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ID PMID Title PublicationDate abstract
23439035 The ascent of acetylation in the epigenetics of rheumatoid arthritis. 2013 May Genome-wide association studies have shown that genetic polymorphisms make a substantial but incomplete contribution to the risk of developing rheumatoid arthritis (RA). Efforts to understand the nongenetic contributions to RA disease susceptibility have recently focused on the study of epigenetic mechanisms, namely modifications of DNA and histones, which are subject to environmental influences and regulate gene expression. A surprising theme emerging from studies of the enzymes responsible for these epigenetic modifications, particularly histone deacetylases, is that they regulate inflammatory activation of cell populations relevant to RA through independent, direct, and dynamic interactions with nonhistone proteins. Herein, we highlight studies, the findings of which collectively suggest that revisiting the original definition of epigenetics, conceived some 70 years ago, might advance our interpretation of DNA and histone modifications with regard to gene expression and clinical outcome in RA. Such an approach could also facilitate the development of strategies to target these epigenetic modifications in the clinic.
24103529 Outcome measures in rheumatoid arthritis randomised trials over the last 50 years. 2013 Oct 9 BACKGROUND: The development and application of standardised sets of outcomes to be measured and reported in clinical trials have the potential to increase the efficiency and value of research. One of the most notable of the current outcome sets began nearly 20 years ago: the World Health Organization and International League of Associations for Rheumatology core set of outcomes for rheumatoid arthritis clinical trials, originating from the OMERACT (Outcome Measures in Rheumatology) Initiative. This study assesses the use of this core outcome set by randomised trials in rheumatology. METHODS: An observational review was carried out of 350 randomised trials for the treatment of rheumatoid arthritis identified through The Cochrane Library (up to and including September 2012 issue). Reports of these trials were evaluated to determine whether or not there were trends in the proportion of trials reporting on the full set of core outcomes over time. Researchers who conducted trials after the publication of the core set were contacted to assess their awareness of it and to collect reasons for non-inclusion of the full core set of outcomes in the study. RESULTS: Since the introduction of the core set of outcomes for rheumatoid arthritis, the consistency of measurement of the core set of outcomes has improved, although variation in the choice of measurement instrument remains. The majority of trialists who responded said that they would consider using the core outcome set in the design of a new trial. CONCLUSIONS: This observational review suggests that a higher percentage of trialists conducting trials in rheumatoid arthritis are now measuring the rheumatoid arthritis core outcome set. Core outcome sets have the potential to improve the evidence base for health care, but consideration must be given to the methods for disseminating their availability amongst the relevant communities.
24315048 Early rheumatoid arthritis: the performance of the 2010 ACR/EULAR criteria for diagnosing 2013 Aug New classification criteria for rheumatoid arthritis (RA) were presented by the American College of Rheumatology (ACR) and the European League Against Rheumatism (EULAR) in 2010, aiming for early identification of patients at risk of developing persistent and erosive arthritis. Since their publication, the criteria have been extensively validated against several reference standards, but there is still debate regarding how the criteria should be implemented in studies and clinical care. We present an overview of the published validation studies and discuss the strengths and limitations of the classification criteria, as well as whether the criteria are ready for diagnostic purposes in clinical practice.
24468938 Risk estimation in rheumatoid arthritis: from bench to bedside. 2014 Mar The prognosis for patients with rheumatoid arthritis (RA) who were diagnosed in the years since 2010 is much better than for individuals who were diagnosed with the disease 20 years ago. This improvement in the long-term outcome of disease is the result of earlier initiation of therapy, disease-activity-guided modification of treatment and the availability of new, and effective, drugs. Nonetheless, current treatment strategies remain population-based, rather than individualized. Decision-making processes relevant to the provision of individualized treatment require appropriate prognostication with regard to a number of variables. Here, the methods available to evaluate the performance of predictive models are discussed. In addition, I highlight the advances in risk estimation that have been made concerning three treatment decisions relevant to the management of RA that are made daily in the clinic: when to initiate treatment with DMARDs in patients in the early stages of arthritis; the ideal intensity of initial treatment; and the likely responsiveness of the patient to a particular therapy. Apart from a model predicting the development of RA, the majority of prognostic tools derived in arthritis and RA are not accurate or not validated. Hence, personalized treatment decisions in arthritis and RA are still far from bedside.
