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

ID PMID Title PublicationDate abstract
21640052 The potential roles for novel biomarkers in rheumatoid arthritis assessment. 2011 May Comprehensive management of rheumatoid arthritis (RA) requires regular monitoring of disease activity, functional status, and structural damage to facilitate optimal patient outcomes. Tight control strategies have been successfully used in other diseases including diabetes and hypertension. Tight control requires frequent disease activity measurements in order to tailor treatment for individual patients, resulting in improved patient outcomes. Current monitoring measures used in clinical practice are largely driven by subjective evaluation of signs and symptoms, which are critical but limited by assessor variability and may not reflect true biological change in a timely manner. Research suggests that novel biomarkers may provide quantitative, objective assessments of disease activity and structural damage risk in RA, which are not captured by current measures. The simultaneous use of multiple biomarkers in a single test algorithm may provide a more comprehensive quantitative representation of the overall complex heterogeneous biology of RA. This article reviews the current management strategies for monitoring RA and the potential impact that multi-biomarker assays may have on RA assessment, which may further improve clinical outcomes.
21545851 Angiogenesis in rheumatoid arthritis: a disease specific process or a common response to c 2011 Aug Angiogenesis is the formation of new blood vessels from existing vessels. During RA new blood vessels can maintain the chronic inflammatory state by transporting inflammatory cells to the site of inflammation and supplying nutrients and oxygen to the proliferating inflamed tissue. The increased endothelial surface area also creates an enormous capacity for the production of cytokines, adhesion molecules, and other inflammatory stimuli, simultaneously the propagation of new vessels in the synovial membrane allows the invasion of this tissue supporting the active infiltration of synovial membrane into cartilage and resulting in erosions and destruction of the cartilage. This angiogenic phenotype is promoted by several pro-angiogenic molecules, the most potent of which is vascular endothelial growth factor (VEGF). Although angiogenesis is recognized as a key event in the formation and maintenance the infiltration of synovial membrane during RA, it is unclear whether angiogenesis should be considered a specific feature of the disease or a common inflammation driven process. However the emergence of biological therapies, such as anti TNF blockade, has suggested that there are features of the inflammatory response that are not general but contextual to the specificity of the tissue where inflammation occurs, and point out the relevant role of tissue-resident stromal cells in determining the site at which inflammation occurs and the specific features of chronic inflammation such as that occurs in RA.
23179003 Epidermal growth factor receptor (EGFR) as a therapeutic target in rheumatoid arthritis. 2013 Mar The epidermal growth factor receptor (EGFR) has an important role in the hyperplastic growth of tumor. Similar to tumor growth, rheumatoid arthritis (RA) synovium is hyperplastic, invasive, and expresses EGFR and its ligands. Activation of EGFR signaling is responsible for synovial fibroblast proliferation in RA. Furthermore, in addition to its role in proliferation, EGFR and its ligands can induce cytokine production of synovial fibroblasts during the pathogenesis of RA. Agents that target EGFR have yielded promising results in animal experiments involving RA, pharmacologic modulations targeting EGFR, or its ligands may give rise to new therapeutic approaches for RA. In this review article, we will discuss the biological features of EGFR and summarize recent advances regarding the role of EGFR in the pathogenesis and treatment of RA.
