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ID PMID Title PublicationDate abstract
19995742 Does gene expression analysis inform us in rheumatoid arthritis? 2010 Jan Transcription profiling has become a standard technology in research. It is mainly applied in the search for biomarkers to improve diagnostic and prognostic classification, to quantify disease activity and to predict or indicate response to therapy. This review will focus on rheumatoid arthritis and discuss considerations for sample selection, prerequisites for functional interpretation of data and the current status of information deduced in the field of biomarkers for the various clinical questions. In the next few years, prediction of response to treatment is the most important aim of biomarker research. With the growing number of new biological agents, there is increasing pressure to identify molecular parameters that will not only guide the therapeutic decision but also help to define the most important targets for which new biological agents should be tested in clinical studies.
19524171 Vascular disease in rheumatoid arthritis: from subclinical lesions to cardiovascular risk. 2009 Jul Rheumatoid arthritis (RA) is one of the most prevalent and complex inflammatory diseases affecting primarily the joints, but also associating several extra-articular features. The vascular disease in RA encompasses a large spectrum of lesions, from rheumatoid vasculitis to atherosclerotic lesions. During the last years the importance of the vascular disease related to atherosclerosis in terms of cardiovascular morbidity and global mortality became evident in RA. The inflammatory hypothesis of atherosclerosis in RA implies that mediators originating from the inflamed synovial tissue or from the liver may have systemic vascular consequences, leading to endothelial dysfunction and structural abnormalities of the vessels. Hence, the global management of patients with RA must include the improvement of cardiovascular risk in parallel with the management of joint disease.
19758115 Dyslipidaemia in rheumatoid arthritis: the role of inflammation, drugs, lifestyle and gene 2010 May Rheumatoid arthritis (RA) associates with excess cardiovascular morbidity and mortality, resulting in significantly shortened lifespan. Traditional risk factors (e.g. dyslipidaemia and hypertension) and novel risk factors (e.g. systemic inflammation) contribute to the development of cardiovascular disease (CVD) in RA. In the general population, dyslipidaemia has been found to be central to the development of CVD, playing an important role in all stages of atherosclerotic plaque formation. In RA, lipid metabolism may be altered by systemic inflammation, environmental lifestyle factors, drug therapy and several genetic factors. This may result in changes in overall lipid levels, as well as modifications of lipid/lipoprotein structure and function. In this review, we discuss lipid abnormalities specifically in the context of RA and highlight the potential impact of inflammation, genetic factors, lifestyle, and anti-rheumatic drugs on lipid metabolism.
19339918 The role of MRI in rheumatoid arthritis: research and clinical issues. 2009 Mar PURPOSE OF REVIEW: This review describes the important role of MRI in rheumatoid arthritis (RA), exploring recent reliability and validity work, as well as the current use of MRI in clinical trials and practice. RECENT FINDINGS: Both bone oedema and erosions on MRI have been confirmed as representing osteitis and cortical bone defects, respectively, adding to what was already known about the validity of contrast enhanced synovium representing synovitis. An increasing number of studies have used MRI as an outcome measure with interest moving from disease-modifying antirheumatic drugs (DMARDs) to biological therapies and a more technical focus on dynamic imaging. In addition, low-field extremity MRI has been developed as a well tolerated, comfortable and convenient method for imaging assessment in clinical practice. SUMMARY: This review has highlighted both recent research advances as well as the future potential for MRI in RA, with the aim that MRI will become part of standard measures for RA clinical trials. With respect to extremity imaging, further work is required to provide useful clinical algorithms.
19888501 [TNFalpha blockers and infectious risk in rheumatoid arthritis]. 2009 Jul Patients suffering from rheumatoid arthritis have increased risk of infections when compared with general population. The risk depends directly from disease activity and severity. Furthermore, risk increases with aging, immunosuppressive agents and comorbidities such as diabetes, pulmonary and cardiac diseases. In particular corticosteroids, even at low doses, are a major risk factor. Due to disease related risk it is difficult to separate the risk deriving from the use of TNF alpha blockers. Data from clinical trials, meta-analysis and national registers are somewhat contradictory. In patients with rheumatoid arthritis on routine follow-up, treatment with TNF alpha blockers seems to carry an increased risk of infections compared to traditional DMARDs but not associated with increased risk of overall serious infection. Physicians should carefully monitor for signs of infection when using TNF alpha blockers, particularly shortly after treatment initiation.