24652004 DNA methylation: roles in rheumatoid arthritis. 2014 Sep Rheumatoid arthritis (RA) is an immune-mediated disease of unknown cause that primarily affects the joints and ultimately leads to joint destruction. In recent years, the potential role of DNA methylation in the development of RA is raising great expectations among clinicians and researchers. DNA methylation influences diverse aspects of the disease and regulates epigenetic silencing of genes and behavior of several cell types, especially fibroblast-like synoviocytes (FLS), the most resident cells in joints. The activation of FLS is generally regarded as a key process in the development of RA that actively results in the promotion of ongoing inflammation and joint damage. It has also been shown that aberrant DNA methylation occurs in the pathogenesis of RA and contributes to the development of the disease. Recently, there has been an impressive increase in studies involving DNA methylation in RA. In this paper, we consider the role of DNA methylation in the development of RA.
23790244 What do we know about the safety of corticosteroids in rheumatoid arthritis? 2013 Sep BACKGROUND: Clear information is still lacking on the safety of corticosteroids (GCs) therapy in RA despite six decades of clinical experience. SCOPE: We performed a literature search in Ovid MEDLINE from January 2000 to December 2012. Our Population Intervention Comparator Outcomes (PICO) strategy search was: rheumatoid arthritis [Population], corticosteroids or glucocorticoids [Intervention], any comparison [Comparator], adverse effects [Outcome]. Studies were selected if they reported any measure of association between GCs intake and potential adverse effects in RA patients. FINDINGS: We identified 1030 papers and selected for analysis 26 observational studies and six systematic reviews. The major side effects of GCs in RA are bone loss, risk of cardiovascular events and risk of infections as evidenced by large observational studies and not necessarily RCTs. Others associations were reported with herpes zoster, tuberculosis, hyperglycemia, cutaneous abnormalities, gastrointestinal perforation, respiratory infection and self-reported health problems such as cushingoid phenotype, ecchymosis, parchment-like skin, epistaxis, weight gain and sleep disturbance. Other potential adverse effects of GCs were studied but no association was found. These included psychological disorders, dermatophytosis, brain diseases, interstitial lung disease, memory deficit, metabolic syndrome, lymphoma, non-Hodgkin's lymphoma, renal function and cerebrovascular accidents. Most of the evidence emanates from observational researches and the inherent limitations of such data should be kept in mind. CONCLUSION: Recent observational data and systematic reviews suggest that GCs can lead to relatively alarming and burdensome side effects in RA. This is particularly true for patients who have longer term and higher dose therapies. GCs are largely used in RA and knowing their safety profile is essential to improve patients care. The design of new therapeutic strategies intended to minimize the daily dosing of GCs while conserving their beneficial effect should be encouraged.
23961666 [Imaging of rheumatoid arthritis: role of MR imaging and CT]. 2013 Jul An increasing aggressive therapeutic strategy has attracted growing attention to the potentials of MR imaging in the diagnosis, prognostication, and outcome measure of rheumatoid arthritis (RA). In the diagnosis of RA, skeletal destructions are the key to the diagnosis and assessment of long-term prognosis in RA. Marginal bone erosion is still recognized as an important finding in the 2010 RA criteria, and erosions typical of RA are deemed to have prima facie evidence of RA. MR imaging can detect erosions better than radiolography. In this regard, erosions detected by CT are considered to be reference standard to evaluate diagnostic accuracy of erosion in MR imaging and other imaging modalities. Further, to assess therapeutic effect of therapeutic agents involving the control of bone remodeling, CT may be used to evaluate bone formation and improvement of osteoporosis.
