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ID PMID Title PublicationDate abstract
23869169 Current perspectives on tocilizumab for the treatment of rheumatoid arthritis: a review. 2013 Rheumatoid arthritis (RA) remains a major clinical problem with many patients having continuing systemic inflammatory disease resulting in progressive erosive damage and high levels of disability. A range of pro-inflammatory cytokines including tumor necrosis factor (TNF), interleukin (IL)-1 and IL-6 are involved in RA pathogenesis; these cytokines can be specifically inhibited by biological agents. Tocilizumab (TCZ) is a recombinant humanized anti-IL-6 receptor monoclonal antibody, administered monthly by intravenous infusion that prevents IL-6 signal transduction. There is strong evidence that it is both clinically efficacious and cost-effective. There have been several key clinical trials evaluating the safety and efficacy of TCZ in RA patients. We review five Phase II trials and seven Phase III trials enrolling a total of 626 and 5268 RA patients respectively. The American College of Rheumatology (ACR) response criteria were used as the primary or secondary outcome measure in all trials. Overall these trials demonstrated that TCZ was effective in the treatment of RA in a number of patient groups, including those with an inadequate response to methotrexate (MTX) or TNF inhibition. TCZ use, both as monotherapy and in combination with MTX, improved the signs and symptoms of RA within several weeks of commencing treatment. Additionally, TCZ was shown to reduce radiological disease progression and improve physical function, both as monotherapy and in combination with MTX. A 5-year extension study demonstrated that TCZ sustained good long-term efficacy and safety profiles. TCZ was generally well tolerated. Although its use increased the risk of an adverse event, these were usually mild to moderate in severity and treatment did not increase the risk of a serious adverse event in comparison to controls. Due to moderate increases in serum levels of total cholesterol, triglycerides, high-density lipoproteins and serum transaminases seen in those patients treated with TCZ, as well as severe neutropenia in some, regular blood monitoring of full blood count, liver function and lipids is recommended. Given its clinical efficacy in the treatment of RA, TCZ may be beneficial in the treatment of other autoimmune diseases where IL-6 plays a role in the inflammatory cascade.
23844933 Comparison of intracellular methotrexate kinetics in red blood cells with the kinetics in 2014 Mar AIM: To assess the similarities in intracellular pharmacokinetics (PK) of methotrexate (MTX) in red blood cells (RBCs) and other cell lines. METHODS: Three previously published PK models for intracellular MTX and MTX polyglutamate (MTXGlu2-5 ) concentrations were used: (i) a model for the kinetics in RBCs, (ii) a model for the kinetics in human breast cancer cells (HBCCs) and (iii) a model for the kinetics in various white blood cell (WBC) lines. All three models were used to simulate the response in a typical individual receiving 10 mg oral MTX once weekly and the predicted steady-state concentrations (Css ) and time to Css (tss ) were compared. RESULTS: The HBCC model showed a lower Css for MTXGlu2 and 3 and higher Css for MTXGlu4 and 5 compared with the RBC PK model, while tss and overall intracellular MTX exposure appeared similar. The WBC PK model showed much lower Css for the parent MTXGlu1 and of tss for all MTXGlun , as well as a much lower cumulative Css for MTXGlu2-7 for the majority of the WBC cell lines. CONCLUSION: RBC kinetics of MTX differ from the kinetics in other cell types such as WBCs and HBCCs to a variable degree. It is possible that similarly diverse profiles may exist across other cell lines, including those on the causal path in rheumatoid arthritis. Hence, there may not necessarily be a clear link between RBC MTX concentrations and disease control in rheumatoid arthritis.