19505214 Management of early aggressive rheumatoid arthritis during pregnancy and lactation. 2009 Jun This survey outlines the problems of drug therapy in women with early aggressive rheumatoid arthritis (RA) who desire children, are pregnant, or are lactating. Solutions for treatment that benefit the mother and do not harm the fetus or the breast-fed child are discussed. The most effective immunosuppressive drugs alone or in combination are contraindicated during pregnancy and, to a lesser degree, also during lactation. Judicious timing of therapy is therefore necessary, aiming at fast remission of symptoms with the most effective therapy and maintaining quiescent disease with drugs compatible with pregnancy or lactation.
19889284 Enhanced pain perception in rheumatoid arthritis: novel considerations. 2009 Dec Enhanced pain perception is common among patients with rheumatoid arthritis (RA). Given the putative role of proinflammatory cytokines in the development of hyperalgesia, a greater understanding of factors that facilitate increased cytokine expression in RA stands to increase understanding of the sources of enhanced pain perception. Patients with RA have significantly greater stress-induced proinflammatory cytokine release. Although absolute deficiencies in cortisol have not been demonstrated, functional abnormalities have been described, including "abnormally normal" cortisol levels in the face of increased inflammation and deficient responses to stressful challenges. Parasympathetic insufficiency has also been demonstrated, which may enhance pain perception indirectly through disinhibited cytokine expression. Several psychological variables have also been demonstrated to affect pain perception in patients with RA. Identification of factors that contribute to enhanced pain perception in RA may aid in the development of novel analgesic strategies that, in turn, may decrease disease activity and improve general clinical outcomes.
20828353 Atherosclerotic vascular damage and rheumatoid arthritis: a complex but intriguing link. 2010 Sep Rheumatoid arthritis is a chronic inflammatory disease characterized by a reduced life expectancy mainly due to cardiovascular disease. In long-standing disease, it has been widely demonstrated that both traditional cardiovascular risk and disease-related factors, including chronic inflammation and immune-mediated mechanisms, play a key role in accelerating atherosclerotic damage of the arterial wall. The short- and long-term effects of immunosuppressive treatment on cardiovascular disease outcome is, however, uncertain and a multidisciplinary approach appears to represent the best management of cardiovascular risk in these patients.
20383892 Update on the genetic risk factors for rheumatoid arthritis. 2010 Jan Rheumatoid arthritis (RA) is a complex disease, meaning that multiple genetic variants, environmental factors and random events interact to trigger pathological pathways. Although many of these etiological factors have not yet been identified, recent groundbreaking advances have expanded our knowledge about the genetic factors that contribute to RA. Here, we review the most recent findings on the genetic risk factors for RA. First, we give an overview of the genetics of RA and briefly describe the susceptibility loci discovered prior to the availability of genome-wide association studies (GWAS). Second, we focus on the newly discovered RA loci that have arisen from GWAS in populations of European ancestry. Through these studies, the number of established RA susceptibility loci has now grown to 13. Third, we discuss several important issues emerging from GWAS, such as ethnic heterogeneity and shared autoimmunity risk loci. Finally, we discuss what still needs to be accomplished before a more complete picture of the genetic risk to RA can be attained.
20146863 Visfatin: a potential therapeutic target for rheumatoid arthritis. 2009 Nov Rheumatoid arthritis (RA) is usually a chronic, systemic inflammatory disorder primarily targeting the synovium and articular cartilage. It is incurable, costly and responds poorly to treatment. Methotrexate alone or in combination with conventional and/or biological disease-modifying antirheumatic drugs (DMARDs) is often used to induce remission of active disease. The effectiveness of treatment is, however, limited and most patients develop chronic disability and require total knee arthroplasty or total hip replacement. Emerging therapies targeting specific cytokines and growth factors in the RA inflammatory cascade offer potent new means of modifying disease activity. Recently, increased concentrations of adipokines, including visfatin, mainly produced by adipocytes in serum and joint synovial fluid, were found in RA patients. Visfatin has important pro-inflammatory and catabolic roles in RA pathogenesis and is now being studied as a potential therapeutic target for RA. Here we discuss the relationship between visfatin and RA and its potential as a therapeutic target for RA.
