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Search for: rheumatoid arthritis    methotrexate    autoimmune disease    biomarker    gene expression    GWAS    HLA genes    non-HLA genes   

ID PMID Title PublicationDate abstract
24080116 Burden of disease in treated rheumatoid arthritis patients: going beyond the joint. 2014 Feb OBJECTIVE: The disease burden in rheumatoid arthritis (RA) extends beyond the joint. This article evaluates the physical and psychosocial extra-articular burden of treated RA and relationships among diverse disease manifestations. METHODS: MEDLINE searches identified papers published in English from January 2003 to December 2012 that evaluated systemic complications and psychosocial aspects associated with RA. Preference was given to studies with randomized cohorts and large (>100) sample sizes. Of 378 articles identified in the initial search, 118 were selected for inclusion. RESULTS: RA is associated with multiple comorbidities and psychosocial impairments, including cardiovascular disease, osteoporosis, interstitial lung disease, infection, malignancies, fatigue, depression, cognitive dysfunction, reduced work performance, work disability, and decreased health-related quality of life. The etiology of the extra-articular burden may reflect the systemic inflammation and immune system alteration associated with RA, metabolic imbalances and side effects related to treatment, or the influence of comorbidities. Strategies that may help to reduce the extra-articular disease burden include personalized medicine and the potential introduction of treatments with new mechanisms of action. CONCLUSION: Despite improvements in treating joint disease, the extra-articular burden in RA remains substantial, encompassing multiple comorbidities and psychosocial impairments.
23325096 Toll-like receptor polymorphisms and rheumatoid arthritis: a systematic review. 2014 Jan The aim of this study was to determine whether toll-like receptor (TLR) polymorphisms confer susceptibility to rheumatoid arthritis (RA) and influence the clinical characteristics of RA. The authors conducted a systematic review on associations between TLR polymorphisms and RA susceptibility and clinical findings. Meta-analysis was performed if at least three comparisons of an issue were available. A total of 14 studies were included in this systematic review, which included European and Asian studies. Meta-analysis of five European studies showed no association between the TLR4 Asp299Gly (rs4986790) polymorphism and RA (OR for the minor allele = 0.907, 95% CI = 0.755-1.088, p = 0.291). Furthermore, none of these studies found any association between the polymorphism and clinical characteristics. A significant difference between TLR9 rs187084 allele frequencies in RA patients and controls was found in one Turkish study (p = 0.003), and a moderate association between RF positivity and TLR8 rs5741883 was found in an European study (p = 0.001). The numbers of guanine-thymine [(GT)n] repeats in intron II of the TLR2 gene were found a significantly higher S-allele frequency in Korean patients with RA than in controls (30.3 vs. 23.0 %, p = 0.03). This meta-analysis shows lack of an association between the TLR4 Asp299Gly polymorphism and RA. However, our finding suggests the possibility that TLR polymorphisms are associated with the development and clinical characteristics of RA. Because of a paucity of data of the TLR polymorphisms, case-control studies are required to determine whether TLR2, 4, 8, 9 polymorphisms contribute to RA susceptibility or severity in more than 2,000 patients and controls.
24134815 [The rheumatoid hand]. 2013 Dec Rheumatoid arthritis usually affects the hand (90%). Without treatment, joint damages and deformities lead to loss of the ability to grip, grasp, and pinch, often leaving the patient unable to perform the activities of daily living. Early treatment with DMARDs ± physical therapy is the best way to control the disease and prevent deformity, as well as disability, which often occurs when joints get damaged. Two decades later dramatic advances have been made in the medical therapy of RA with the expanded range of effective disease-modifying antirheumatic drugs. When a patient with RA develops joint damages in the hand or wrist that are unresponsive to medical management and injections therapy, surgical intervention may be necessary. Optimal care involves a team approach among the patient involving rheumatologists, physical therapists and hand surgeons. Patients with RA should be closely monitored in order to detect joint damages necessitating physical therapist or hand surgeon consultation.
