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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
22050340 Gene therapy for rheumatoid arthritis: current status and future prospects. 2011 Dec 1 Rheumatoid arthritis (RA) was one of the earliest targets for gene therapy. Since the first clinical trial involving gene therapy in RA was initiated in 1996, eight clinical trials have been conducted assessing gene therapy in RA. Gene therapy has benefited from advances in biologics in terms of the increasing choice of novel, efficient targets to treat RA and also from the optimization of the delivery systems. Several strategies are possible; one of particular interest is local gene therapy directed to rheumatic joints, which avoids systemic vector diffusion. In this review, we discuss (i) gene therapeutic approaches that have been attempted for patients with RA, and (ii) novel strategies that are in development for delivery into patients. We analyze the advantages and disadvantages of the various approaches and how best to optimize them with regard to choosing the most promising vectors and strategies to allow for efficient, long-term, safe delivery of gene therapy in RA.
22819084 Magnetic resonance imaging applications in early rheumatoid arthritis diagnosis and manage 2012 May Early diagnosis and treatment have been recognized as essential for improving clinical outcomes in patients with rheumatoid arthritis (RA). Magnetic resonance imaging (MRI) is a sensitive modality that can assess both inflammatory and structural lesions. MRI can assist in following the disease course in patients treated with traditional disease-modifying antirheumatic drugs and biological therapies both in the clinic and in research trials. Therefore, it is anticipated that MRI becomes the diagnostic imaging modality of choice in RA clinical trials while remaining a useful tool for clinicians evaluating patients with RA.
23273791 Should modern imaging be part of remission criteria in rheumatoid arthritis? 2012 Dec With recent improvements in the treatment of rheumatoid arthritis (RA), remission has become an achievable goal for a large proportion of RA patients, and remission is now a defined target in current RA guidelines. However, studies have shown that progression of radiographic joint damage may occur in clinical remission, regardless of the choice of remission definition. Sub-clinical inflammation detected by modern imaging techniques such as ultrasonography and magnetic resonance imaging is present in the majority of patients in clinical remission, and is associated with progressive joint damage and disease activity flare in these patients. This chapter aims to assess the importance of imaging findings in RA patients in clinical remission and to discuss the possible role of modern imaging in future remission criteria.
21182494 Developing the next generation of monoclonal antibodies for the treatment of rheumatoid ar 2011 Apr Rheumatoid arthritis is one of the commonest autoimmune diseases affecting 0.8% of the population. Over the last decade the treatment of this chronic disease has been revolutionized by the use of monoclonal antibodies and fusion proteins, targeting molecules like tumour necrosis factor alpha. Nevertheless, approximately one-third of subjects fail to respond to these therapies and therefore significant unmet medical need remains. Following a decade of use, clinical, government and regulatory agency expectations have changed for new antibodies therapies entering this highly competitive area. In this review, we discuss the current advances being made in antibody engineering and how they are being considered and used in the development of the next generation of antibodies to meet future expectations of healthcare providers, physicians and patients. Moreover, we discuss how pattern recognition receptors may provide new antibody tractable targets that may break the cycle of autoimmunity in rheumatoid arthritis.
21271796 Review of treatment response in rheumatoid arthritis: assessment of heterogeneity. 2011 Apr OBJECTIVE: Rheumatoid arthritis (RA) is a chronic, systemic, progressive, inflammatory disorder. The primary goals of treatment in RA are to reduce the signs and symptoms of disease, prevent progression of joint damage and improve patients' physical function. Patients with different sociodemographic characteristics, varying degrees of severity of illness, and comorbidities tend to exhibit differential response to treatment. The purpose of this review was to identify a broad set of factors that are associated with and/or predictive of RA treatment response and determine those that warrant further research. RESEARCH DESIGN AND METHODS: A comprehensive review of the literature from the last 10 years was performed using three key databases (PubMed, EMBASE, and Cochrane). All relevant articles that met the inclusion/exclusion criteria were selected and scored for their levels of evidence using the National Institute of Clinical Excellence (NICE) scoring method. Data on study design, interventions and treatment outcomes were abstracted using a structured abstraction table. RESULTS: A total of 30 articles were included in the review and data abstraction. Besides gender, baseline clinical variables such as C-reactive protein level, erythrocyte sedimentation rate, measures of disease activity, and Health Assessment Questionnaire scores (based on five patient-centered dimensions) were consistently associated with treatment response over time. CONCLUSIONS: This comprehensive literature review identified several factors associated with treatment response which might be valuable to include as relevant measures in future studies of RA treatment. Inclusion of these factors, particularly those in the clinical and sociodemographic domains, in the design of future trials will further the understanding that ultimately may help clinicians deliver targeted treatment to community practice RA patients, thus resulting in improved patient outcomes.