24711809 The dopaminergic system in autoimmune diseases. 2014 Bidirectional interactions between the immune and the nervous systems are of considerable interest both for deciphering their functioning and for designing novel therapeutic strategies. The past decade has brought a burst of insights into the molecular mechanisms involved in neuroimmune communications mediated by dopamine. Studies of dendritic cells (DCs) revealed that they express the whole machinery to synthesize and store dopamine, which may act in an autocrine manner to stimulate dopamine receptors (DARs). Depending on specific DARs stimulated on DCs and T cells, dopamine may differentially favor CD4(+) T cell differentiation into Th1 or Th17 inflammatory cells. Regulatory T cells can also release high amounts of dopamine that acts in an autocrine DAR-mediated manner to inhibit their suppressive activity. These dopaminergic regulations could represent a driving force during autoimmunity. Indeed, dopamine levels are altered in the brain of mouse models of multiple sclerosis (MS) and lupus, and in inflamed tissues of patients with inflammatory bowel diseases or rheumatoid arthritis (RA). The distorted expression of DARs in peripheral lymphocytes of lupus and MS patients also supports the importance of dopaminergic regulations in autoimmunity. Moreover, dopamine analogs had beneficial therapeutic effects in animal models, and in patients with lupus or RA. We propose models that may underlie key roles of dopamine and its receptors in autoimmune diseases.
24708419 Protection against collagen-induced arthritis in mice afforded by the parasitic worm produ 2014 Mar We have previously reported that ES-62, a molecule secreted by the parasitic filarial nematode Acanthocheilonema viteae, protects mice from developing collagen-induced arthritis (CIA). Together with increasing evidence that worm infection may protect against autoimmune conditions, this raises the possibility that ES-62 may have therapeutic potential in rheumatoid arthritis and hence, it is important to fully understand its mechanism of action. To this end, we have established to date that ES-62 protection in CIA is associated with suppressed T helper type 1 (Th1)/Th17 responses, reduced collagen-specific IgG2a antibodies and increased interleukin-10 (IL-10) production by splenocytes. IL-10-producing regulatory B cells have been proposed to suppress pathogenic Th1/Th17 responses in CIA: interestingly therefore, although the levels of IL-10-producing B cells were decreased in the spleens of mice with CIA, ES-62 was found to restore these to the levels found in naive mice. In addition, exposure to ES-62 decreased effector B-cell, particularly plasma cell, infiltration of the joints, and such infiltrating B cells showed dramatically reduced levels of Toll-like receptor 4 and the activation markers, CD80 and CD86. Collectively, this induction of hyporesponsiveness of effector B-cell responses, in the context of the resetting of the levels of IL-10-producing B cells, is suggestive of a modulation of the balance between effector and regulatory B-cell responses that may contribute to ES-62-mediated suppression of CIA-associated inflammation and inhibition of production of pathogenic collagen-specific IgG2a antibodies.
27747493 Refining the Management of Rheumatoid Arthritis: the Benefits of Subcutaneous Tocilizumab. 2015 Jun Rheumatoid arthritis (RA) is a chronic systemic autoimmune condition which affects approximately 1% of the adult population worldwide and is characterized by joint inflammation, with extra-articular features being common. Interleukin 6 (IL-6) is one of the chief pro-inflammatory cytokines found in the joints and sera of patients with RA. Increased levels of IL-6 correlate with inflammation, disease activity, and radiological damage. RA treatment should focus on minimizing the signs and symptoms of disease (pain, stiffness, and swelling of the joints) and on preventing or minimizing joint damage to preserve functionality and quality of life. The benefits of early, intensive intervention are now acknowledged, with all patients with newly diagnosed, active RA being started on methotrexate (MTX) monotherapy or combination therapy. Lack of efficacy, intolerance, and/or toxicity can lead to discontinuation of this drug, and there is a need for exploring further treatment options. In the UK, patients with persistently high disease activity who have failed at least two conventional disease-modifying agents (DMARDs) including MTX may qualify for biologic therapy. Numerous trials have shown intravenous (IV) tocilizumab (TCZ), a biologic drug targeting and inhibiting IL-6, to be effective for controlling inflammation in RA, with an acceptable safety profile. Its superiority in monotherapy when compared with other biologic agents makes it the drug of choice for patients who are intolerant or have contraindications to traditional DMARDs. However, one of the drawbacks of IV TCZ is the requirement for monthly infusions, which is inherently inconvenient for the patient and associated with increased cost. Subcutaneous (SC) TCZ has now been approved following two clinical trials which showed similar efficacy and safety compared to IV TCZ, and better efficacy compared to placebo (SUMMACTA and BREVACTA trials, respectively). Respiratory infections are the most common side effects in patients receiving SC TCZ. Advantages of SC formulations include convenience and reduced cost compared with IV therapies. Overall, patients tend to have a preference for SC over IV administration of medications. Close monitoring of patients should be undertaken in all cases, paying particular attention to the full blood count, liver enzymes, and cholesterol levels.