24129129 The role of low-dose glucocorticoids for rheumatoid arthritis in the biologic era. 2013 Jul In rheumatoid arthritis (RA), low-dose glucocorticoid (GC) therapy has a well-established effect on disease activity. Particularly in early RA, robust evidence demonstrates that GC treatment in association with standard disease-modifying anti-rheumatic drugs (DMARDs) is effective in inducing high remission rates, earlier and more persistently. Despite international recommendations that discourage long-term concomitant GC use, the majority of the clinical trials and observational registries on biologic agents include a high proportion (up to 80%) of patients in treatment with GC. From an analysis of the literature, a substantial lack of reliable information about the efficacy of GC in association with biologic agents emerges; in particular, the role of GC co-therapy in sustaining remission after biological therapy discontinuation remains to be clarified. Given the increasing prevalence of patients in sustained remission, a rational discontinuation strategy should include low-dose GCs in the experimental design to elucidate their role in inducing and maintaining biologic-free remission, for efficacy, safety and pharmacoeconomic considerations.
23981743 Th17 Cells in Immunopathogenesis and treatment of rheumatoid arthritis. 2013 Jun Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by the sequestration of various leukocyte subpopulations within both the developing pannus and synovial space. The chronic nature of this disease results in inflammation of multiple joints, with subsequent destruction of the joint cartilage and erosion of bone. Identification of T helper (Th)17 cells led to breaking the dichotomy of the Th1/Th2 axis in immunopathogenesis of autoimmune diseases such as RA, and its experimental model, collagen-induced arthritis (CIA). Th17 cells produce cytokines, including interleukin (IL)-17, IL-6, IL-21, IL-22 and tumor necrosis factor (TNF)-α, with pro-inflammatory effects, which appear to have a role in immunopathogenesis of RA. Regarding the wide ranging production of pro-inflammatory cytokines and chemokines by Th17 cells, it is expected that Th17 cell could be a potent pathogenic factor in disease immunopathophysiology. Thus the identification of effector mechanisms used by Th17 cells in induction of disease lesions may open new prospects for designing a new therapeutic strategy for treatment of RA.
24606324 Positron emission tomography/computed tomography imaging and rheumatoid arthritis. 2014 Mar Rheumatoid arthritis (RA) is a phenotypically heterogeneous, chronic, destructive inflammatory disease of the synovial joints. A number of imaging tools are currently available for evaluation of inflammatory conditions. By targeting the upgraded glucose uptake of infiltrating granulocytes and tissue macrophages, positron emission tomography/computed tomography with fluorine-18 fluorodeoxyglucose ((18) F-FDG PET/CT) is available to delineate inflammation with high sensitivity. Recently, several studies have indicated that FDG uptake in affected joints reflects the disease activity of RA. In addition, usage of FDG PET for the sensitive detection and monitoring of the response to treatment has been reported. Combined FDG PET/CT enables the detailed assessment of disease in large joints throughout the whole body. These unique capabilities of FDG PET/CT imaging are also able to detect RA-complicated diseases. Therefore, PET/CT has become an excellent ancillary tool to assess disease activity and prognosis in RA.
23574521 The genetic architecture of rheumatoid arthritis: from susceptibility to clinical subpheno 2013 Rheumatoid Arthritis (RA) is the most common chronic inflammatory disease of the joints and is characterized by a complex genetic architecture. In recent years, a substantial advance has been performed in the identification of the genes that increase the risk to develop RA. Genome-Wide Association Studies (GWAS) have allowed the characterization of more than 40 new susceptibility genes and the confirmation of a marked differential genetic background between patients expressing anti-cyclic citrullinated peptide antibodies (ACPA, approximately 80% of all RA patients) and ACPA negative RA patients. GWAS have also confirmed the existence of a common genetic basis between RA and other autoimmune diseases and the overrepresentation of specific biological pathways like antigen presentation and TNF signaling. Dense genotyping analysis has also allowed the detailed characterization of the different association signals within the HLA region, the strongest risk locus for RA. In the present manuscript, we also review the most recent advances in the genetics of clinically relevant subphenotypes in RA which are the response to treatment and the severity of the disease. In the next years the increasing ability to characterize the DNA variation and the availability of well characterized patient cohorts will be critical to translate genetic information into the much awaited personalized medicine in RA.