21339214 Erosions versus joint space narrowing in rheumatoid arthritis: what do we know? 2011 Mar Both erosions and joint space narrowing (JSN) are aspects of structural damage in rheumatoid arthritis. Most information is available on structural damage as one concept. However, the differential aspect of the effects on bone and cartilage could yield interesting information. Comparative information of these aspects can be based only on radiographic data on erosions and JSN. Both erosions and JSN are the consequence of inflammation, and their progression is inhibited by drugs that inhibit inflammation. These two processes often occur in parallel but joints in which erosions are present show a preference for progression of erosions and, to a lesser extent, development of JSN. The reverse is true for joints with JSN present, where there is a preference for worsening of JSN over development of erosions. Repair is possible for erosions as well as JSN and this is related to the absence of inflammation and effective treatment (especially methotrexate in combination with a tumour necrosis factor blocker).
23078261 Are persons with rheumatoid arthritis deconditioned? A review of physical activity and aer 2012 Oct 18 BACKGROUND: Although the general assumption is that patients with rheumatoid arthritis (RA) have decreased levels of physical activity, no review has addressed whether this assumption is correct. METHODS: Our objective was to systematically review the literature for physical activity levels and aerobic capacity (VO2max). in patients with (RA), compared to healthy controls and a reference population. Studies investigating physical activity, energy expenditure or aerobic capacity in patients with RA were included. Twelve studies met our inclusion criteria. RESULTS: In one study that used doubly labeled water, the gold standard measure, physical activity energy expenditure of patients with RA was significantly decreased. Five studies examined aerobic capacity. Contradictory evidence was found that patients with RA have lower VO2max than controls, but when compared to normative values, patients scored below the 10th percentile. In general, it appears that patients with RA spend more time in light and moderate activities and less in vigorous activities than controls. CONCLUSION: Patients with RA appear to have significantly decreased energy expenditure, very low aerobic capacity compared to normative values and spend less time in vigorous activities than controls.
21501785 Rheumatoid arthritis of the elbow. 2011 May Rheumatoid arthritis (RA) is the most common form of inflammatory arthropathy. RA is considered a disease of synovial joints, although it can cause various extra-articular manifestations. The synovium appears to be the primary target; however, investigations are ongoing to determine the exact etiology and pathoanatomy.
21376627 Smoking, citrullination and genetic variability in the immunopathogenesis of rheumatoid ar 2011 Apr This review describes how studies on interactions between genetic variants, and environmental factors, mainly smoking, contribute to the understanding of how autoimmunity to post-translationally (citrullinated) proteins/peptides may occur and potentially contribute to certain subsets of rheumatoid arthritis. A main message is that studies on specific immune mechanisms in a complex and heterogeneous disease like RA should be undertaken with the help of results from genetic epidemiology. By those means, it may be possible to identify subsets of RA in a way that in the end allows development and testing of precise and subset-specific interventions against environment as well as genetically defined molecular pathways, in particular those that regulate specific immune responses.
22530639 PBEF/NAMPT/visfatin: a promising drug target for treating rheumatoid arthritis? 2012 Apr NAMPT, also known as pre-B-cell colony-enhancing factor and visfatin, has been proposed to be involved in preventing apoptosis in cancer cells and, as such, has received a great deal of attention in recent years and stimulated the development to specific inhibitors for treating cancer. The role of NAMPT inhibitors as potential therapeutic agents for other diseases has not been studied extensively. Here, we describe their applicability for treating rheumatoid arthritis. We summarize current knowledge of NAMPT expression in healthy and diseased tissues, thereafter, we focus on pathological mechanisms relevant to rheumatoid arthritis that involve the NAMPT pathway and review the current status of NAMPT inhibitors being evaluated in clinical trials.
22984169 Reliability of a consensus-based ultrasound score for tenosynovitis in rheumatoid arthriti 2013 Aug OBJECTIVE: To produce consensus-based scoring systems for ultrasound (US) tenosynovitis and to assess the intraobserver and interobserver reliability of these scoring systems in rheumatoid arthritis (RA). METHODS: We undertook a Delphi process on US-defined tenosynovitis and US scoring system of tenosynovitis in RA among 35 rheumatologists, experts in musculoskeletal US (MSUS), from 16 countries. Then, we assessed the intraobserver and interobserver reliability of US in scoring tenosynovitis on B-mode and with a power Doppler (PD) technique. Ten patients with RA with symptoms in the hands or feet were recruited. Ten rheumatologists expert in MSUS blindly, independently and consecutively scored for tenosynovitis in B-mode and PD mode three wrist extensor compartments, two finger flexor tendons and two ankle tendons of each patient in two rounds in a blinded fashion. Intraobserver reliability was assessed by Cohen's κ. Interobserver reliability was assessed by Light's κ. Weighted κ coefficients with absolute weighting were computed for B-mode and PD signal. RESULTS: Four-grade semiquantitative scoring systems were agreed upon for scoring tenosynovitis in B-mode and for scoring pathological peritendinous Doppler signal within the synovial sheath. The intraobserver reliability for tenosynovitis scoring on B-mode and PD mode was good (κ value 0.72 for B-mode; κ value 0.78 for PD mode). Interobserver reliability assessment showed good κ values for PD tenosynovitis scoring (first round, 0.64; second round, 0.65) and moderate κ values for B-mode tenosynovitis scoring (first round, 0.47; second round, 0.45). CONCLUSIONS: US appears to be a reproducible tool for evaluating and monitoring tenosynovitis in RA.