25232418 Prevalence of metabolic syndrome in women with rheumatoid arthritis and effective factors. 2014 PURPOSE: Metabolic syndrome (MS), which is framed by cardiovascular risk factors such as hypertension, obesity, glucose intolerance and dyslipidemia, is thought to be associated with the rheumatic diseases. The aim of this study is to examine the frequency of metabolic syndrome (MS) and insulin resistance in patients with rheumatoid arthritis (RA) and to examine the effect of the inflammation symptoms, disease activity and drugs used in treating RA on insulin resistance and presence MS. METHOD: One hundred women patients diagnosed with RA according to the American College of Rheumatology (ACR) diagnosis criteria and 100 healthy women were included in the study as controls. Insulin resistance were evaluated using the homeostasis model assessment for insulin resistance (HOMA-IR) method and MS was diagnosed according to two Metabolic Syndrome definitions (National Cholesterol Education Programme 2004, International Diabetes Federation). The disease activity of RA was evaluated by the disease activity score including 28 joints (DAS28). RESULTS: In total, 27% and 33% of the RA patients and 28% and 44% of the control group patients according to the diagnostic criteria used were also MS patients. There was no significant difference between the RA and control groups in MS frequency and insulin resistance according to two diagnostic criteria used. The DAS28, erythrocyte sedimentation speed (ESS) and serum uric acid levels in the RA patients with MS were significantly higher than those of the RA patients without MS. The prevalence of MS Ä°n patients with RA using methotrexate (MTX) was significantly lower than without RA. Other drugs used in treatment of RA had no effect on the prevalence of MS in patients with RA. CONCLUSION: Controlling inflammation and disease activity can reduce the MS frequency of RA patients and MTX treatment also may be a protective factor against MS.
27708861 Prevalence of the metabolic syndrome in rheumatoid arthritis. 2014 Mar OBJECTIVE: Patients with rheumatoid arthritis (RA) experience a markedly increased prevalence of cardiovascular disease (CVD), but the causal factors have yet to be completely elucidated. Metabolic syndrome (MetS) is a cluster of risk factors of CVD and identifies additional cardiovascular risk beyond the sum of its individual components. In this study, we investigated the prevalence of MetS and its possible relationship with disease-related factors in patients with RA. MATERIAL AND METHODS: Fifty-two patients with RA and 30 age- and sex-matched healthy controls were studied. Adult Treatment Panel III of the National Cholesterol Education Program (NCEP-ATP III) and modified World Health Organization (WHO) criteria were used to define MetS. RA disease activity is assessed by the disease activity score of 28 joints (DAS28), and the functional status of patients was evaluated by Health Assessment Questionnaire (HAQ). RESULTS: Although there was no difference between groups regarding the frequency of MetS according to NCEP-ATP III criteria (17.3% and 6.5% in RA and control groups, respectively (p=0.158)) if modified WHO criteria were used, the prevalence of MetS was significantly higher in patients with RA (28.8%) than in controls (9.7%) (p=0.04). Central obesity and hypertension were found to be more frequent in patients with RA by both NCEP-ATP III and WHO criteria. RA patients with MetS had higher systolic and diastolic blood pressure, BMI and frequency of smoking than patients without MetS. Disease-related factors were similar in RA patients with or without MetS. CONCLUSION: The evaluation of patients with RA for MetS, which is a multidimensional risk factor of CVD, may be beneficial.