18957873 Efficacy of biologicals in the treatment of rheumatoid arthritis. a meta-analysis. 2009 Rheumatoid arthritis (RA) is a chronic multisystem disease. A characteristic feature of RA is persistent inflammatory synovitis, usually involving the peripheral joints in a symmetric distribution. The prevalence of RA is approximately 0.8% of the population (range: 0.3-2.1%); women are affected approximately 3 times more often than men. The current therapeutic approach is to start a disease-modifying agent early in the illness to prevent eventual joint damage. Older disease-modifying anti-rheumatic drugs include methotrexate, sulphasalazine and hydroxychloroquine. Newer ones such as leflunomide and cyclosporin are also used. A recent advance in the management of rheumatoid arthritis is the use of biological agents, which block certain key molecules involved in the pathogenesis of the illness. They include tumour-necrosis-factor-alpha-blocking agents such as infliximab, etanercept and adalimumab, the anti-CD-20 agent, rituximab, and CTLA-4 Ig abatacept. The present study was planned with the aim of evaluating the efficacy of such newer biological therapies in refractory RA at various time points. Databases including Medline, Embase and the Cochrane Library were searched for all relevant studies up to January 2007. A total of 26 studies were included in present meta-analysis. The method of DerSimonian and Laird [Control Clin Trials 1986;7:177-188] was used to calculated a pooled odds ratio (OR) for the American College of Rheumatology (ACR) criteria 20, 50 and 70, at 24, 54 and 96 weeks. The overall pooled OR were found to be significantly more than the placebo at all 3 time points for all 3 criteria (ACR 20, 50 70). In conclusion, biologicals as a group are highly effective in the treatment of RA. Biologicals were efficacious both in treatment naïve and methotrexate-refractory patients.
19962619 The Disease Activity Score and the EULAR response criteria. 2009 Nov The Disease Activity Score (DAS), its modified version the DAS28, and the DAS-based European League Against Rheumatism (EULAR) response criteria are well-known measures of disease activity in rheumatoid arthritis (RA). The DAS is a clinical index of RA disease activity that combines information from swollen joints, tender joints, the acute phase response, and general health. The EULAR response criteria classify individual patients as non-, moderate, or good responders, depending on the extent of change and the level of disease activity reached. The DAS, DAS28, and EULAR response criteria have been validated extensively. For daily practice, it has been shown that a tight control strategy, including measurement of disease activity using the DAS and planned adjustment of antirheumatic medication, is an effective strategy for RA. This article summarizes the development and validation of the DAS and DAS28 and their use in clinical trials and practice for the clinician.
19738217 Assessing quality of sleep in patients with rheumatoid arthritis. 2009 Sep We sought to identify instruments assessing sleep quality that measure the domains of sleep applicable to rheumatoid arthritis (RA) patients and are feasible to use and have appropriate reliability, validity, and responsiveness properties. A systematic review of sleep instruments was conducted. In particular, domains related to sleep that were assessed in the instruments were identified and evaluated. Feasibility characteristics and psychometric properties of instruments were reviewed. At OMERACT 9, the preparatory work was described at the plenary session of the Patient Perspective Workshop, and the tasks of 3 breakout groups in ranking and scoring the domains and sleep instruments were outlined. Each breakout group considered different aspects of sleep: sleep domains, feasibility, and psychometric properties. The rapporteur for each breakout group reported back to the plenary on the domains and sleep instruments that achieved the highest rank/score. The systematic review identified 45 sleep instruments of interest. Based on these instruments, 14 domains of sleep were identified. The top ranked domains were: Sleep Adequacy (1), Sleep Maintenance (2), Sleep Initiation (3) and Daytime Functioning (4). The top ranked instruments on feasibility were: Athens Insomnia Scale (2.3), Medical Outcome Study (MOS) Sleep (4.0), Insomnia Severity Index (4.9), and Women's Health Insomnia Rating Scale (5.5). The highest scored instruments on psychometric properties were: Athens Insomnia Scale (13.6), Sleep Assessment Questionnaire (13), Pittsburgh Sleep Diary (12), and MOS Sleep (11). Sleep domains have been reviewed, and several sleep instruments have been identified. These instruments should be considered for use in planned clinical trials of RA patients to assess their applicability.
