Browse

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

ID PMID Title PublicationDate abstract
18086905 Arthroscopic synovectomy in rheumatoid arthritis of wrist. 2007 Dec The wrist is the most commonly involved region of the upper extremity in rheumatoid arthritis (RA). Because the wrist joint becomes involved early during the disease course and its involvement rapidly progresses, and because the disabilities associated with progressive RA are significant, early and adequate treatment must be introduced to prevent disease progression. Various treatment methods can be employed to treat RA wrists based on radiological and clinical findings. Arthroscopic synovectomy is recommended for pain relief and functional recovery in early stage RA, and is also helpful in advanced staged RA with Larsen stage III. However, arthroscopic synovectomy is not recommended as an effective method of treatment for all patients with advanced radiographic changes. Nevertheless, arthroscopic synovectomy may delay the need for complex surgery, such as wrist arthrodesis or total wrist arthroplasty in selective cases. Although arthroscopic synovectomy of the wrist cannot improve grip strength or range of motion, it can reduce wrist pain and improve function, and thus facilitate return to work.
16602022 [Planning of orthopedic surgery for rheumatoid arthritis]. 2006 May The inflammatory process in rheumatoid arthritis is progressive and ends in destruction of the cartilage. Subsequent instability and mutilation of the joint might happen. The classification of destruction can be done by X-rays and assessment of the clinical picture. Depending on the radiologic stage different therapy concepts, ranging from conservative to operative, are established. It is the aim of surgery to restore motion and function in a painless joint. Surgery can be done to prevent the joint from further destruction or to replace the joint after resection. Different concepts based on radiologic findings are presented in this review.
18384257 An update on methotrexate pharmacogenetics in rheumatoid arthritis. 2008 Apr Rheumatoid arthritis (RA) is a systemic inflammatory disorder that mainly affects the joints. When left untreated, the disease can result in irreversible joint damage with high morbidity and mortality. Disease-modifying antirheumatic drugs are the cornerstones of treatment in RA. Disease-modifying antirheumatic drugs not only ameliorate the clinical signs and symptoms of disease, but also prevent the radiographic progression of joint damage. Methotrexate is one such disease-modifying antirheumatic drug that has been used in the treatment of RA for over two decades with excellent long-term efficacy and safety. However, there is significant variability in patients' response to methotrexate, both in terms of efficacy and toxicity. At the present time, there are no reliable means of predicting, a priori, an individual patient's response to methotrexate. In this review, recent published literature on the pharmacogenetics of methotrexate in RA is highlighted. Pharmacogenetics may be a powerful tool for optimizing methotrexate therapy in patients with RA.
18157559 The burden of rheumatoid arthritis and access to treatment: outcome and cost-utility of tr 2008 Jan Within the series of articles investigating the burden of rheumatoid arthritis (RA), this paper reviews the methods used for economic assessment of the RA treatments by HTA agencies and other bodies involved in cost-effectiveness analysis and the current status of the field. The overall methods, as well as the challenges, of cost-effectiveness analysis in RA are common to all chronic progressive diseases where much of the treatment benefit is delayed, while costs occur immediately. Also, as in all disabling diseases, much of the costs occur outside the health-care system, due to the rapid loss of work capacity and the need for informal care in the later stages of the disease. Thus, it is essential to adopt a long-term view and consider costs from the perspective of society, rather than the health-care service, to increase the relevance of the results for policy making.
16757672 Proteomics: applications to the study of rheumatoid arthritis and osteoarthritis. 2006 Jun The study of both DNA and protein technologies has been marked by unprecedented achievement over the last decade. The completion of the Human Genome Project in 2003 is representative of a new era in genomics; likewise, proteomics research, which has revolutionized the way we study disease, offers the potential to unlock many of the pathophysiologic mechanisms underlying the clinical problems encountered by orthopaedic surgeons. These new fields are extending our approach to and investigation of the etiology and progression of musculoskeletal disorders, notably rheumatoid arthritis and osteoarthritis. Advances in proteomics technology may lead to the development of biomarkers for both rheumatoid arthritis and osteoarthritis. Such biomarkers would improve early detection of these diseases, measure response to treatment, and expand knowledge of disease pathogenesis.