24934191 Defining populations at risk of rheumatoid arthritis: the first steps to prevention. 2014 Sep Preventing disease is a public health priority. In recent years, this focus has evolved to include noncommunicable chronic diseases such as cardiovascular disease and diabetes mellitus but is novel in rheumatic diseases such as rheumatoid arthritis (RA). In order to prevent RA, the 'at-risk' populations need to be defined. To date, a number of studies have attempted to clarify our understanding of these cohorts and how they could be identified. Suggested terminology has now been published to define individuals who might go on to develop RA. This Review considers categories of these 'at-risk' individuals, with a focus on those with systemic autoimmunity. Trials in very early RA demonstrate that disease outcomes can be reduced with early intervention. These principles are widely accepted in other diseases such as type 1 diabetes mellitus, in which steps have been taken to prevent disease in genetically predisposed individuals. Large population-based studies provide insights into potential interventions for RA prevention. By quantifying risk in different populations, the prospect of preventing this disease is feasible.
23257071 The role of glycoprotein 96 in the persistent inflammation of rheumatoid arthritis. 2013 Feb 1 The 96-kDa glycoprotein (gp96) is an endoplasmic reticulum (ER) resident molecular chaperone. Under physiologic conditions, gp96 facilitates the transport of toll-like receptors (TLRs) to cell or endosomal membranes. Under pathologic circumstances such as rheumatoid arthritis, gp96 translocates to the cell surface and extracellular space, serving as an endogenous danger signal promoting TLR signaling. Macrophages play a central role in regulating innate and adaptive immunity, and are the major source of proinflammatory cytokines and chemokines in rheumatoid arthritis (RA). Macrophage numbers in the sublining of RA synovial tissue correlate with clinical response. This review focuses on the recent findings that implicate gp96 induced macrophage activation mediated through TLR signaling in the pathogenesis of RA and provides insights concerning the targeting gp96 and the TLR signaling pathway as therapeutic approaches for patients with RA and possibly other chronic inflammatory conditions.
24783461 Increased cardiovascular risk in patients with rheumatoid arthritis: an overview. 2014 Apr Patients with established rheumatoid arthritis (RA) have a higher cardiovascular morbidity and mortality in comparison with the general population. It is considered to be an independent risk factor for cardiovascular disease. The purpose of this article is to describe the mechanisms responsible for accelerated atherogenesis in RA patients and to give an overview of the effects of different RA therapies (methotrexate, TNF antagonists and other biologicals).
23318734 Impact of microRNAs on the understanding and treatment of rheumatoid arthritis. 2013 Mar PURPOSE OF REVIEW: It is becoming more and more obvious that epigenetic processes influence the development of rheumatic diseases as strongly as the genetic background. Research on the role of microRNAs (miRNAs) in rheumatic diseases, and especially in rheumatoid arthritis (RA), has been very active for the past 5 years. Most studies have reported the aberrant expression of miRNAs in the circulation or joint tissues, and the pathogenic role of a few of them has been investigated in the experimental models. RECENT FINDINGS: As inflammation and joint damage are the main hallmarks of RA, we focused on the three miRNAs, miR-146a, miR-155 and miR-223, whose functions have been studied in both the processes and the pathogenic role investigated in the experimental models. SUMMARY: Focusing on the role of miR-146a, miR-155 and miR-223 in RA pathogenesis emphasizes the intertwined relationships between bone homeostasis and immunity, and the prominent role of monocytes in RA. Studying the miRNAs in RA will shed light on the pathological processes and help in identifying novel drug candidates and biomarkers.
24089023 The importance of early treatment for the prognosis of rheumatoid arthritis. 2013 Chronic synovial inflammation in rheumatoid arthritis (RA) leads to progressive damage to articular cartilage and bone, ultimately resulting in disability. Therefore, control of the articular inflammation is of great importance to prevent joint damage. A variety of disease-modifying antirheumatic drugs (DMARDs) are available for RA patients. Conventional synthetic DMARDs, and in particular biological DMARDs, have been shown to effectively inhibit joint destruction in RA. Longitudinal assessments of radiographic changes in patients with RA in clinical trials and in large patient registries have clearly shown that delays in the initiation of DMARD therapy results in significantly increased progression of joint damage. Patients started early on DMARDs had significantly lower radiographic damage progression than patients initiating DMARD treatment later. These effects were maintained for several years, suggesting that early in the development of RA a therapeutic window of opportunity exists in which DMARD therapy decisively influences the long-term prognosis. Therefore, to improve the clinical outcome of RA, our efforts should be directed towards diagnosing RA earlier and introducing DMARD therapy immediately after the diagnosis has been made.