24200099 [Therapeutic update in rheumatoid arthritis]. 2013 Dec The treatment of rheumatoid arthritis (RA) was revolutionized by the introduction of the biologics. Their power and their good safety profile have allowed to define new objectives and procedures to reach them; it is the "treat to target" concept. New recommendations were published by EULAR or ACR to obtain the remission as soon as possible. Disease-modifying antirheumatic drugs, in particular the methotrexate (MTX), remain the cornerstone of RA treatment in association with symptomatic treatments. The use of corticosteroids can be necessary to control the disease activity in the waiting time of the DMARDs efficiency or to control a flare. The absence of remission after 3months after initiation of MTX should prompt the rheumatologist to intensify the treatment with biologics. The increasing number of biologics targeting different mechanisms (5 anti-tumor necrosis factor-α, antagonist of interleukine-1 [IL-1] receptor, antagonist of IL-6 receptor, anti-CD20, anti-cytotoxic T-lymphocyte antigen 4) asks the question of the strategy in their prescription. Besides, all the registers or meta-analysis plead in favor of a good safety subject to a moderate prescription and to a greater vigilance. Except the opportunist infections, it is more the comorbidities or the associated treatments such as corticoids or MTX, which would favor the infections than anti-TNFα. There is no indication that biologics may increase the risk of solid cancer compared with a population of RA patients not exposed to anti-TNFα. However, biologics could increase the risk of cutaneous cancers, including melanoma.
25274910 The surgical treatment of rheumatoid arthritis: a new era? 2014 Oct There has been an in increase in the availability of effective biological agents for the treatment of rheumatoid arthritis as well as a shift towards early diagnosis and management of the inflammatory process. This article explores the impact this may have on the place of orthopaedic surgery in the management of patients with rheumatoid arthritis.
24219041 Parenteral methotrexate for the treatment of rheumatoid arthritis. 2013 Methotrexate (MTX) is the anchor treatment for rheumatoid arthritis (RA) and has been very thoroughly studied in many different patient populations, as monotherapy and in combination with various other disease modifying antirheumatic drugs and biologic agents, as they became available. It has a well-established safety and efficacy profile and is the preferred first line agent for RA treatment. Historically, oral (PO) preparations of MTX have been used in the USA with minimal parenteral (subcutaneous, SC, and intramuscular, IM) administration. Several shortages of drug availability in a parenteral form have been possibly one of the reasons for this low level of use. Several studies have looked at the role of parenteral MTX in RA treatment, and these overall demonstrate better tolerability, bioavailability, and possible efficacy of MTX compared with PO preparation.
23053722 Cutaneous necrobiotic conditions associated with rheumatoid arthritis: important extra-art 2013 Jul Rheumatoid arthritis (RA) presents with various skin conditions as extra-articular manifestations. Rheumatoid nodule is the representative specific skin lesion, histologically exhibiting central necrosis (necrobiosis) surrounded by palisaded macrophages, and being further perivascularly infiltrated with inflammatory cells in the outer regions. Also, there are several skin lesions which histologically show necrobiotic conditions with altered connective tissue degeneration. Necrobiosis may be closely associated with the pathogenesis of RA, i.e., collagen degeneration, recruitment of activated neutrophils, production of various cytokines, and vascular injury. On the other hand, rheumatoid nodule is suggested to develop during therapies with certain drugs such as methotrexate and biologics. These findings may be a clue to understanding the pathomechanisms of rheumatoid nodules. This paper describes several necrobiotic conditions associated with RA, and also discusses the possible pathogenesis and differential diagnosis of rheumatoid nodules. Necrobiosis is the major pathologic condition of cutaneous involvement associated with RA.
