Phase (P) 2, P3, and...

THU0126 Evaluation of the Effect of Tofacitinib on Measured Glomerular Filtration Rate in Patients with Active Rheumatoid Arthritis

BackgroundIn the clinical development programme of the novel oral Janus kinase inhibitor tofacitinib for the treatment of rheumatoid arthritis (RA), small mean increases in serum creatinine (SCr) (<4 μmol/L least...

THU0315 Increasing Proportion of Concomitant Fibromyalgia in Rheumatoid Arthritis Cohort Corresponds to Growing Arthritis Activity Assessed by Composite Indices

BackgroundFibromyalgia (FM) is well described as a concomitant syndrome that can frequently accompany connective tissue diseases, especially rheumatoid arthritis (RA). In this epoch of modern biologic therapy and RA tight...

OP0154 Integrated Safety Analysis of Tofacitinib in RA Clinical Trials with A Cumulative Exposure of 12,664 Patient-Years

BackgroundTofacitinib is an oral Janus kinase (JAK) inhibitor for the treatment of rheumatoid arthritis (RA). Phase (P) 2, P3, and open-label long-term extension (LTE) studies described the safety profile of...

AB0461 Effect of Methotrexate and Glucocorticoids Therapy on Cardiovascular Disease in Patients with Rheumatoid Arthritis

BackgroundThe risk of cardiovascular disease (CVD) is increased in patients (pts) with rheumatoid arthritis (RA). Systemic inflammation and therapy influence the risk of CVD. Immunosuppressive medications may demonstrate both positive...

AB0471 Efficacy and Tolerability of A Homeopathic Medication Incena in Patients with Rheumatoid Arthritis (Randomized, Double-Blind, Placebo-Controlled Study)

BackgroundSymptomatic therapy of rheumatoid arthritis (RA) such as non-steroidal anti-inflammatory medications (NSAIDs) can be accompanied by serious side effects.Objectivesto assess anti-inflammatory, analgesic, immunomodulatory action and tolerability of Incena as an...

THU0149 Efficacy and Safety of Baricitinib in Japanese Rheumatoid Arthritis Patients at 12 Weeks

BackgroundBaricitinib, a novel, oral inhibitor of JAK1/JAK2 in the JAK-STAT signaling pathway, was evaluated in a blinded Phase 2b study in Japanese patients (pts) with rheumatoid arthritis (RA) with an...

FRI0300 Baseline Characteristics and Pattern of TOCILIZUMAB Use in Patients with Rheumatoid Arthritis: Interim Results from the Multinational, Observational ACT-UP Study

BackgroundTocilizumab (TCZ), an IL-6 receptor inhibitor, has been approved in combination with disease-modifying antirheumatic drugs (DMARDs) or as monotherapy for the treatment of adults with rheumatoid arthritis (RA).1 ACT-UP is...