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ID PMID Title PublicationDate abstract
16258413 [Defect of glycosylation of immunoglobulin G in rheumatoid arthritis patients]. 2005 Rheumatoid arthritis (RA) is a multisystem disorder in which immunological abnormalities result in symmetrical joint inflammation, articular erosion, and extra-articular involvement. The etiology of RA is still unknown, but a defect in the glycosylation of IgG may be involved in its immunopathogenesis. Several studies have shown a correlation between the amount of IgG lacking galactose and the activity of RA. IgG galactosylation has been shown to be a useful marker of early RA and an indicator of poor prognosis. Analysis of IgG galactosylation may offer an insight into disease pathogenesis and may also be useful in RA diagnosis.
16932639 Mechanisms of disease: the molecular and cellular basis of joint destruction in rheumatoid 2005 Dec Rheumatoid arthritis is a complex systemic disease that ultimately leads to the progressive destruction of articular and periarticular structures. Novel data indicate that the innate immune system (through activation of Toll-like receptors) is involved in articular pathophysiology, including the recruitment of inflammatory cells, and that periarticular factors such as adipocytokines contribute to the perpetuation of joint inflammation. The deleterious process of joint destruction is mediated by intracellular signaling pathways involving transcription factors, such as nuclear factor kappaB, cytokines, chemokines, growth factors, cellular ligands, and adhesion molecules. Advances in molecular biology techniques have identified T-cell-independent and B-cell-independent pathways that operate at different stages of the disease. Cytokine-independent pathways appear to be responsible for maintaining basic disease activity that is not affected by currently available therapies. Using this knowledge in combination with gene-transfer and gene-silencing approaches, bench-to-bedside strategies will be developed, thus enabling the creation of novel treatments for rheumatoid arthritis.
16081030 Additional diagnostic and clinical value of anti-cyclic citrullinated peptide antibodies c 2005 Jul In the past decade significant advantages have been made in the treatment of rheumatoid arthritis (RA) and therapeutic strategies have changed a lot. These days, highly effective disease modifying anti-rheumatic drugs enable intervention early in the disease process, in order to prevent major joint damage. For years, serological support in the diagnosis of RA has been limited to the presence of rheumatoid factors, although not very specific for RA. During the last years a variety of circulating non-RF antibodies have been discovered and reported to be of potential diagnostic value. CCP2 proved to be a very disease-specific and even sensitive marker for RA. In addition to the diagnostic properties, CCP showed to be a good prognostic marker, CCP helps to predict the erosive or nonerosive progression of the disease, and CCP is already present early in the disease. This diagnostic tool enables the clinician to choose the optimal therapeutic management for each single RA patient.
16259334 [Modern treatment of rheumatoid arthritis]. 2005 Oct 2 Modern treatment of rheumatoid arthritis. Rheumatoid arthritis is a chronic inflammatory disease of unknown etiology, which is characterised by pain, loss of capability to work, in severe cases the life expectancy is also reduced. The disease cannot be cured with current therapeutic possibilities, but complaints can be reduced, the destruction can be retarded. The treatment is more efficient in the early stage of the disease, but early diagnosis is difficult because of insidious onset and limited sensitivity of diagnostic methods. The complaints can be alleviated by nonsteroidal anti-inflammatory drugs and transient glucocorticoid treatment, but risk of continuous glucocorticoid therapy is significant. To prevent structural damage disease modifying antirheumatic drugs are used. Out of these methotrexate is the most effective and it is well tolerated. Destruction of the joints is the consequence of inflammation, so intensity of drug treatment must be adjusted to inflammatory activity. For monitoring in clinical practice the composite index disease activity score is recommended. To achieve the reduction of inflammatory activity the dosage of disease modifying drugs can be increased, they can be switched or combined, and continuous glucocorticoid treatment can be started. In cases refractory to conventional treatment it is possible to inhibit the activity of proinflammatory cytokines, which play a pivotal role in pathomechanism of rheumatoid arthritis. In synovitis limited to one joint intraarticular glucocorticoid injection can be given, in refractory cases synovectomy is indicated. Destruction of the joints can be partially corrected by exercise, orthoses and after all with surgery.