24416634 Galectins in the Pathogenesis of Rheumatoid Arthritis. 2013 Sep 30 Rheumatoid arthritis (RA) is a complex and common systemic autoimmune disease characterized by synovial inflammation and hyperplasia. Multiple proteins, cells, and pathways have been identified to contribute to the pathogenesis of RA. Galectins are a group of lectins that bind to β-galactoside carbohydrates on the cell surface and in the extracellular matrix. They are expressed in a wide variety of tissues and organs with the highest expression in the immune system. Galectins are potent immune regulators and modulate a range of pathological processes, such as inflammation, autoimmunity, and cancer. Accumulated evidence shows that several family members of galectins play positive or negative roles in the disease development of RA, through their effects on T and B lymphocytes, myeloid lineage cells, and fibroblast-like synoviocytes. In this review, we will summarize the function of different galectins in immune modulation and their distinct roles in RA pathogenesis.
24358069 The Effect of Socioeconomic Class and Immigrant Status on Disease Activity in Rheumatoid A 2013 BACKGROUND: There have been no reports on the effect of immigrant status and socioeconomic status on outcome in rheumatoid arthritis (RA) in Sweden. METHODS: Between 1992 and 2006, 2,800 patients were included in the BARFOT study on early RA in Sweden. Disease Activity Score 28 joints (DAS28), Health Assessment Questionnaire (HAQ), treatment and European League Against Rheumatism (EULAR) response criteria were registered. In 2010, 1,430 patients completed a questionnaire enquiring about demographics and lifestyle factors. RESULTS: One hundred and thirty-nine of the 1,430 patients (9.7%) were immigrants. At baseline immigrants had higher mean HAQ (1.2 vs 0.97 for non-immigrants, p=0.001), DAS28 (5.6 vs 5.2, p=0.000), visual analog scale (VAS) pain (56 mm vs 45 mm, p=0.000), VAS global health (53 mm vs 44 mm, p=0.000) and tender joint count (TJC) (10 vs 8, p=0.000). These differences persisted for up to 2 years of follow-up (for HAQ, for up to 8 years of follow-up). Immigrant status did not have any effect on swollen joint count (SJC), ESR, CRP or EULAR response. Socioeconomic class did not have any effect on treatment or outcome. CONCLUSIONS: Immigrants scored worse in pain, function and TJC for up to 2 years of follow-up, but they did not differ from non-immigrants in objective measures of inflammation or EULAR outcome. This could be due to different perceptions of health and pain and/or the stress of immigration. Socioeconomic class had no effect on treatment or outcome, and this could be due to the relatively egalitarian society in Sweden.
23899969 Construction and psychometric properties of the Belgian Rheumatoid Arthritis Disability As 2013 Jul OBJECTIVES: To describe the construction and psychometric properties of the Belgian Rheumatoid Arthritis Disability Assessment (BRADA) questionnaire, a self-report tool to evaluate chronic activity limitations in patients with rheumatoid arthritis (RA). The BRADA was developed to assess the eligibility of patients with RA for financial and social support measures. METHODS: The BRADA questionnaire evaluates functioning in 6 functional domains (mobility, nutrition, self care, household tasks, awareness of danger and communication) over the past week and the past 3 months. To assess the psychometric properties of the BRADA, patients with moderate to severe RA filled out the BRADA, HAQ-DI and SF-36 questionnaires twice, with a four-week interval. At each visit, the total number of swollen and tender joints, and global disease activity were recorded. DAS 28 was measured at the first visit. Internal consistency of items per domain was evaluated with Cronbach's alpha method. Intraclass correlation coefficient (ICC) analysis was used to assess test-retest reliability. BRADA scores were compared to HAQ, SF-36 scores and disease activity parameters with Spearman's Rho correlation coefficients to assess construct validity. RESULTS: Experts considered the content and face validity of BRADA to be adequate. Internal consistency was satisfactory for all functional domains (alpha >0.75), as was the test-retest reliability (ICC 0.78). BRADA scores showed excellent correlation with other validated questionnaires in RA (HAQ-DI, SF-36) and with measures of disease activity (VAS, DAS28)(p<0.001). CONCLUSIONS: Its psychometric properties indicate that the BRADA questionnaire is a suitable instrument to evaluate disease-specific activity limitations in patients with RA.