22819083 Ultrasonography applications in diagnosis and management of early rheumatoid arthritis. 2012 May Ultrasonography is an elegant tool for the detection of tenosynovitis, synovitis, and erosions very early in rheumatoid arthritis, and the presence of a power Doppler signal is one of the best predictors of joint damage. Although clinical scores remain the mainstay of disease activity assessment, ultrasonography has proved to be a remarkably robust tool for reliable assessment of changes in rheumatoid arthritis. There is no evidence to suggest that problems with operator dependence would be greater than with other imaging modalities or physical examination, if performed by trained providers.
22214809 [Anti-rheumatic therapy in patients with rheumatoid arthritis undergoing hemodialysis]. 2011 Hemodialysis (HD) patients have been increasing recently. Some rheumatoid arthritis (RA) patients need hemodialysis (HD), though the proportion is not high. At present, such patients are almost treated with corticosteroids and/or nonsteroidal anti-inflammatory drugs alone, even if they have a high disease activity that would require disease-modifying anti-rheumatic drug (DMARD) therapy, partly because the safety of DMARDs in RA patients with end-stage renal disease has not been confirmed. Their joint destruction would be inevitable and lead to impaired activities of daily living. As there are no guidelines for the use of DMARDs in HD patients, here I reviewed the previous reports about the treatment of DMARDs including biologics for patients with RA undergoing HD.
21926155 Vascular function and morphology in rheumatoid arthritis: a systematic review. 2011 Nov OBJECTIVES: RA associates with significantly increased morbidity and mortality from cardiovascular disease (CVD). This may be due to complex interactions between traditional CVD risk factors, systemic rheumatoid inflammation and the vasculature. We reviewed the current literature to answer: (i) whether there is sufficient evidence that patients with RA have altered vascular function and morphology compared with normal controls; (ii) whether there is sufficient evidence to determine if such changes relate predominantly to systemic inflammation; and (iii) whether any changes of vascular function and morphology in RA can be modified with therapy. METHODS: The MEDLINE database was searched to identify publications from 1974 to 1 November 2010 pertaining to vascular function and morphology in RA. The total number of articles included in the present review was 93. This included 57 cross-sectional studies, 27 longitudinal studies without randomization and 9 longitudinal studies with randomization. RESULTS: Vascular function and morphology was impaired in RA relative to healthy controls. The majority of studies reported no associations between systemic inflammation and vascular function. Treatment with anti-inflammatory medication resulted in both transient and long-term improvements in the vasculature, but only a few studies reported associations between change in inflammation and change in vascular function and morphology. CONCLUSION: The link between systemic inflammation and vascular function and morphology is not wholly supported by the available literature. Long-term studies examining specific predictors (including CVD risk factors) on the vasculature in RA are needed.
23269876 Recent paradigm shifts in the diagnosis and treatment of rheumatoid arthritis. 2012 Dec Rheumatoid arthritis (RA) is a progressive inflammatory disease with severe symptoms of pain and stiffness. Chronic persistent inflammation of RA often leads to joint destruction, deformity and limitation of function, which ultimately results in significant deterioration of quality of life (QoL). RA is characterized pathogenetically by immunologically driven, chronic synovitis, and production of autoantibodies, such as rheumatoid factor and anti-cyclic citrullinated peptide antibodies. Although the cause of RA is yet unknown, advances in the molecular biology led to in-depth understanding of its pathogenesis, and have fostered the recent development of novel treatments. The last decade has seen the dramatic change in the landscape of RA treatment with more aggressive therapy early in the disease course and with treatment guided by a structured assessment of disease activity, with the ultimate goal of reaching remission. In addition, prevention and control of joint damage and improvement in QoL are important goals. To achieve these goals, a multidisciplinary approach to reduce disease activity with disease modifying antirheumatic drugs and biological therapy is needed. We also need to find ways to identify those patients who are at risk for more rapid disease progression who would benefit from intensive therapy early in the course of disease.