22885986 Advances in research on animal models of rheumatoid arthritis. 2013 Feb At present, rheumatoid arthritis (RA) is considered a type of autoimmune disease. Its pathology is not certain, and effective drugs with less toxicity have not been established. The establishment and application of animal models are effective methods for RA research, especially using animal models similar to humans. Arthritis is more heterogeneous, and this is an important starting point when discussing animal models for arthritis. Animal models are instrumental in understanding the etiology and pathogenetic mechanisms of RA. Appropriate animal models should be selected according to experiments because they have different traits. Various methods have been applied to induce arthritis in animal experimental models, which have provided important insights into the etiopathogenetic mechanisms of human RA. This review was written to give a broad introduction of the current stage of RA model and hope to offer beneficial help for RA-related research.
23455329 Periodontal disease and rheumatoid arthritis: the evidence accumulates for complex pathobi 2013 May PURPOSE OF REVIEW: This review was conducted to focus on the recent clinical and translational research related to the associations between periodontal disease and rheumatoid arthritis. RECENT FINDINGS: There is a growing interest in the associations between oral health and autoimmune and inflammatory diseases. A number of epidemiologic studies have described associations between rheumatoid arthritis and periodontal disease. Recent clinical studies continue to support these reports, and are increasingly linked with biological assessments to better understand the nature of these relationships. A number of recent studies have evaluated the periopathogenic roles of Porphyromonas gingivalis, the oral microbiome, and mechanisms of site-specific and substrate-specific citrullination. These are helping to further elucidate the interactions between these two inflammatory disease processes. SUMMARY: Studies of clinical oral health parameters, the gingival microenvironment, autoantibodies and biomarkers, and rheumatoid arthritis disease activity measures are providing a better understanding of the potential mechanisms responsible for rheumatoid arthritis and periodontal disease associations. The cumulative results and ongoing studies have the promise to identify novel mechanisms and interventional strategies to improve patient outcomes for both conditions.
23562164 The fibroblast as a therapeutic target in rheumatoid arthritis. 2013 Jun Significant advances have been made in the last 5 years that have finally allowed investigators to start targeting stromal cells such as fibroblasts in inflammatory disease. Rheumatoid arthritis is a prototype inflammatory disease, in which fibroblasts maintain the persistence of inflammation in the joint underpinned by a unique pathological phenotype driven by multiple epigenetic modifications. The step changes that are enabling the development of such therapies are an improved understanding of the mechanisms by which fibroblasts mediate persistence and the discovery of new markers that identify discrete functional subsets of fibroblast cells that have potential as disease-specific therapeutic targets.
25483133 Interleukin-22 and rheumatoid arthritis: emerging role in pathogenesis and therapy. 2015 Mar Rheumatoid arthritis (RA) is a chronic autoimmune disorder characterized by synovial inflammation and resultant progressive joint damage. It has become increasingly evident that cytokines play an important role in the pathogenesis of RA. Interleukin-22 (IL-22) is a member of the IL-10 cytokine family. Recent findings suggest that not only the expression of IL-22 is abnormal both in RA patients and in arthritis mice but also the aberrant IL-22 performs significantly in disease onset of RA. In this paper, we focus on the critical role of IL-22 in RA. Hopefully, the information obtained may lead to a better understanding of the pathogenesis and development of novel therapeutic strategies for this systemic autoimmune disease.
24593197 The role of leukotrienes in immunopathogenesis of rheumatoid arthritis. 2014 Mar Rheumatoid arthritis (RA) is a chronic inflammatory disorder of joints for which there is no strict cure. However, conventional medications can reduce inflammation, relieve pain, and slow joint damage. Leukotrienes are a family of paracrine agents derived from oxidative metabolism of arachidonic acid. Synthesis of lipid mediators and subsequent induction of receptor activity are tightly regulated under normal physiological conditions, so that enzyme and/or receptor dysfunction can lead to a variety of clinical signs and symptoms of disease, such as local pain and tissue edema. In these tissues, immunocompetent cells accumulate at the site of injury, contributing to tissue damage and perpetuation of the disease process. Leukotrienes (often leukotriene B4) as potent chemotactic agents can provoke most signs and symptoms in rheumatoid arthritis by initiating, coordinating, sustaining, and amplifying the inflammatory response, through recruitment of leukocytes. A number of studies have reported that pharmacological modulation in this field can significantly attenuate clinical manifestations associated with different inflammatory pathologies.