15723198 A review of the action of tacrolimus (FK506) on experimental models of rheumatoid arthriti 2005 Jan Tacrolimus (FK506) is an immunosuppressive drug, widely used for organ transplantation and atopic dermatitis. Tacrolimus exerts its immunosuppressive effects primarily by interfering with the activation of T cells, via inhibition of calcineurin. Recent clinical studies have also demonstrated the efficacy of tacrolimus in the treatment of rheumatoid arthritis (RA), an autoimmune disease in which T cells play a pivotal role in pathogenesis. Inflammatory cytokines such as TNF-alpha, IL-1 beta, and IL-6 are involved in development of the disease. Recently, modes of action of tacrolimus on RA have been intensively studied in in vitro and animal arthritis models, demonstrating that tacrolimus exerts various novel actions as an anti-rheumatic drug. The pharmacological action of tacrolimus suggests that it has potential to specifically suppress the production of pathogenic inflammatory cytokines with a low frequency of infection, improve joint inflammation and bone/cartilage destruction, fully recover loss of functional status, exert rapid relief in arthritic pain, and promote osteogenic and chondrogenic differentiation. Here we review the action of tacrolimus on experimental models of RA, with a focus on our recent studies, and provide further insight into experimental models used for identifying efficacious anti-rheumatic drugs.
17065191 Therapeutic status of radiosynoviorthesis of the knee with yttrium [90Y] colloid in rheuma 2007 Jan Radiosynoviorthesis (RSO) with an yttrium-90 colloid offers a local and minimally invasive therapy for treating inflammatory hypertrophy of the synovial membrane of the knee that has arisen from numerous kinds of disorder: these include rheumatoid arthritis (RA), osteoarthritis (OA), spondyloarthropathy, villonodular synovitis and others. There is substantial evidence that this treatment is efficacious and that, in view of the benefits that it offers, its tolerability and safety are very good. Administration should be restricted to patients in whom other therapies (including locally injected corticoids) have failed, and proper attention must be paid to correct administration, including post-treatment immobilization and the co-administration of corticoids, to minimize the risk of leakage and of efflux through the puncture channel.
15720275 The role of synovial fibroblasts in mediating joint destruction in rheumatoid arthritis. 2005 Rheumatoid arthritis (RA) is a chronic, inflammatory joint disease with systemic involvement that affects about 1% of the Western population. The progressive destruction of affected joints is a major characteristic of the disease and distinguishes RA from other acute and chronic arthritides. The etiology of RA is unknown, and a variety of genetic and environmental factors are being discussed as potential causes of the disease. However, in contrast to our incomplete understanding of the etiology, the knowledge about molecular mechanisms leading to joint destruction has advanced considerably over the past years. Thus, a large number of studies have investigated the presence and interplay of several types of cells in rheumatoid synovium, such as lymphocytes, macrophages and fibroblasts. They have led to the understanding that cells in the rheumatoid synovium form a network, which interacts through direct cell-to cell contacts as well as the release of a multitude of cytokines. The use of novel molecular techniques together with the development of new animal models has revised our concept on the pathogenesis of RA and specifically on the role of fibroblasts in initiation and progression of joint destruction. This article will review current data and hypotheses on disease mechanisms by which fibroblasts are involved in the destruction of joints in RA.