23749610 Non-steroidal anti-inflammatory drugs and risk of cardiovascular disease in patients with 2014 Aug OBJECTIVE: To examine the risk of major cardiovascular disease associated with non-steroidal anti-inflammatory drugs (NSAIDs) in a large 'real-world' contemporary rheumatoid arthritis (RA) cohort. METHODS: A longitudinal cohort study was conducted with use of Danish nationwide individual-level registry data on inpatient and outpatient health care provision, pharmacotherapy and income during 1997-2009. 17 320 RA patients were identified and matched with 69 280 controls (4 : 1) by age and sex. NSAID-associated risk of major cardiovascular disease defined as the combined endpoint of myocardial infarction, stroke or cardiovascular mortality was assessed in multivariable survival models. RESULTS: During follow-up (median 4.9 years) 6283 events occurred. The cardiovascular risk associated with overall NSAID use was significantly lower in RA patients than in controls (HR 1.22 (95% CI 1.09 to 1.37) vs 1.51 (1.36 to 1.66), p<0.01). The pattern of lower NSAID-associated risk in RA patients was generally found with the individual NSAIDs investigated. While use of rofecoxib (HR 1.57 (1.16 to 2.12)) and diclofenac (HR 1.35 (1.11 to 1.64)) was associated with increased cardiovascular risk in RA patients, there was no significant risk increase associated with use of other NSAIDs in these patients. CONCLUSIONS: The cardiovascular risk associated with NSAID use in RA patients was modest and significantly lower than in non-RA individuals. Moreover, only a few of the individual NSAIDs were associated with increased cardiovascular risk. NSAID use should be assessed in the individual patient based on the indication for pain relief and risk factors for adverse effects, and not automatically be avoided due to concerns of severe cardiovascular outcomes alone.
25364755 Intractable diseases treated with intra-bone marrow-bone marrow transplantation. 2014 Bone marrow transplantation (BMT) is used to treat hematological disorders, autoimmune diseases (ADs) and lymphoid cancers. Intra bone marrow-BMT (IBM-BMT) has been proven to be a powerful strategy for allogeneic BMT due to the rapid hematopoietic recovery and the complete restoration of T cell functions. IBM-BMT not only replaces hematopoietic stem cells (HSCs) but also mesenchymal stromal cells (MSCs). MSCs are multi-potent stem cells that can be isolated from bone marrow (BM), umbilical cord blood (UCB), and adipose tissue. MSCs play an important role in the support of hematopoiesis, and modify and influence the innate and adaptive immune systems. MSCs also differentiate into mesodermal, endodermal and ectodermal lineage cells to repair tissues. This review aims to summarize the functions of BM-derived-MSCs, and the treatment of intractable diseases such as rheumatoid arthritis (RA) and malignant tumors with IBM-BMT.
24025117 An atypical case of lymphoproliferative pulmonary involvement in a patient with Sjögren's 2013 Sep 11 BACKGROUND: Sjögren's syndrome is characterized by lymphocytic infiltration of the exocrine glands, together with polyclonal B-cell activation, and lung diseases are well-known complications of the disease. Therefore, in most cases associated with Sjögren's syndrome, infiltrating lymphocytes in the lung specimen exhibit the features of B-cells. We herein report an atypical case of lymphoproliferative pulmonary involvement in a patient with Sjögren's syndrome. CASE PRESENTATION: A 46-year-old female was admitted to our hospital because of an abnormal chest roentgenogram finding on a medical checkup. Chest computed tomography showed randomly-distributed micronodules and patchy ground-glass opacities. A surgical biopsied specimen showed an atypical pattern of interstitial pneumonia with numerous lymphoid follicles. Among the infiltrating lymphocytes in the lung, only the monoclonality of the T-cells was proven by a gene rearrangement analysis, but there was no cytological atypicality or genetic disorder revealed by testing the bone marrow aspirate. A diagnosis of Sjögren's syndrome was made based on the patient's other symptoms and these negative findings. The patient's pulmonary lesions have been successfully treated and remission has been maintained for over three years with corticosteroid treatment alone. CONCLUSION: The present patient was an atypical case of lymphoproliferative pulmonary involvement in a patient with Sjögren's syndrome. Although monoclonality of the infiltrating T-cells was proven, the clinical course and the findings of the imaging and laboratory examinations were inconsistent with the previously-reported cases of primary pulmonary T-cell lymphoma. This suggests that the monoclonality of lymphocytes does not always define malignancy. The diagnosis of malignant lymphoma or lymphoproliferative diseases should be made clinically, pathologically and cytogenetically to rule out other similar diseases.