25227187 Economics of non-adherence to biologic therapies in rheumatoid arthritis. 2014 Nov Adherence to biologic therapies among patients with rheumatoid arthritis is sub-optimal, with the proportion of adherent patients reported to be as low as 11 %. We found few studies evaluating economic outcomes, including health care costs, associated with non-adherence with biologic therapies. Findings suggest that while higher pharmacy costs drive total health care costs among adherent patients, non-adherent patients incur greater health care utilization including inpatient, outpatient, and laboratory services. Finally, economic factors are important determinants of adherence to biologics in patients with rheumatoid arthritis. Evidence to date has shown that higher out-of-pocket payments have a negative association with adherence to biologics. Furthermore, cost-related non-adherence is a highly prevalent problem in rheumatoid arthritis. Given the high costs of biologics and continued expansion of use in rheumatoid arthritis, there is need for more research to understand the economic implications of adherence to these therapies.
22782500 Coexistence of bronchiectasis and rheumatoid arthritis: revisited. 2013 Apr The presence of bronchiectasis (BR) in patients with rheumatoid arthritis (RA) has been recognized for many decades; nevertheless, little research has been undertaken in this area. It is important to recognize that BR coexistent with RA differs from the other types of BR. The purpose of this descriptive review was to delineate the epidemiology, etiology, risk factors, pulmonary function testing, imaging, prognosis and management of concomitant BR and RA. To inform our study we searched the PubMed, EMBASE, CINAHL, and MEDLINE databases, using combinations of the following key words: computed tomography, lung function tests, rheumatoid arthritis, bronchiectasis, biological agents, and interstitial lung disease. The number of published papers covering this topic is limited, but several relevant conclusions can be drawn. Patients with concomitant RA and BR have worse obstructive airways disease, increased susceptibility to recurrent pulmonary infections, faster lung function decline, and higher mortality, compared with subjects with either RA or BR alone. The use of disease-modifying anti-rheumatic drugs (both biological and non-biological) for RA in RA-BR patients imparts a further challenge in managing these patients. Although there are not any published guidelines on the management of coexisting RA-BR, we have attempted to provide such recommendations, based on the literature review and our experience.
23097394 What is causing my arthritis, doctor? A glimpse beyond the usual suspects in the pathogene 2013 Mar Rheumatoid arthritis (RA) is a common, but heterogeneous, disease. Usually, when it comes to the pathogenesis of RA the physician faces a complex network of cytokines and cells of the immune system-the so-called effector level. However, is this network 'the cause' of the disease? Or is this rather the level most physicians are somewhat familiar with, as modern anti-rheumatic medications are having their targets there? In this review, we are looking beyond the usual culprits from the physician's perspective and discuss how other factors, such as genes, epigenetics, environmental factors, local joint characteristics or processes of aging might influence the clinical phenomenon RA.
24802245 Emerging role of leptin in rheumatoid arthritis. 2014 Sep Numerous studies have suggested the importance of leptin against autoimmune diseases such as systemic lupus erythematosus (SLE), multiple sclerosis (MS) and psoriasis. To summarize our current understanding of the role of leptin in inflammatory responses and rheumatoid arthritis (RA), a systematic review was conducted to assess the discrepancy of leptin in RA and its effect on immunity according to different studies. Recently, emerging data have indicated that leptin is involved in the pathological function of RA, which is common in autoimmune disorders. This review discusses the possible consequences of leptin levels in RA. Blocking the key signal pathways of leptin and inhibiting the leptin activity-like leptin antagonist may be a promising way for potential therapeutic treatment of RA at risk of detrimental effects. However, leptin was increased in patients with RA and may also regulate joint damage. Thus, more understanding of the mechanism of leptin in RA would be advantageous in the future.