23574522 Achievements and challenges of proteomics in the study of rheumatoid arthritis. 2013 Effective management of Rheumatoid Arthritis (RA) is being hampered by the difficulties for its early diagnosis and the heterogeneity of the disease. Although early intervention can result in disease remission, it requires early diagnosis, and current diagnostic tests are not sufficiently accurate or sensitive in the early stages of RA. Therefore, research efforts are increasingly focused on gaining knowledge about RA pathogenesis, and also on the discovery of novel biological markers that enable early diagnosis and stratification of the disease, and thus the implementation of targeted therapies. Ongoing research includes the emergence of novel approaches for the characterization of molecules that play a role in RA, such as genomic, proteomic and metabolomic technologies. These techniques, coupled with sophisticated statistical methods, permit the simultaneous analysis of multiple targets, and have become very powerful tools in RA research both for etiopathogenesis studies and biomarker discovery. It is believed that proteomics will soon provide a much-needed novel therapeutic approach to treating RA. This chapter will focus on the utility of Proteomics in RA research to enable a better understanding of the disease process, and to provide novel protein biomarkers useful for early diagnosis, prognosis and the application of tailored treatments.
23192911 The risk of infections associated with rheumatoid arthritis, with its comorbidity and trea 2013 Jan RA is known to be associated with an increased risk of serious infection. Even more than 50 years ago, observational studies showed a greater than 2-fold increased risk of serious infection in RA. This was reinforced by various subsequent cohort studies. The elevated susceptibility of patients with RA can be explained by the pathobiology of the disease itself, the impact of chronic comorbid conditions, as well as sequelae of immunosuppressive treatment. It has been suggested that premature ageing of the immune system in RA contributes to weakened protection against infectious organisms. In addition, chronic comorbid conditions such as diabetes or chronic lung or kidney disease, disease-related functional disability, as well as lifestyle factors such as smoking, increase the risk in individual patients. For a long time glucocorticoids (GCs) have been used as potent immunosuppressive drugs in RA. There is evidence that they increase the risk of serious infections up to 4-fold in a dose-dependent manner. TNF-α inhibitors increase the serious infection risk up to 2-fold. They have, however, the potential to outweigh their risk when higher GC doses can be tapered down. If patients need higher dosages of GCs in addition to treatment with biologic agents, their risk of infection is substantial. This combination should be used carefully and, if possible, avoided in patients with additional risk factors such as older age or comorbid conditions.
23901448 Treat-to-target: a tailored treatment approach to rheumatoid arthritis. 2013 Mar 28 In contrast to articles and books written about rheumatoid arthritis (RA) two or more decades ago that largely focused on 'coping' with the disease, there have been significant developments in the treatment of RA over the past 10 years. Patients can now be diagnosed and treated and expect to live functional lives, with less likelihood of experiencing the associated joint damage and disability. An important goal of RA therapy has shifted to initiate treatment early and aggressively, with frequent assessment and a target to achieve remission as quickly as possible. This 'treat-to-target' concept has been endorsed to maximise long-term health-related quality of life through control of symptoms, prevention of structural damage, normalisation of function and social participation. This article will look at therapies and strategies for the treatment of RA. It will also discuss a treatment algorithm for rheumatoid arthritis tailored to the individual patient's disease activity status.
24443794 Understanding IFNλ in rheumatoid arthritis. 2014 Jan 21 Unraveling the mechanisms underlying the inflammatory response in rheumatoid arthritis is crucial in order to better understand the disease and to develop novel therapeutic approaches. Although the effect of type I interferons on fibroblasts and in the context of rheumatoid arthritis has been described for some time, little is known on the effects of the type III interferons, also known as IFNλ. In a previous issue, Xu and colleagues demonstrate that one of the members of the IFNλ family, IFNλ1, enhances Toll-like receptor expression and consequently promotes the production of proinflammatory cytokines known to be involved in initiating and maintaining the inflammatory responses in rheumatoid arthritis.