19491913 Tyrosine kinases as targets for the treatment of rheumatoid arthritis. 2009 Jun As critical regulators of numerous cell signaling pathways, tyrosine kinases are implicated in the pathogenesis of several diseases, including rheumatoid arthritis (RA). In the absence of disease, synoviocytes produce factors that provide nutrition and lubrication for the surrounding cartilage tissue; few cellular infiltrates are seen in the synovium. In RA, however, macrophages, neutrophils, T cells and B cells infiltrate the synovium and produce cytokines, chemokines and degradative enzymes that promote inflammation and joint destruction. In addition, the synovial lining expands owing to the proliferation of synoviocytes and infiltration of inflammatory cells to form a pannus, which invades the surrounding bone and cartilage. Many of these cell responses are regulated by tyrosine kinases that operate in specific signaling pathways, and inhibition of a number of these kinases might be expected to provide benefit in RA.
19022481 Systemic nonarticular manifestations of rheumatoid arthritis: focus on inflammatory mechan 2009 Oct OBJECTIVE: Extra-articular ("nonarticular") manifestations of rheumatoid arthritis (RA) are common and greatly affect physical and emotional health, as well as prognosis, including survival. Several plausible mechanisms have been advanced for many nonarticular manifestations but there is increasing evidence that pro-inflammatory cytokines (eg, tumor necrosis factor-alpha [TNF-alpha], interleukin [IL]-1, and IL-6) are also involved. The purpose of this review is to provide a concise appraisal of recent studies investigating the involvement of inflammatory cytokines in the pathogenesis of nonarticular RA manifestations. METHODS: A Medline search for articles published between January 1995 and October 2007 was conducted using the following keywords: rheumatoid arthritis, anemia, cardiovascular, atherosclerosis, bone loss, osteopenia, osteoporosis, pulmonary, thrombocytopenia, lymphadenopathy, keratoconjunctivitis sicca, uveitis, scleritis, keratitis. The review focused on articles describing a potential role of inflammatory mediators in these conditions. RESULTS: Studies of many nonarticular manifestations strongly implicate pro-inflammatory cytokines and specific mechanisms by which these mediators are likely to act have even been elucidated. The inflammatory cytokines implicated are numerous but particularly include members of the TNF family and the interleukins, particularly IL-1 and IL-6. In bone loss, activated T-cells have been shown to express pro-inflammatory cytokines (eg, TNF, IL-1, IL-7, and IL-17) that differentially upregulate and downregulate mechanisms that mediate the balance between bone resorption and formation. Cytokine-mediated inflammation has also been implicated, for example, in the early stages of atherogenesis and this may explain the observed increase in cardiovascular disease among patients with RA. However, for some nonarticular manifestations, the association with pro-inflammatory cytokines has been less firmly established and potential mechanisms are more speculative. CONCLUSIONS: Overall, further research in this area will add to our understanding of the mechanisms of extra-articular manifestations in RA patients. These insights should allow clinicians to select therapies to better match the spectrum of joint disease and nonarticular manifestations in individual patients. This may be particularly relevant for newer biologic agents with specific inhibitory effects on cytokines such as TNF-alpha and IL-6.
19223022 Biomechanical effects of inflammatory diseases on bone-rheumatoid arthritis as a paradigm. 2009 Jul Inflammatory diseases, such as rheumatoid arthritis (RA), influence the bone remodelling process and increase the risk of fracture. Bone can be viewed as a composite material comprising of two phases: the organic phase, constituted predominantly by collagen type I, and the mineral phase, composed primarily by calcium phosphate, in the form of mineral crystals. The mineral component confers bone with strength and stiffness while the organic phase is responsible for bone toughness and ductility and acts as a scaffold for the mineralisation process. The efficacy of bone as a structural material depends on the balance between these different bone components and their biomechanical properties. The main determinants of mechanical properties of bone are the amount of mineral, the collagen content, the orientation of the collagen fibers and minerals and the accumulation of microcracks in the bone matrix. In a mice model of arthritis mechanical testing has shown that arthritic femurs have a significantly lower Young's modulus, yield stress and work until ultimate stress. This evidence suggests that one of the major explanations for the increased fracture risk in RA is related to the changes on bone components induced by inflammation that result in compromised biomechanical properties.
19449019 [Anti-CD20 therapy in rheumatoid arthritis]. 2009 Jul The anti-CD20 antibody Rituximab was the first B-cell-specific therapy approved for the treatment of rheumatoid arthritis patients. The basis for its approval in 2006 was the REFLEX study, which examined the administration of 1000 mg Rituximab at 2-week intervals combined with Methotrexat compared with placebo in patients with poor response to TNF-inhibitors in terms of all relevant clinical parameters. Radiological data show that Rituximab is capable of effectively arresting joint destruction. The treatment was well tolerated. The most common side effect, seen in up to 35% of patients, was infusion reactions, particularly during initial Rituximab administration. This could be reduced by approximately 30% with the use of steroid premedication. The serious infection rate in this randomised trial was slightly increased compared with the placebo group, as would also be expected for other biologicals. Data on re-treatment is currently available for up to five treatments and show sustained and/or improved efficacy with continued good tolerance.