23340181 Emerging avenues linking inflammation, angiogenesis and Sjögren's syndrome. 2013 Mar Sjögren's syndrome (SS) is an autoimmune disease characterized by an inflammatory mononuclear infiltration and the destruction of epithelial cells of the lachrymal and salivary glands. The aetiology is unknown. The expression "autoimmune epithelitis" has been proposed as an alternative to SS, in view of the emerging central role of the epithelial cells in the disease pathogenesis. At the biomolecular level, the epithelial cells play an important role in triggering the autoimmune condition via antigen presentation, apoptosis, and chemokine and cytokines release. Inflammation and angiogenesis are frequently coupled in the pathological conditions associated to autoimmune diseases, and an angiogenic imbalance contributes to the pathogenesis of a number of inflammatory disorders. This work reviews the current knowledge of the molecular and cellular mechanisms underlying the pathogenesis of the inflammatory reactions that characterize SS. The literature and our data on the role of angiogenesis in the pathophysiology of the disease are discussed.
27747761 Current Practice Patterns and Educational Needs of Rheumatologists Who Manage Patients wit 2014 Dec INTRODUCTION: As the therapeutic landscape for rheumatoid arthritis (RA) continues to change, it is relevant to examine current treatment patterns among rheumatologists. The purpose of this study was to identify attitudes and practices of US rheumatologists with respect to RA. METHODS: Nine-hundred and one US-practicing rheumatologists were sent electronic invites (via email or fax) to participate in a case-vignette survey in April 2013. All respondents were currently practicing rheumatology and seeing at least one RA patient per week. The survey examined current attitudes, existing knowledge, management choices and perceived barriers in the management of RA. Data collection stopped once 125 responses were received. RESULTS: Approximately half of the 125 respondents were very familiar with current clinical practice guidelines for RA diagnosis and management. There was no consensus on which validated tools to use when assessing RA severity, with 54% using Physician Global Assessment and 34% using Disease Activity Score 28 at initial assessment. Most respondents (74%) used methotrexate (MTX) as initial therapy for a newly diagnosed RA patient. Eighty-six percent of respondents would add a tumor necrosis factor inhibitor (TNFi) when MTX alone could not control RA. There was no consensus on which treatment should be used when a TNFi is ineffective. The majority of respondents (66% of respondents) would prescribe TNFis indefinitely in patients with continued response. If a patient was in stable remission on MTX and a TNFi, respondents were most likely to maintain this regimen (53% of respondents); a notable minority (43%) would lower the MTX dose. When prescribing biologics, respondents were most concerned with infection; infection was considered a very significant barrier to biologic use. Although 98% of respondents indicated that they personally educate patients about RA, only 42% provide written material. CONCLUSIONS: The lack of consistency in responses suggests that rheumatologists may benefit from continuing medical education on; clinical practice guidelines; the most recent evidence for management of patients in remission; the use of biologic agents after infection; and management of patients with RA and comorbidities.
