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ID PMID Title PublicationDate abstract
21339227 miR-124a as a key regulator of proliferation and MCP-1 secretion in synoviocytes from pati 2011 Mar MicroRNAs (miRNA) are a class of small endogenous non-coding RNAs that influence the stability and translation of messenger RNA. Synoviocytes from patients with rheumatoid arthritis (RA) were analysed for their miRNA expression profile, and it was found that miR-124a levels significantly decreased in RA synoviocytes as compared with osteoarthritis synoviocytes. Transfection of miR-124a into RA synoviocytes significantly suppressed their proliferation and arrested the cell cycle at the G1 phase. miR-124a directly binds to the 3'-untranslated region of cyclin-dependent kinase 2 (CDK-2) and monocyte chemoattractant protein 1 (MCP-1) mRNA, and the induction of miR-124a in RA synoviocytes significantly suppressed the production of the CDK-2 and MCP-1 proteins. It is proposed that miR-124a is a key miRNA in the post-transcriptional regulatory mechanisms of RA synoviocytes, and has a therapeutic potential.
21899643 Interpreting clinical trial results for moderate-to-severe rheumatoid arthritis: practical 2011 Sep PURPOSE: To provide a general overview of clinical trials and more specifically define measurements common to rheumatoid arthritis clinical trials for the purpose of providing a foundation for rheumatology healthcare providers to translate clinical trial findings into their clinical practice and enhance their patient education discussions. DATA SOURCES: English-language publications cited in the MEDLINE database were used to develop the content of this review article. CONCLUSIONS: The role of rheumatology healthcare providers has evolved to include numerous vital functions, such as expanding communication between specialists and primary care providers, patient education and counseling, assistance with coping strategies, monitoring response to therapy, and administration of therapy. Education regarding clinical trial design, rationale, and discussion of endpoints has not been strongly emphasized for rheumatology healthcare providers who are increasingly introduced to novel agents and need to assimilate findings from clinical trials into daily practice. IMPLICATIONS FOR PRACTICE: Familiarity with the basics of clinical trial design and efficacy endpoints of new rheumatoid arthritis therapeutics, translation and application of that knowledge into daily practice, and the ability to explain this information with patients will further enhance the ability of the rheumatology healthcare provider to optimize care for their patients with rheumatoid arthritis.
22930111 [Systematic literature research for S1 guidelines on sequential medical treatment of rheum 2012 Sep BACKGROUND: On behalf of the German association of Rheumatology national experts developed guidelines for the medical treatment of rheumatoid arthritis (RA) based on the EULAR recommendations for the management of RA published in 2010. Current evidence was provided with an update of the systematic literature review (SLR). The methods and results of the SLR are presented in this article. MATERIALS AND METHODS: An update of the EULAR SLR for the medical treatment of RA was performed from January 2009 to August 2011. The SLR assessed all controlled studies dealing with the outcome in clinical aspects, function and structure of disease modifying treatment of RA. RESULTS: Out of 6,869 screened publications, 138 articles and 56 abstracts were considered in the development of the German guidelines on the treatment of RA. A modified set of recommendations was approved in a consensus of national experts. CONCLUSION: A systematic literature research provided current evidence for the German recommendations on the sequential medical treatment of RA.
21278075 The relevance of citrullinated vimentin in the production of antibodies against citrullina 2011 May Antibodies against citrullinated proteins (ACPAs) are highly specific for RA. Since the discovery of these antibodies, several of studies that focused on the presence and identity of citrullinated proteins in the joints of RA patients have been carried out. The best-known antigens that bind ACPAs are citrullinated filaggrin, Type II collagen (CII), α-enolase, fibrinogen and vimentin. This review compares citrullinated filaggrin, CII, α-enolase and fibrinogen with vimentin in their contribution to ACPA triggering, and gives an overview of the literature in which the role of citrullinated and non-citrullinated vimentin in the onset of ACPA production and the pathogenesis of RA is discussed.
23218433 Impact of socioeconomic gradients within and between countries on health of patients with 2012 Oct In this chapter, we discuss challenges in collecting data on outcomes of patients who receive usual rheumatology care. We present results of the multinational Quantitative Monitoring of Patients with Rheumatoid Arthritis (QUEST RA) study which is a successful example of quantitative clinical measuring of RA as part of routine clinical care in a large number of centres across more than 30 countries. We further elaborate on what we can learn from these data about inequalities and inequities, both within and between countries. Frameworks to understand socioeconomic determinants of health are presented and, in addition to the QUEST RA data, the literature is summarised to provide further evidence on how socioeconomic determinants can contribute to health disparities of patients within and between countries.