20381401 Characteristics and development of therapeutic patient education in rheumatoid arthritis: 2010 Oct OBJECTIVE: The aim of this study is to point out the recent characteristics and developments of therapeutic patient education (TPE) in rheumatoid arthritis through an analysis of the international articles published from 2003 to 2008. METHOD: Studies were selected from major databases, using the following keywords: rheumatoid arthritis, patient education, self-management, programs. Three authors independently reviewed each study and selected the data using the patient education research categories (PERC). Articles consistently related to patient education in rheumatoid arthritis (37 among 109) were included. RESULTS: The selected articles have been published in 23 scientific journals. The majority of them concern TPE for adult patients with rheumatoid arthritis. TPE is delivered in several structures and group education represents the most widespread educational strategy mainly provided by a multiprofessional team. There are two types of programs: educational, aiming to make the patient competent in the daily management of his disease and psycho-educational ones, aiming to improve coping and to decrease stress, anxiety and depression. Twenty-eight studies show the effectiveness of TPE on the basis of bio-clinical, educational, psychosocial, economical criteria, but the majority of these positive results are observed in short-term. Barriers to TPE are linked to cultural and socio-economic factors. CONCLUSION: A large number of studies still assess the positive effects of TPE. Nowadays, the problems of short-term efficacy of TPE and the cultural and social barriers to this practice have become a major issue for research.
20142814 Targeting cardiovascular risk in rheumatoid arthritis: a dual role for statins. 2010 Mar Rheumatoid arthritis (RA) is a prototypical immune-mediated inflammatory disease that is characterized by increased cardiovascular morbidity and mortality, independent of the traditional risk factors for cardiovascular disease. The chronic inflammatory state--a hallmark of RA--is considered to be a driving force for accelerated atherogenesis. Consequently, aggressive control of RA disease activity is thought to be instrumental for cardiovascular risk reduction. Currently, statin-mediated reduction of LDL-cholesterol levels is considered to be the cornerstone of cardiovascular disease prevention. In addition to their lipid-lowering capabilities, statins exert immunomodulatory effects, which could be of dual benefit in the treatment of RA. Guidelines on the reduction of cardiovascular risk in patients with RA are lacking, however, largely owing to the absence of data from randomized controlled trials. This Review focuses on the pathophysiology of cardiovascular events in RA, as well as the need to adjust cardiovascular risk engines to better-accommodate the impact of chronic inflammatory disease over and above the established risk factors to predict cardiovascular risk in patients with RA.
21507802 Nonpharmacological interventions for the treatment of rheumatoid arthritis: a focus on min 2010 Apr Rheumatoid arthritis (RA) is a chronic, autoimmune disease that affects approximately 1.3 million Americans. It is characterized by inflammation of the joints, most often affecting the hands, hips, and knees. Presently, there is no cure, and the commonly used pharmacological therapies are not always effective and have significant side effects, especially when used long term. Consequently, there is a need for alternative treatments for RA. Mind-body medicine (MBM), which uses the mind to affect disease processes, is a promising area for many pathological conditions, especially autoimmune disorders like RA. In this review, we highlight the basis for psychological-based interventions for the treatment of RA. The notion that the mind has an impact on immune function and several processes that underpin the pathophysiology of RA is well established. Correspondingly, there are several lines of evidence to indicate that psychological-based interventions can favorably affect these processes. Clinical trials of MBM in RA have most commonly assessed outcomes such as pain, functional disability, psychological status, coping abilities, self-efficacy, and joint involvement. Across studies, statistically significant improvements were found for all outcomes, though the clinical significance of these changes is open to interpretation. Given that the RA patients included in these studies had generally maximized the use of pharmacological options, any additional therapeutic benefit may be considered significant. Patients with a history of depression appear to exhibit heightened responsiveness to MBM, and this is a group that should be preferentially targeted. Based on the current evidence, MBM can be recommended as an adjunct to conventional therapy to enhance treatment response and possibly reduce the use of more risky pharmacological therapies.