17023257 Systemic rheumatoid vasculitis: a review. 2006 Oct OBJECTIVES: To review the most recent information on the incidence, clinical course, pathology, pathogenesis, diagnosis, and treatment of rheumatoid vasculitis (RV), including the still scanty data on the use of biologics. METHODS: PubMed and MEDLINE databases (1950-2006) were searched for the key words "vasculitis" and "rheumatoid arthritis"; and "rheumatoid arthritis" and "extra-articular manifestations." All relevant articles in English and French were reviewed. Additional words used in follow-up research include "anti-TNF," "rituximab," "IL-1 receptor antagonists," and "CTLA-4 Ig," all in conjunction with "vasculitis." Pertinent secondary references were also retrieved. RESULTS: RV is an inflammatory condition of the small- and medium-sized vessels that affects a subset of patients with established rheumatoid arthritis (RA) (approximately 1 to approximately 5%). It has a vast array of clinical manifestations with a predilection for the skin (peripheral gangrene, deep cutaneous ulcers) and the peripheral nervous system (mononeuritis multiplex). Because of the lack of specific signs and symptoms, the diagnosis relies on the exclusion of other causes of similar lesions (diabetes, atherosclerosis, drug reactions, infection, neoplasias) and, ideally, on the histopathological demonstration of necrotizing vasculitis. Despite the availability of a host of promising new drugs for the treatment of RA, no clinical trials have tested their efficacy in RV; therefore, its management remains largely empirical. CONCLUSIONS: Although RV has apparently been decreasing over the last 2 decades, possibly as a consequence of the more energetic approach to the management of RA currently used, it remains an important complication of RA that needs to be promptly recognized and treated.
16932675 Technology insight: gene transfer and the design of novel treatments for rheumatoid arthri 2006 Mar Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by systemic inflammation and joint destruction. Novel therapies have emerged during the past decade, marking a new era in the treatment of RA. Meanwhile, in vivo and in vitro gene-transfer studies have provided valuable insights into mechanisms of disease pathogenesis. Advanced gene-delivery techniques and animal models promise further progress in RA research and the development of novel therapeutic strategies for this disease. In this article we provide an overview of the wide spectrum of potential targets that have been identified so far, discuss currently available gene-transfer methods, and outline the barriers that need to be overcome for these approaches to be successfully applied in daily practice.
16530013 A gut feeling for joint inflammation - using coeliac disease to understand rheumatoid arth 2006 Apr Major advances have been made in the molecular understanding of coeliac disease, initiated by the identification of intestinal gluten-reactive T cells. It is now clear that this common intestinal disorder, which is precipitated by the ingestion of wheat gluten, is mediated by DQ2-restricted T cells specific for gluten peptides modified by transglutaminase 2, the same enzyme that is targeted by disease-specific autoantibodies. Interestingly, many of the important features identified in coeliac disease, including HLA association, target organ T-cell infiltration, disease-specific autoantibodies and the distinct targeting of in vivo modified antigens, are also present in rheumatoid arthritis. The experiences from coeliac disease should therefore help identify disease-relevant T-cell epitopes in rheumatoid arthritis.
16633925 Potential impact of observational cohort studies in Japan on rheumatoid arthritis research 2006 For better management of rheumatoid arthritis (RA) patients, we need information both from well-designed clinical trials, such as randomized controlled trials, and from observational cohorts. Observational cohort study has not been developed in Japanese RA patients; however, two cohorts, IORRA (formerly J-ARAMIS) from 2000 and NinJa by iR-net from 2002, have been established. These two cohorts are an important source not only for better management of Japanese RA patients but also for solutions to a variety of issues concerning RA clinical practice in general. In this minireview, necessities of observational cohort studies are discussed.
16331788 The evidence for magnetic resonance imaging as an outcome measure in proof-of-concept rheu 2005 Dec Magnetic resonance imaging (MRI) has now been used extensively in cross-sectional and observational studies as well as in controlled clinical trials to assess disease activity and joint damage in rheumatoid arthritis (RA). MRI measurements or scores for erosions, bone edema, and synovitis have been developed and validated by several groups. The OMERACT criteria require that outcome measures demonstrate adequate validity, discriminative power, and feasibility if they are to be useful in clinical trials. Specific performance targets for these criteria depend on the scientific, regulatory, logistical, and financial context of the study in question. We review the extent to which MRI assessments of joint erosion, bone edema, and synovitis fulfil these criteria, particularly as they relate to proof-of-concept RA clinical trials.