21539724 Biochemical markers of ongoing joint damage in rheumatoid arthritis--current and future ap 2011 Apr 28 Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease associated with potentially debilitating joint inflammation, as well as altered skeletal bone metabolism and co-morbid conditions. Early diagnosis and aggressive treatment to control disease activity offers the highest likelihood of preserving function and preventing disability. Joint inflammation is characterized by synovitis, osteitis, and/or peri-articular osteopenia, often accompanied by development of subchondral bone erosions, as well as progressive joint space narrowing. Biochemical markers of joint cartilage and bone degradation may enable timely detection and assessment of ongoing joint damage, and their use in facilitating treatment strategies is under investigation. Early detection of joint damage may be assisted by the characterization of biochemical markers that identify patients whose joint damage is progressing rapidly and who are thus most in need of aggressive treatment, and that, alone or in combination, identify those individuals who are likely to respond best to a potential treatment, both in terms of limiting joint damage and relieving symptoms. The aims of this review are to describe currently available biochemical markers of joint metabolism in relation to the pathobiology of joint damage and systemic bone loss in RA; to assess the limitations of, and need for additional, novel biochemical markers in RA and other rheumatic diseases, and the strategies used for assay development; and to examine the feasibility of advancement of personalized health care using biochemical markers to select therapeutic agents to which a patient is most likely to respond.
21455249 Rheumatoid arthritis: Are ACPA-positive and ACPA-negative RA the same disease? 2011 Apr Seemingly contrasting genetic backgrounds in anti-citrullinated-protein antibody (ACPA)-positive and ACPA-negative rheumatoid arthritis (RA) support the notion that these are in fact two distinct disease subsets, with different underlying pathogenesis, that might need tailored treatment strategies.
21068083 Cardiovascular morbidity and mortality in patients with rheumatoid arthritis: vascular alt 2011 Jan Mortality in patients with rheumatoid arthritis (RA) is higher than in the general population, which is due mainly to premature cardiovascular disease. Traditional cardiovascular risk factors cannot entirely explain the higher level of cardiovascular complications, and there is growing evidence that chronic inflammation is the main culprit. The aims of this review of the literature are to (i) summarize aspects of vascular alterations found in the cardiovascular system of RA patients and to relate them to the clinically relevant cardiovascular morbidity and mortality and (ii) evaluate what these abnormalities and complications might in the end imply for clinical management. A number of abnormalities in the cardiovascular system of RA patients have been identified, on the molecular level, in endothelial function, arterial stiffness, arterial morphology and, finally, in the clinical presentation of cardiovascular disease. Cardiovascular risk assessment should be part of the care of RA patients. While a great deal of data is published demonstrating abnormalities in the cardiovascular system of these patients, it is much less clear what specific interventions should be performed to reduce the incidence of cardiovascular complications. Cardiovascular care should be delivered in accordance with recommendations for the general population. Whether specific drugs (e.g. statins, aspirin) are of particular benefit in RA patients needs further investigation. Control of inflammation appears to be of benefit. Methotrexate and tumor necrosis factor-α blocking agents might reduce the number of cardiovascular events. Leflunomide, cyclosporine, non-steroidal anti-inflammatory drugs and cyclo-oxygenase-2 inhibitors may worsen cardiovascular outcome. The role of glucocorticoids in active RA remains to be determined.
21497675 Inflammatory memories: is epigenetics the missing link to persistent stromal cell activati 2011 Jul Rheumatoid arthritis (RA) is a chronic inflammatory disease leading to joint destruction. Synovial fibroblasts are recognized as key cells in the pathogenesis of RA since they attract and activate immune cells and produce matrix degrading enzymes. Most notably synovial fibroblasts from patients with RA are stably activated and produce high levels of disease-promoting molecules without further stimulation by immune cells. Accumulating data suggest that epigenetic changes in stromal cell populations might be crucially involved in the pathology of RA and other chronic inflammatory diseases. In the current review, we discuss the mechanisms by which epigenetic changes might cause the stable activation of synovial fibroblasts in RA and how changes in the epigenome might alter immune function and inflammatory response and thereby promote the development of chronic diseases.
21176803 The rheumatoid metacarpophalangeal joint. 2011 Feb Rheumatoid metacarpophalangeal joint deformities remain an important cause of disability. Surgical intervention in carefully selected patients improves function and prolongs independence. This article discusses the commonly used reconstructive techniques and their benefits. Case selection through a combined clinic with rheumatologists and hand therapists is recommended.