24219036 Update on methotrexate as the anchor drug for rheumatoid arthritis. 2013 Methotrexate has become the "anchor drug" for rheumatoid arthritis (RA), taken by many more patients than any other disease modifying anti-rheumatic drug (DMARD) or biological agent. Methotrexate has greater efficacy and effectiveness than any other non-biologic DMARD, and greater tolerability and safety than other DMARDs. The efficacy of methotrexate is comparable to biologic agents in parallel clinical trials of DMARD-naïve patients. Adequate responses to methotrexate monotherapy or combinations with other non-biologic DMARDs are seen in about two- thirds of patients with RA in usual care. The most efficacious treatments for RA reported in the rheumatology literature are seen in strategy trials with methotrexate as the anchor drug, without any biologic agent. Interpretation of significantly lower radiographic progression between methotrexate and biologic agents in clinical trials is over- stated regarding clinic consequences. The admonition to patients to refrain entirely from consumption of alcohol while taking methotrexate may be unnecessary. Accurate information concerning methotrexate as the anchor drug for RA should lead to better understanding of optimal use and better to patient outcomes in usual clinical care.
25315196 Cardiovascular risk and the use of biologic agents in rheumatoid arthritis. 2014 Nov Although patients with rheumatoid arthritis (RA) are recognized to be disproportionately impacted by cardiovascular disease (CVD), effective approaches of primary and secondary CVD prevention have not been well defined in this population. Given their robust disease-modifying potential and effects on both pro-inflammatory and pro-atherogenic pathways, there has been substantial speculation that biologic treatments may serve as a means of providing highly effective RA disease control while simultaneously reducing CVD risk in this high risk group. In this review, we examine available evidence relevant to the associations of approved biologic treatments with CVD outcomes in the context of RA.
24457026 Mechanisms of endothelial dysfunction in rheumatoid arthritis: lessons from animal studies 2014 Jan 24 Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease characterized by articular and extra-articular manifestations involving cardiovascular diseases (CVDs), which account for 30% to 50% of all deaths. In patients with RA, atherosclerosis lesions occur earlier and have a more rapid evolution than in the general population. Beyond mortality, the impact of CVD on quality of life, combined with the associated increase in health-care costs, renders CVD in RA a major public health problem. Recent studies showed that patients with RA are characterized by the presence of endothelial dysfunction (ED), which is recognized as a key event in the development of atherosclerosis. By definition, ED is a functional and reversible alteration of endothelial cells, leading to a shift of the actions of the endothelium toward reduced vasodilation, proinflammatory state and proliferative and prothrombotic properties. Although the improvement of endothelial function is becoming an important element of the global management of patients with RA, the mechanistic determinants of ED in RA are still poorly understood. Animal models of RA provide the unique opportunity to unravel the pathophysiological features of ED in RA. The present review summarizes the available data on mechanisms underlying ED in animal models of RA and proposes attractive prospects in order to discover novel therapeutic strategies of RA-associated ED.
23963816 Correlates of physical activity in adults with rheumatoid arthritis: a systematic review. 2014 Aug BACKGROUND: Physical activity (PA) is an important component in the management of Rheumatoid Arthritis (RA). To date the correlates of PA have not been thoroughly investigated in the RA population. The aim of this systematic review was to determine the correlates of PA in the adult RA population. METHODS: A search of Medline, EMBASE, AMED, CINAHL plus, Pubmed, Web of Science, and the Cochrane Library was conducted. A manual search of reference lists was conducted to compliment the electronic search. Ten studies fulfilled the inclusion criteria and were assessed for methodological quality. RESULTS: Results determined correlates in 4 categories: sociodemographic, physical, psychological and social variables. The variables varied greatly and were inconsistently studied. Changes were noted from a previous review in 2005 in relation to the association between certain variables and PA, including age, gender, disease duration, pain, exercise beliefs and social support. CONCLUSIONS: Positive associations with PA were found for motivation, self-efficacy, health perception, and previous PA levels. Negative associations were found for fatigue, a coerced regulation style and certain physiological variables. In addition differences between correlates of PA in the adult RA population and other chronic disease and healthy adult populations have been demonstrated.