21529303 Morning symptoms in rheumatoid arthritis: a defining characteristic and marker of active d 2011 Many human biological processes are regulated by circadian rhythms, which follow 24-h cycles and involve the neuroendocrine and immune systems. Pathological manifestations of this system may also follow circadian rhythms. In rheumatoid arthritis (RA), clinical symptoms of joint stiffness, pain, and functional disability are commonly most severe in the early morning. These symptoms closely follow the circadian rhythm of the pro-inflammatory cytokine, interleukin (IL)-6. In RA, the increase in nocturnal anti-inflammatory cortisol secretion is insufficient to suppress ongoing inflammation, resulting in the morning symptoms characteristic of RA. Established diagnostic criteria for RA include morning stiffness, although it is not part of the more recent classification criteria developed to guide early treatment decisions. Measures that are widely used to monitor disease control also omit morning stiffness. However, such measures may not capture all disease activity, and one in six patients in remission or with low disease activity still experiences prolonged morning stiffness. Such findings suggest that morning symptoms in RA remain an important marker of active disease that should continue to be monitored.
21794800 [Predictors of response to biologic therapies in rheumatoid arthritis]. 2011 Mar The advent of biological therapies has revolutionized the management of rheumatoid arthritis, demonstrating effectiveness in controlling clinical and radiological damage. However, 20 to 40% of the patients will not respond to these therapies, which are associated to a very high cost. In addition, non-responder patients are exposed to possible adverse effects. For these reasons, we need to identify predictors of response to these treatments. These predictors are reviewed in this evidence-based paper and classified into genetic and non-genetic. Despite extensive search, nowadays there are no predictors powerful enough to be used in regular clinical practice. Serum factors, the presence of rheumatoid factor and anti-cyclic citrullinated peptide antibodies, are the only factors currently being used to predict the response to specific biological therapy. In the future, probably thanks to new technologies based on genomics, transcriptomics and proteomics, it will be possible to identify genetic predictors of response to biological drugs that will allow us to select suitable patients for a specific biological therapy.
22998801 Thoracic complications of rheumatoid disease. 2013 Mar Rheumatoid arthritis is a relatively common multisystem disease associated with significant mortality and morbidity. Thoracic disease, both pleural and pulmonary, is a frequent extra-articular manifestation of rheumatoid arthritis and responsible for approximately 20% of rheumatoid-associated mortality. Rheumatoid disease and its associated therapies can affect all compartments of the lung inciting a range of stereotyped pathological responses and it is not infrequent for multiple disease entities to co-exist. In some instances, development of pulmonary complications may precede typical rheumatological presentation of the disease and be the first indication of an underlying connective tissue disease. The spectrum of thoracic disease related to rheumatoid arthritis is reviewed.
23219766 Cost-effectiveness of biologic treatment for rheumatoid arthritis in clinical practice: an 2013 Jun The burden of illness of rheumatoid arthritis (RA) falls on patients, families and society through the direct costs, indirect costs, and intangible costs. A large number of RA cost-of-illness studies have been performed in recent decades with discrepant results due to patient heterogeneity, and different health-care organization, employment rate or social support, job opportunities, and methodologies used to calculate the costs. The greatest burden of RA is the indirect and the intangible costs, but how to estimate them remains controversial. The systematic use of traditional disease modifying anti rheumatic drugs has changed the evolution of the disease. However, a considerable improvement in the management of RA has been obtained since the advent of biologic response modifiers. The use of these drugs, which have demonstrated greater efficacy than conventional therapies, have tripled the direct costs of RA, which rose from about € 4000 to roughly € 12,000, in a period of five years, from 2000 to 2005. The present paper is aimed to examine the effects of this change in therapeutic strategy.
22954024 Are biological targets the final goal for rheumatoid arthritis therapy? 2012 Dec INTRODUCTION: Rheumatoid arthritis (RA) is a chronic inflammatory joint disorder that is characterized by inflammation of synovial membrane and the release of inflammatory cytokines that ultimately results in joint destruction and disability. The therapeutic treatment plan for treating RA patient initiates with disease-modifying antirheumatic agents (DMARDs) and ends with the use of biological agents. Sometimes a combination of DMARDs and the biological agents are aggressively initiated. But this is not sufficient to retard the underlying progression of the disease and hence the disease-associated pain persists. The solution lies in the treatment of causative factors. Modern therapy aims at targeting newer target sites that can not only overcome the problem of pain and disability but also minimize the occurrence of adverse effects faced by the traditional therapeutic approach. AREAS COVERED: This review covers the pathological background of the disease in brief, the traditional and newer biologicals, therapeutic targets and novel therapies for rheumatoid arthritis. EXPERT OPINION: Better management of the disease can be achieved by focusing on the causes and the factors of the disease. Newer therapies and targeting sites discussed in this review focus on treating the disability at the cellular level without affecting body's immune response and minimizing the chances of infection and inflammation.