22047152 Protein array diagnostics for guiding therapy in rheumatoid arthritis. 2011 Oct 1 Early diagnosis and effective management of rheumatoid arthritis (RA) are pivotal, given the progressive, chronic, inflammatory, multi-systemic nature of the disease. Currently, proper initiation of adequate, individually tailored interventions in RA is delayed by the difficulty of early diagnosis and the limitations of disease activity and therapeutic response assessment tools. This is a significant challenge to rheumatologists, further complicated by the dynamic and progressively evolving autoimmune nature of RA, which is characterized by several immune mediators in a complex network that regulates the perpetuation of inflammation. Protein arrays constitute the most advanced current technology that can provide a comprehensive parallel analysis of this diverse network in RA, providing an individualized insight into immune status and host immune response. The last few years have seen significant transitions in the field of protein arrays, demonstrated by a technologic shift from the bench to the bedside, paving the way for the medical and scientific community to deliver patient-specific assessments and personalized management. Screening of protein arrays with sera or tissues from patients with RA enables the probing of immune responses and the identification of autoantibody signatures that can be used for the diagnosis and therapeutic management of patients. This article reviews the technology and the applications for protein arrays in the diagnosis and prognosis of RA. Clinical assessment tools could be derived from protein arrays, which may provide a means to continually track patients, allowing better evaluation of intervention strategies on a patient-specific basis and identification of diagnostic and disease activity biomarkers that could be used to guide optimal therapy in RA.
22035431 Musculoskeletal ultrasound as a diagnostic and prognostic tool in rheumatoid arthritis. 2011 The use of musculoskeletal ultrasound (MSKUS) has increased in a variety of rheumatic conditions, particularly rheumatoid arthritis (RA). MSKUS complements the physical examination by allowing for superior visualization of synovitis and erosive changes compared to conventional radiography and provides detail comparable or supplementary to magnetic resonance imaging (MRI). This modality is also less expensive than MRI and CT scans, without claustrophobia or other contraindications, while uniquely providing dynamic, rather than static imaging. A growing body of literature for MSKUS in RA is contributing significantly to the understanding of diagnostic and prognostic utility, longitudinal assessment, and disease remission. Furthermore, scoring systems focusing on the patient level rather than individual joints have been developed, allowing for simplification of exams while still retaining accuracy and utility. The combination of these advances has led to increased use of MSKUS in RA in the realm of research as well as at the bedside and in the clinic.
21861862 Positive regulators of osteoclastogenesis and bone resorption in rheumatoid arthritis. 2011 Jul 28 Bone destruction is a frequent and clinically serious event in patients with rheumatoid arthritis (RA). Local joint destruction can cause joint instability and often necessitates reconstructive or replacement surgery. Moreover, inflammation-induced systemic bone loss is associated with an increased fracture risk. Bone resorption is a well-controlled process that is dependent on the differentiation of monocytes to bone-resorbing osteoclasts. Infiltrating as well as resident synovial cells, such as T cells, monocytes and synovial fibroblasts, have been identified as sources of osteoclast differentiation signals in RA patients. Pro-inflammatory cytokines are amongst the most important mechanisms driving this process. In particular, macrophage colony-stimulating factor, RANKL, TNF, IL-1 and IL-17 may play dominant roles in the pathogenesis of arthritis-associated bone loss. These cytokines activate different intracellular pathways to initiate osteoclast differentiation. Thus, over the past years several promising targets for the treatment of arthritic bone destruction have been defined.
22819085 Disease activity assessment and patient-reported outcomes in patients with early rheumatoi 2012 May Quantitative assessment of disease activity and patient-reported outcomes are recognized as valuable in the management of rheumatoid arthritis (RA). Complexities of assessment of RA include challenges concerning measures themselves, as a gold standard measure for disease status does not exist. This article discusses the hurdles in the implementation of quantitative assessment of RA in usual clinical care and also provides an example to monitor patients with early RA.
22085514 [Employee participation by patients with rheumatoid arthritis and spondylarthritis. Biolog 2011 Rheumatoid arthritis (RA) and the various types of spondylarthritis (SpA) contribute significantly to employee disability. Each of these inflammatory diseases has a great impact on physical and mental health, thereby restricting one's ability to participate in one's social roles. This may result in decreased productivity during working hours (sickness presenteeism), absenteeism and eventually, disablement, with financial consequences for the patient as well as society. By incorporating biologicals into treatment strategies, the health of patients with RA and SpA can be better regulated; however, the cost of such treatment has risen considerably. There are indications that part of these high treatment expenditures can be regained by improved employee productivity of these patients.