21136261 The swollen joint, the thickened artery, and the smoking gun: tobacco exposure, citrullina 2011 May Autoimmune diseases result from an interplay between susceptibility genes and environmental factors. These interacting etiopathogenetic components converge in a critical step preceding disease, the loss of tolerance to self. In this review, we examine the evidences linking tobacco smoking with the initiation and perpetuation of inflammation affecting both the synovial membrane and the endothelial lining in patients with rheumatoid arthritis. This disease is a compelling argument for the decisive role of environment in the triggering of a human autoimmune disease in genetically prone individuals.
21357993 Impact of salivary flow and lysozyme content and output on the oral health of rheumatoid a 2011 Feb 1 PURPOSE: The aim of the study was to examine salivary flow rate, DMF index, lysozyme concentration and its output in two groups of rheumatoid patients and to compare the results with those of healthy controls. MATERIAL/METHODS: Rheumatoid arthritis (RA) patients were divided into two study groups: with reduced salivary flow rate ≤0.15 ml/min (RA HS, hyposalivation) and with normal salivary secretion rate >0.2 ml/min (RA NS, normal salivation). The healthy control group (C) was recruited from the Department of Conservative Dentistry. Salivary lysozyme concentration was determined by radial immunodiffusion. ANOVA followed by LSD test were used for the statistical analysis. RESULTS: We found that lysozyme concentration was higher and lysozyme output and salivary flow rate were statistically lower in the RA HS group in comparison to the RA NS and C groups. The DMF index was statistically higher in both RA groups in comparison to the control group. CONCLUSIONS: RA disease impacts negatively on oral health and salivary parameters. Hyposalivation of RA patients increases the negative influence of RA on oral health. RA patients should receive more stomatological attention.
22298069 [Recent progress in the treatment of rheumatoid arthritis]. 2012 Feb Rheumatoid arthritis (RA) is a representative autoimmune disease characterized by chronic and destructive inflammatory synovitis that causes severe disability and mortality. Since joint destruction occurs from the early disease, its diagnosis and treatment have to be done timely. 2010 RA classification criteria redefine the current paradigm of RA by focusing on features at earlier stages of disease that are associated with persistent and/or erosive disease. Thus, a new concept of 'treat-to-target' is emerging in treatments of RA, whereby patients are treated according to prespecified goals, such as remission. Accordingly, the combinational use of methotrexate and biologics targeting TNF and IL-6 has revolutionized the treatment of RA, producing significant improvements in clinical and structural outcomes, and has produced upcoming endpoint for the treatment as the clinical and structural remission.
22530636 Cannabinoids: novel therapies for arthritis? 2012 Apr A key feature of osteoarthritis and rheumatoid arthritis is the loss of articular cartilage. Cartilage breakdown is mediated by complex interactions of proinflammatory cytokines, such as IL-1, inflammatory mediators, including nitric oxide and prostaglandin E(2), and proteases, including matrix metalloproteinases and aggrecanases, such as ADAMTS-4 and -5. Cannabinoids have been shown to reduce joint damage in animal models of arthritis. They have also been shown to prevent IL-1-induced matrix breakdown of collagen and proteoglycan, indicating that cannabinoids may mediate chondroprotective effects. Cannabinoids produce their effects via several cannabinoid receptors and it is important to identify the key cannabinoids and their receptors that are involved in chondroprotection. This review aims to outline the current and future prospects of cannabinoids as anti-arthritic therapeutics, in terms of their ability to prevent cartilage breakdown.
21616040 The potential role of Th17 in mediating the transition from acute to chronic autoimmune in 2011 May T helper 17 cells (Th17) have arisen in the last 15 years as major effector cells in several chronic inflammatory states. In synovitis associated with rheumatoid arthritis (RA), Th17 emerged as being involved in driving the active acute phases and correlated with local and systemic parameters of inflammation; in particular, TCRζ(dim) Th17 appear to be the greatest producers of IL-17 at the single-cell level. IL-1beta and IL-6, along with IL-23, arose as the major drivers of differentiation and local development of Th17, while IL-15 and cell-cell contact can trigger the local production of IL-17. TNF-alpha inhibition can reversibly block the migration of pathogenic effector memory TCRzeta(dim) T cells and CCR6+ Th17 from peripheral blood to inflamed tissues. IL-17 is a potent chemoattractant for pre-committed CD4+ T cells and neutrophils, and may promote the migration of B cells to lymphoid follicles in the chronic phase of synovial inflammation. Importantly, IL-17 drives osteoclastogenesis and neoangiogenesis in the RA joint. These data strongly suggest that Th17 are key effector cells in driving the transition from the acute to the chronic phase of RA inflammation.