15660460 Analyzing synovial tissue samples. What can we learn about early rheumatoid arthritis, the 2005 Jan The synovium is the key target of the disease process in rheumatoid arthritis (RA). Examination of synovial tissue samples may provide insight into the events that take place in different phases of the disease and may help to decipher the mechanism of action of antirheumatic treatment. This review describes the features of synovitis in early RA, which clearly represent chronic inflammation. There is marked interindividual variability, suggesting that RA consists of different pathogenetic subsets. Evaluation of serial synovial tissue samples has shown that effective treatment is associated with a reduction in synovial macrophages, independent of the specific mechanism of action of the compound. This suggests that these are key effector cells in the pathogenesis. In addition, it provides a biomarker that can be used in clinical trials.
16396713 From clinical trials to the bedside: how can we treat patients with rheumatoid arthritis a 2005 Nov In the last few years management of rheumatoid arthritis (RA) has changed substantially due to the availability of new drugs and newer therapeutical strategies. Controlled randomised clinical trials (RCT) have allowed us to analyse the efficacy and safety of all these innovative approaches. Unfortunately, these RCTs are not free from criticisms and their rigid inclusion and exclusion criteria may increase the differences between the ideal patients enrolled and the majority of patients seen in standard clinical care. This review focuses on actual clinical practice, with particular attention on patient comorbidities and all the conditions which have been designated as exclusion criteria in the most important registration RCTs. We will attempt to provide an overview of the most widely used strategies in RA therapy.
16277701 Dipeptidyl peptidase IV activity and/or structure homologs: contributing factors in the pa 2005 Several of the proinflammatory peptides involved in rheumatoid arthritis pathogenesis, including peptides induced downstream of tumor necrosis factor-alpha as well as the monocyte/T cell-attracting chemokines RANTES and stromal cell-derived factor (SDF)-1alpha and the neuropeptides vasoactive intestinal peptide (VIP) and substance P, have their biological half-lives controlled by dipeptidyl peptidase IV (DPPIV). Proteolysis by DPPIV regulates not only the half-life but also receptor preference and downstream signaling. In this article, we examine the role of DPPIV homologs, including CD26, the canonical DPPIV, and their substrates in the pathogenesis of rheumatoid arthritis. The differing specific activities of the DPPIV family members and their differential inhibitor response provide new insights into therapeutic design.
16278497 Clinical data gap between phase III clinical trials (pre-marketing) and phase IV (post-mar 2005 Fall BACKGROUND: There are fundamental differences in design between phase III clinical trials and phase IV post-marketing studies that involve patient characteristics, the clinical setting (environment) and the manner of drug use. As well, many phase IV studies are extensions of randomized clinical trials (RCTs) and suffer from selection bias. OBJECTIVE: To determine if the data obtained from RCTs of etanercept (Enbrel) in the treatment of rheumatoid arthritis would be representative of the effects attainable in community practice. METHOD: An analysis was conducted comparing data from published RCTs of etanercept use in rheumatoid arthritis patients with data collected in a community based cohort study that was not an extension of an RCT. RESULTS: Baseline clinical data, such as tender or painful joint count, patient's global assessment, the heath assessment questionnaire, physical and mental component summary of the SF-36, and rheumatoid arthritis drug profile were significantly different between the patients receiving etanercept in the phase IV community cohort study and the patients enrolled in the RCTs. Differences in the baseline data for the control patients were also noted amongst the RCT studies. The treatment outcome, American College of Rheumatology (ACR) response rate of 20%, 50% and 70% at 6 month, was the same between the cohort study and the RCTs, but at 12 months the clinical response was less for the community based patients than for the RCT patients. At 6 months there were fewer withdrawals involving community-based patients than RCT patients due to less frequent withdrawals associated with lack of efficacy. At 12 months the withdrawal rate due to either a lack of efficacy or from adverse events was similar between data sets. CONCLUSION: The data from the etanercept phase III RCTs may not reflect the characteristics of patients using etanercept in community practice, nor the clinical outcomes observed by RA patients at 12 months. These discrepancies may be derived from methodological differences in study design and patient selection. On the other hand, outcomes such as withdrawal rates at 12 months appear comparable between the two types of populations.