22174195 The need to better classify and diagnose early and very early rheumatoid arthritis. 2012 Feb Early rheumatoid arthritis (RA) and very early RA are major targets of research and clinical practice. Remission has become a realistic goal in the management of RA, particularly in early disease. The 2010 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) RA classification criteria, the EULAR treatment recommendations for RA, and the EULAR recommendations for the management of early arthritis focus on early disease and translate the knowledge related to early RA into classification and management. Nevertheless, there is a need for further improvement and progress. Results from 6 recent studies are summarized, evaluating the performance of the 2010 ACR/EULAR RA classification criteria. The data show a significant risk of misclassification, and highlight that overdiagnosis and underdiagnosis may become important issues if the criteria recommend synthetic and biological disease-modifying antirheumatic drugs. Therefore, some considerations are presented on how the current problems and limitations could be overcome in clinical practice and future research. A consensus is needed to better define the early phase of RA and differentiate from other early arthritis. The possible effect of misclassification on spontaneous and drug-induced remission of early and very early RA awaits further elucidation. Such research will eventually lead to more reliable diagnostic and classification criteria for new-onset RA.
21392764 The effectiveness of nurse-led care in people with rheumatoid arthritis: a systematic revi 2011 May OBJECTIVES: The objective of this systematic review was to determine the effectiveness of nurse-led care in rheumatoid arthritis. DESIGN: Systematic review of effectiveness. DATA SOURCES: Electronic databases (AMED, CENTRAL, CINAHL, EMBASE, HMIC, HTA, MEDLINE, NHEED, Ovid Nursing and PsycINFO) were searched from 1988 to January 2010 with no language restrictions. Inclusion criteria were: randomised controlled trials, nurse-led care being part of the intervention and including patients with RA. REVIEW METHODS: Data were extracted by one reviewer and checked by a second reviewer. Quality assessment was conducted independently by two reviewers using the Cochrane Collaboration's Risk of Bias Tool. For each outcome measure, the effect size was assessed using risk ratio or ratio of means (RoM) with corresponding 95% confidence intervals (CI) as appropriate. Where possible, data from similar outcomes were pooled in a meta-analysis. RESULTS: Seven records representing 4 RCTs with an overall low risk of bias (good quality) were included in the review. They included 431 patients and the interventions (nurse-led care vs usual care) lasted for 1-2years. Most effect sizes of disease activity measures were inconclusive (DAS28 RoM=0.96, 95%CI [0.90-1.02], P=0.16; plasma viscosity RoM=1 95%CI [0.8-1.26], p=0.99) except the Ritchie Articular Index (RoM=0.89, 95%CI [0.84-0.95], P<0.001) which favoured nurse-led care. Results from some secondary outcomes (functional status, stiffness and coping with arthritis) were also inconclusive. Other outcomes (satisfaction and pain) displayed mixed results when assessed using different tools making them also inconclusive. Significant effects of nurse-led care were seen in quality of life (RAQoL RoM=0.83, 95%CI [0.75-0.92], P<0.001), patient knowledge (PKQ RoM=4.39, 95%CI [3.35-5.72], P<0.001) and fatigue (median difference=-330, P=0.02). CONCLUSIONS: The estimates of the primary outcome and most secondary outcomes showed no significant difference between nurse-led care and the usual care. While few outcomes favoured nurse-led care, there is insufficient evidence to conclude whether this is the case. More good quality RCTs of nurse-led care effectiveness in rheumatoid arthritis are required.
21743087 Cardiovascular education for people with rheumatoid arthritis: what can existing patient e 2011 Oct Patient education is an integral component of the management of chronic diseases. Education programmes designed for people with RA have historically aimed to improve their arthritis symptoms and outcomes. Novel educational material is required to address significant comorbidities, particularly cardiovascular disease (CVD) associated with RA. We appraise the components of education programmes incorporated in disease management in people with RA and programmes used for CVD prevention in the general population, including their design and delivery, use of behaviour theory, evaluation and long-term efficacy. We then integrate the findings in order to inform the development of educational material specifically addressing CVD in RA. This approach may be useful for other major comorbidities of RA as well as other musculoskeletal conditions.