24587950 The Interaction Between Allelic Variants of CD86 and CD40LG: A Common Risk Factor of Aller 2014 Mar PURPOSE: Allergic asthma (AA) and rheumatoid arthritis (RA) are immune tolerance-related diseases, and immune tolerance is known to be influenced by costimulatory molecules. In this study, we sought to identify common genetic susceptibility in AA and RA. METHODS: Two hundred cases of AA, 184 cases of RA, and 182 healthy controls were recruited at the Seoul National University Hospital, Seoul, Korea. Eight single nucleotide polymorphisms (SNPs) in five genes coding costimulatory molecules, namely, -318C>T, +49A>G, and 6230G>A in CTLA4, IVS3+17T>C in CD28, -3479T>G and I179V in CD86, -1C>T in CD40, and -3458A>G in CD40LG were scored, and genetic interactions were evaluated by multifactor dimensionality reduction (MDR) analysis. RESULTS: MDR analysis revealed a significant gene-gene interaction between -3479T>G CD86 and -3458A>G CD40LG for AA. Subjects with the T/T genotype of -3479T>G CD86 and the A/A genotype of -3458A>G CD40LG were found to be significantly more likely to develop AA than those with the T/T genotype of -3479T>G CD86 and A/- genotype of -3458A>G CD40LG (adjusted OR, 6.09; 95% CI, 2.89-12.98; logistic regression analysis controlled by age). Similarly those subjects showed a significant risk of developing RA (adjusted OR, 39.35; 95% CI, 15.01-107.00, logistic regression analysis controlled by age). CONCLUSIONS: Our findings suggest that a genetic interaction between CD86 and CD40LG favors the development of both AA and RA.
24027365 Anti-CCP antibody in patients with established rheumatoid arthritis: Does it predict adver 2013 Jun BACKGROUND: Rheumatoid arthritis (RA) is an independent risk factor for adverse cardiovascular (CV) events that accounts for a significant proportion of mortality among these patients. Anti-CCP antibodies are associated with higher frequency of extra-articular manifestations and poorer outcomes in RA. AIMS: To determine the role of anti-cyclic citrullinated peptide (CCP) antibody as an independent risk factor for developing CV complications as documented by carotid intima medial thickness and abnormal echocardiography in established RA patients. MATERIALS AND METHODS: Eighty patients of RA having disease duration of at least 3 years participated in this hospital-based, cross-sectional, and observational study. Forty patients were anti-CCP antibody positive. Patients of established RA having known CV risk factors, known heart disease, or family history of premature ischemic heart disease were excluded. RESULTS: Anti-CCP positive group had early morning stiffness, tender and swollen joint count, and c-reactive protein (CRP) level significantly higher than those in anti-CCP negative group. Average intima-medial thicknesses of common carotid arteries were also significantly higher among anti-CCP positive group (P = 0.029) and were positively correlated with patients' age and disease duration. Lower left ventricular ejection fraction and left ventricular diastolic dysfunction were more commonly dispersed among the anti-CCP positive patients with P values of 0.01 and 0.034, respectively. Mild pericardial thickening was documented among 12.5% patients of anti-CCP positive group, while none of the anti-CCP negative patients had similar findings in echocardiography. CONCLUSION: This study stressed on the important role of anti-CCP antibody in myocardial dysfunction due to inflammation in RA patients. Both atherosclerotic vascular involvement and cardiac abnormalities including pericardial, myocardial, and endocardial involvements were higher among anti-CCP positive RA patients. Hence, patients with high titer of anti-CCP antibody associated with prolonged disease duration and increased disease activity should be evaluated for CV morbidity more meticulously.
25197291 The association of body mass index with disease activity and clinical response to combinat 2014 Jun BACKGROUND: The role of obesity in clinical curse of rheumatoid arthritis (RA) is not clear. We investigated the association of obesity and adiposity with disease activity and clinical response to combination therapy in RA patients. MATERIALS AND METHODS: Active RA patients with the disease activity score using 28 joint counts (DAS28) > 2.6 were studied. Height, weight, and waist and hip circumferences were measured and body mass index (BMI) and waist to hip ratio were calculated. Patients were treated with methotrexate (7.5 to 10 mg/week) plus hydroxychloroquine (200 to 400 mg/day) and prednisolone (2.5 to 10 mg/day) and were followed by DAS28 for up to 24 weeks. RESULTS: One hundred and six patients were studied; age = 48.5 ± 13.8 years, 87.7% female, disease duration = 4.4 years [SE = 0.48]. DAS28 was decreased from 4.5 ± 1.6 to 2.9 ± 1.4 (P < 0.001) after 24 weeks of treatment. Only in patients with disease duration of ≤2 years, BMI (r = -0.415, P = 0.005) and waist circumference (r = -0.296, P = 0.05) were correlated with baseline DAS28. Although BMI (r = -0.337, P = 0.025) and waist circumference (r = -0.315, P = 0.038) were correlated with change in DAS28 after therapy, these correlations were disappeared after controlling for baseline DAS28. CONCLUSION: Obesity and adiposity are associated with less severe disease activity in early stage of RA, but are not associated with response to combination therapy with methotrexate plus hydroxychloroquine in RA patients.