16394639 [The pathogenic role and production system of autoantibody in rheumatoid arthritis]. 2005 Dec Rheumatoid arthritis (RA) is an autoimmune disease that affects 1% of the population worldwide, however the pathogenic role remains elusive. Successful treatment with anti-CD20 therapy highlighted the importance of B cells in RA. Several antibodies (Abs) were identified from sera from RA patients such as rheumatoid factor, anti-CCP Abs, anti-glucose-6-phosphate isomerase Abs, anti-calpastatin Abs, anti-soluble gp130 Abs, anti-collagen type II Abs, etc. In this review, we will focus on the pathogenicity and production system of auto-Abs in RA, and also explain about recent advance from human study.
16265712 Incorporating the patient perspective into outcome assessment in rheumatoid arthritis--pro 2005 Nov The Patient Perspective Workshop at OMERACT 7 addressed the question of assessing the outcomes of intervention in rheumatoid arthritis (RA) from the perspective of those who experience the disease. A particular emphasis at this workshop was placed on fatigue, but other areas included well-being, real-time assessment, patient priorities, and needs in early and late disease. Through a series of overview presentations, discussion groups, and plenary sessions, workshop participants (who included 19 patients) clarified what is known and what are the outstanding issues for future research. The importance of further work on clarifying the validity of fatigue measurements in RA has been confirmed, and with at least one suitable instrument available there will be strong pressure to include fatigue in a redefined core set of outcome measures in RA. In the other 4 areas covered there are important issues that can be addressed by enquiry and experiment and that together provide a challenging research agenda. At the final plenary session the OMERACT conference endorsed, by a large majority, the proposal that fatigue may warrant consideration for inclusion in the OMERACT core set for RA.
16960246 Rheumatoid arthritis: a primer for pharmacists. 2006 Sep 15 PURPOSE: The epidemiology of rheumatoid arthritis (RA), its pathophysiology and immune mechanisms, and its clinical manifestations are reviewed. The signs, symptoms, and radiographic and biochemical changes noted in mild, moderate, and severe disease are discussed and the systemic nature of RA and its adverse impact on survival are addressed. Traditional and newer scoring instruments to measure disease severity, progression, disability, and response to therapy are reviewed and introduced, respectively. The impact of RA on disability and quality of life (QOL) is also explored. SUMMARY: RA, a chronic inflammatory autoimmune disease that involves the synovial membrane and extraarticular sites, affects approximately 1-2% of the population, with women 2-3 times as likely to be affected as men. If RA is not treated aggressively, its clinical course is characterized by progressive physical disability and reduced QOL. CONCLUSION: Increased knowledge of the cellular and immune mechanisms involved in RA has identified new drug targets.
15660465 Arthritis in Canada: what do we know and what should we know? 2005 Jan Doctors' visits for inflammatory arthritis reportedly represent only 6% of the overall visit rates for all arthritis and related conditions (163 per 1000), with about 40% of these patients seeing a specialist. Data from provincial drug plan databases show that although the proportion of the population aged 65 years and older with prescriptions for disease modifying antirheumatic drugs increased to 1% in 2000, this is only half the expected prevalence of rheumatoid arthritis in this age group. There are large provincial variations. Despite data on the efficacy and importance of treatment of early inflammatory arthritis, research is lacking on: the experience of arthritis, decision-making about seeking medical care, and factors affecting access to, and payment for, treatment, including drugs and rehabilitation; primary care decision-making about referral and treatment; organizational aspects of specialist care and access to drugs; and new ways of delivering services to reach patients in underserviced or remote areas. Monitoring the population impact of arthritis, including economic costs, is a priority for research, as are epidemiological studies on risk factors.