21645962 Emerging role of ultrasonography in rheumatoid arthritis: optimizing diagnosis, measuring 2011 Aug Ultrasonography is a sensitive imaging modality that provides valuable information regarding early inflammatory changes that are not detected by clinical examination or X-rays, such as subclinical synovitis and erosions. This information may improve the management of rheumatoid arthritis by providing a more timely and accurate diagnosis, identifying poor prognostic factors, more accurately monitoring response to therapeutic intervention, improving treatment decisions and more accurately assessing remission. Ultrasonography could play a critical role in minimizing disease activity through strict monitoring and aggressive therapeutic adjustment, which has emerged as an approach to improve long-term outcomes for patients with rheumatoid arthritis.
22584928 Rheumatoid arthritis: role of the nurse and multidisciplinary team. 2012 Mar 22 Rheumatoid arthritis is a complex chronic inflammatory condition which has both musculoskeletal and extra-articular effects. It is the most common inflammatory arthropathy, and has the potential to cause a significant impact on quality of life. The predominant features of the disease are inflammation, pain, reduced levels of function and increased morbidity. Despite the number of treatments available to suppress the effects of rheumatoid arthritis, it is not always possible to establish good control of the disease. It is imperative that the multidisciplinary team are involved with care to ensure that independence is maintained and function optimized. The role of the nurse in the management of rheumatoid arthritis is varied, ranging from providing specialist advice about how to manage the condition to caring for patients who are having joint replacements as a result of the increased levels of pain and damage it can cause.
22422498 Apoptosis as a mechanism of action of tumor necrosis factor antagonists in rheumatoid arth 2012 Apr Tumor necrosis factor (TNF) antagonists are drugs developed to block endogenous TNF, an essential proinflammatory molecule with a central role in the pathogenesis of rheumatoid arthritis (RA). Although extensive studies have been performed concerning the mode of action of TNF-blocking agents, there are still many unresolved questions and potential differences between different TNF-blocking drugs. One unresolved issue is to what extent apoptosis is affected by TNF blockade in RA. We provide an overview of studies that have investigated the proapoptotic effect of different anti-TNF drugs in RA, searching for a unified interpretation of somewhat contradictory data.
22530637 Sphingosine kinase and sphingosine-1-phosphate receptors: novel therapeutic targets of rhe 2012 Apr Rheumatoid arthritis (RA) is a chronic, destructive, autoimmune joint disease characterized by elevated levels of proinflammatory cytokine production. Sphingosine kinase (SphK) phosphorylates sphingosine into sphingosine-1-phosphate. Synovial fluid of RA patients exhibits significantly higher levels of S1P than their non-inflammatory osteoarthritis counterparts. SphK blockade suppresses cytokines and MMP-9 release in RA peripheral blood mononuclear cells. In addition, downregulation of SphK1 either through a specific siRNA approach or transgenic human TNF-α SphK1-deficient mice (hTNF-α/SphK1(-/-)) exhibit significantly less synovial inflammation and joint pathology. By contrast, SphK2 modulation leads to disease exacerbation. These results clearly demonstrate that such anti- and proinflammatory potential of SphK1/2 modulation may alter the outcome in RA synovitis and raises the possibility that drugs that specifically target SphK1 activity may play a beneficial role in the treatment of RA and other autoimmune rheumatic diseases.