27708886 The correlation between ferritin level and acute phase parameters in rheumatoid arthritis 2014 Sep OBJECTIVE: In this study, we evaluated the relationship between ferritin levels and disease activation in rheumatoid arthritis (RA) patients. MATERIAL AND METHODS: We included 44 patients with RA, 20 patients with systemic lupus erythematosus (SLE), 25 patients with infection, 22 patients with malignancy, and 20 healthy control subjects. Erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), whole blood count, and serum iron parameters were determined in all cases. The joint findings in RA patients were recorded, and disease activity score (DAS) was calculated. In SLE patients, antinuclear antibody (ANA) and anti-dsDNA titers and C3 and C4 complement levels were determined. SLE disease activity index (SLEDAI) score was calculated. RESULTS: Serum ferritin levels in the RA, SLE, and control groups were lower than those in the infection and malignancy groups (p<0.05). The ferritin levels in the RA group did not differ significantly from the SLE and control groups. In RA patients, serum ferritin level had a positive correlation with ESR, CRP, RF, platelet count, and DAS score and had a negative correlation with hematocrit (all p values <0.05). In SLE patients, on the other hand, serum ferritin had a positive correlation with ANA, anti-dsDNA, and SLEDAI (all p values <0.05). According to DAS, ferritin level in inactive RA patients was lower than that in active RA patients. When transferrin saturation was considered, iron deficiency anemia was a quite frequent finding in both active and inactive RA patients. CONCLUSION: Interestingly, we observed that ferritin level in RA patients was similar to the control group; however, it was a good parameter of disease activation. This is because a reduction in storage iron and resultant iron deficiency anemia are very common in RA patients.
25050094 The use of biologic DMARDs identifies rheumatoid arthritis patients with more optimistic e 2014 Jul BACKGROUND: Preoperative expectations of total knee arthroplasty (TKA) correlate with postsurgical satisfaction, and are linked to outcomes. Rheumatoid arthritis (RA), and other chronic diseases, may lower expectations, although new biologic medications have greatly enhanced patients' quality of life. QUESTIONS/PURPOSES: The purpose of this study is to compare preoperative expectations of RA to those of matched osteoarthritis (OA) patients undergoing TKA, and examine the subset of RA on biologic DMARD therapy. METHODS: For a cross-sectional study, RA and OA identified from an institutional TKA registry were matched on age, sex, prior TKA, and preoperative function. Expectations were measured using the Hospital for Special Surgery (HSS) Knee Expectations Survey. Expectations and quality of life measures were assessed preoperatively and scores were compared between RA and OA. RESULTS: One hundred fourteen RA cases, 46.5% on biologics, were matched to 228 OA cases. The average expectations score was not significantly lower for RA compared to OA (72.9 ± 20.7 vs. 77.2 ± 18.3, p = 0.040. RA on biologics had expectations similar to OA (total expectation score 76.3 ± 18.1 vs. 77.4 ± 17.4, p = 0.71), while RA not on biologics had expectations that were significantly lower (69.9 ± 22.4 vs. 77.1 ± 19.0, p = 0.03). CONCLUSION: Use of biologics in RA patients was associated with higher expectations, similar to those of OA patients, but the effect on outcomes is not known. Further studies should assess the effect of higher expectations in RA patients on outcomes.