22991486 Atherogenic index and high-density lipoprotein cholesterol as cardiovascular risk determin 2012 Cardiovascular (CV) diseases are a serious concern in rheumatoid arthritis (RA), accounting for approximately one-third to one-half of all RA-related deaths. Besides the attempts to identify new risk factors, the proper management of traditional CV risk factors such as dyslipidemia should become a priority in the periodic evaluation of every RA patient. Atherogenic index has been suggested to be less susceptible to disease activity variation during large periods of time, making him more attractive to be used in CV risk prediction in this group of patients as compared to individual lipids concentrations. Nevertheless, inflammation may negatively impact HDL antiatherogenic properties, suggesting that HDL function assessment is of particular importance when predicting CV risk in these patients. A tight control of inflammation becomes therefore crucial for a successful CV risk management. The present paper debates these hypotheses focusing on the effects of therapy with biologicals on the above mentioned parameters.
21359506 Introduction to economic modeling for clinical rheumatologists: application to biologic ag 2011 Mar Rheumatoid arthritis (RA) is a chronic, debilitating inflammatory, progressive musculoskeletal disease that affects 0.5-1.0% of the adult population in Western countries. The joint destruction and progressive functional disability associated with uncontrolled RA result in tremendous impacts on health-related quality of life, ability to work, and mortality. In addition, the treatment of the disease and associated complications exact a substantial economic burden to the patients, their families, and society. In the last decade, several biological agents (biologics) have been approved for use in RA, revolutionizing treatment. These biologics, which target cytokines such as tumor necrosis factor or lymphocytes such as B or T cells, reduce functional disability and substantially slow the progression of joint damage. However, because these agents typically cost ten to 100 times more than existing available older drug therapies, there has been worldwide concern regarding their impact on healthcare budgets. As such, there has been increased attention towards economic evaluation as a means to determine whether, and in which subgroup of patients, these newer, more expensive agents confer appropriate value for their additional cost. Indeed, evaluations have guided coverage decisions for both private and public health insurance agencies such as the National Institute for Health and Clinical Excellence in the UK. The use of economic evaluations to determine value for money for these agents has attracted both debate and controversy. Some of the controversy is related to the appropriateness of the structure of, and assumptions underlying, the decision models employed to estimate the long-term costs and benefits of these agents over existing therapies. To fully appreciate the debate, one must first understand the basic principles of economic evaluation and the necessity for using decision models to evaluate cost effectiveness. To understand the basic principles of economic evaluation, we refer the reader to an introductory article aimed at clinical rheumatologists. This paper attempts to explain the rationale for the use of economic modeling approaches to assess the value of biologics for RA using specific examples from the literature.
21885508 OMERACT 10 Sharp Symposium: important findings in examination of imaging methods for measu 2011 Sep The Sharp Symposium was held at the Outcome Measures in Rheumatology Clinical Trials 2010 meeting (OMERACT 10) in honor of the late John Sharp, consummate rheumatologist and researcher. The symposium focused on the status of current scoring methods in radiography, magnetic resonance imaging (MRI), and ultrasound (US) in rheumatoid arthritis (RA), as well as on the use of soluble and tissue biomarkers in RA, with the aim of updating recommendations regarding methods for enhanced detection, monitoring, and prediction of joint damage in clinical trials.
21979315 [Strategies for improved healthcare of people with the endemic disease rheumatism exemplif 2011 Oct New therapeutic principles and considerable diagnostic advances have made it possible to define different rheumatic diseases and especially rheumatoid arthritis (RA) at an early stage and by starting an early and aggressive medication a considerable proportion of patients with RA will reach the status of low disease activity or even remission. With the additional development of composite measures to estimate the disease activity of RA, it was the goal of an international working group consisting of rheumatologists and patients to develop recommendations for treating rheumatoid arthritis in a similar way as for patients with hypertension or diabetes, with the aim to achieve remission as often as possible. This treat-to-target initiative has taken off in quite a number of different countries including Germany leading to discussions on how this initiative can be integrated into the specific national healthcare systems and what possibilities would exist for its implementation. To develop strategies for an improved healthcare of people suffering from rheumatic diseases and using RA as an example, action elements and postulates were developed which will be discussed in more detail in the present manuscript.
21176806 Outcomes research in rheumatoid arthritis. 2011 Feb Although rheumatoid arthritis causes significant disability for more than 1 million individuals in the United States, prior research regarding surgical treatment options has been limited by study sample size, study design, and methods of comparison. Furthermore, there is wide variation in the referral pattern for hand surgery consideration and type of surgical treatment of rheumatoid hand disease, yet the reasons for these differences are unclear. This review describes the role of outcomes research in rheumatoid hand disease by summarizing variations in surgical treatment, detailing current outcome assessment strategies, and offering potential strategies for designing future studies for rheumatoid hand disease.