20964640 The influence of early life factors on the risk of developing rheumatoid arthritis. 2011 Jan Rheumatoid arthritis (RA) is a chronic inflammatory disease that develops as a result of the interaction between genetic and environmental risk factors. Although increasing evidence shows the importance of genes in determining the risk of RA, it is clear that environmental factors also have a vital role. Studies to date have tended to concentrate on environmental influences around the time of disease onset. However, a number of pieces of evidence, including the fact that autoantibodies, such as rheumatoid factor (RF), can develop several years before the onset of clinical disease, suggest that environmental factors may influence disease susceptibility during early life. Several recent studies lend weight to this possibility, with an increased risk of RA in the offspring of mothers who smoked during pregnancy and in those with higher birth weight. There has also been a suggestion that the risk of RA is reduced in breast-fed infants. We describe the evidence surrounding the effect of early life factors on the risk of developing RA and possible mechanisms by which they may act.
21960179 Role of osteoclasts and interleukin-17 in the pathogenesis of rheumatoid arthritis: crucia 2012 Mar Many papers have reported that osteoclasts play an important role in the pathogenesis of rheumatoid arthritis (RA); however, when we started to investigate the pathogenesis of RA, the roles of osteoclasts were not highlighted in RA bone resorption. In recent years, the number of articles on the roles of osteoclasts and interleukin (IL)-17 in the pathogenesis of RA has increased exponentially. In this review article, we describe our articles on the roles of osteoclasts and IL-17 in joint destruction in RA, from 1990 to 2011, and highlight a novel term, 'human osteoclastology', which we have used since 2008.
22137917 Precipitating and perpetuating factors of rheumatoid arthritis immunopathology: linking th 2011 Aug Rheumatoid arthritis (RA) is considered to occur when genetic and environmental factors interact to trigger immunopathological changes and consequently an inflammatory arthritis. Over the last few decades, epidemiological and genetic studies have identified a large number of risk factors for RA development, the most prominent of which comprise cigarette smoking and the shared epitope alleles. These risks appear to differ substantially between anti-cyclic citrullinated peptide (ACPA)-positive and ACPA-negative disease. In this article, we will summarise the risk factors for RA development that have currently been identified, outlining the specific gene-environment and gene-gene interactions that may occur to precipitate and perpetuate autoimmunity and RA. We will also focus on how this knowledge of risk factors for RA may be implemented in the future to identify individuals at a high risk of disease development in whom preventative strategies may be undertaken.
22018195 Low-dose corticosteroids and disease modifying drugs in patients with rheumatoid arthritis 2011 Sep Low-dose glucocorticoids (GCs) exhibit a differential effect on continuation of disease-modifying anti-rheumatic drugs (DMARDs), and the degree of adverse effects (AE) associated with DMARDs. Therefore, GCs address important problems in DMARD use in rheumatoid arthritis (RA), i.e. cumulative toxicity and frequent AE. Low-dose GCs often are recommended to achieve a better symptomatic control or as 'bridge therapy' before the onset of action of DMARDs. RA patients with GC co-medication had better radiographic outcomes but experienced more GC-related AE. Further long-term studies are needed to focus on timing of administration, duration and identification of risk factors for developing AE to establish the optimal use of GCs in the treatment of RA.
21870424 Ethno biological usage of zoo products in rheumatoid arthritis. 2011 Aug Rheumatoid arthritis (RA) is one of the most common autoimmune disorder which causes swelling, redness, pain, stiffness, restriction of limb movements, decreases life expectancy and early death of the patients. Available drugs include non steroidal anti-inflammatory and analgesics, disease modifying anti-rheumatic drugs and steroids (glucocorticoids etc). All these drugs have their own limitations such as gastrointestinal irritations, cardiovascular problems, and drug dependency. Search for alternative therapy from natural products are being ventured throughout the world. Zoo therapy in arthritis, a common practice of the ancient times that have been mentioned in traditional and folk medicine. The scientific basis of some of the zoo products are being explored and have been showing promising results in experimental rheumatoid arthritis. These therapies have minimum side effects and many of them have potential to give rise to drug development clues against rheumatoid arthritis. The present review is an effort to establish the folk and traditional treatment of rheumatoid arthritis using zoo products.