18336247 Gene therapy for rheumatoid arthritis: recent advances. 2008 Feb The treatment of rheumatoid arthritis (RA) in the last decade has made enormous advances with the use of biological therapies. However, these therapies have serious limitations such as the expense, side-effects, and the requirement for repeated injections, each of which can potentially be obviated by gene therapy. A gene therapy approach for the treatment of RA has the potential to stably deliver a gene product or multiple products in a target-specific, disease-inducible manner. There are many studies investigating gene therapy in RA, the majority of which have been designed to test proof-of-principle in an animal model. With an abundance of animal studies that have established much promise, the field is now at the early stage of moving towards human trials, where patient benefit needs to overshadow associated risks, especially since RA is publicly perceived as a non-life-threatening disease. Here, we provide an overview that focuses on advances in the application of gene therapy to RA over the last five years, including: novel targets and approaches; the viral and non-viral applications most likely to succeed in the clinic; advances in our understanding of the contralateral effect; the latest successes with anti-inflammatory cytokines; and a review of advancements towards clinical trials.
18395771 Lipid profiles in patients with rheumatoid arthritis: mechanisms and the impact of treatme 2009 Apr OBJECTIVE: To describe the impact of rheumatoid arthritis (RA), and its treatment, on lipoprotein levels with potential implications for atherosclerosis. METHODS: A PubMed literature search was undertaken for studies published between 1990 and May 2007, using the search terms "rheumatoid arthritis" AND "lipid" OR "lipoprotein," and including all relevant drug treatment terms for glucocorticoids, disease-modifying antirheumatic drugs, and biologics. RESULTS: Patients with RA face an increased risk of developing premature cardiovascular disease and limited ability to modify risk factors, eg, through exercise. RA is associated with an abnormal lipoprotein pattern, principally low levels of high density lipoprotein (HDL) cholesterol. Most treatments for RA tend to improve the atherogenic index (total/HDL cholesterol ratio), with more evidence for biologics in this regard. The improvement in the lipoprotein profile in RA appears to be associated with suppression of inflammation. CONCLUSIONS: Lipid levels should be monitored and managed in patients with RA to minimize the long-term risk of cardiovascular disease. More research is needed to quantify the relationship between systemic inflammation and lipoprotein levels and to determine the impact of specific lipoprotein particles, eg, small dense low-density lipoprotein and subfractions of HDL on long-term risk. Control of inflammation may have an effect on modifying cardiovascular risk.
18234247 The role of physical activity in rheumatoid arthritis. 2008 May 23 Rheumatoid arthritis (RA) is a chronic inflammatory auto-immune disease, causing progressive damage to the musculoskeletal system. Many patients with RA also suffer from accelerated muscle loss or cachexia, which contributes to the loss of physical function and quality of life. Physical activity plays a central role in the management of the disease as it is essential to maintain muscle strength and endurance, range of motion and the ability to perform activities of daily life. On the other hand, given the nature of the disease, there is always an increased risk for injury. There is a large amount of literature investigating the effect of exercise interventions on muscle function and disease activity. These studies show that exercise clearly improves muscle function without affecting disease activity. Studies including radiographic evaluation of joint damage as an endpoint also show that there is no evidence that exercise, even high-intensity exercise, increases inflammation or joint damage, although care should be taken with patients with severe baseline damage. Regarding daily physical activity (exercise is only one component of physical activity) there is hardly any research done showing either that physical activity is indeed decreased in patients or whether or not there is a relation between daily physical activity and disease activity. The results from studies looking at the effect of exercise on muscle mass or the ability to prevent or reverse cachexia are somewhat contradictory, but it seems that when the training dose is sufficiently large, gains in muscle mass can be achieved.
19524171 Vascular disease in rheumatoid arthritis: from subclinical lesions to cardiovascular risk. 2009 Jul Rheumatoid arthritis (RA) is one of the most prevalent and complex inflammatory diseases affecting primarily the joints, but also associating several extra-articular features. The vascular disease in RA encompasses a large spectrum of lesions, from rheumatoid vasculitis to atherosclerotic lesions. During the last years the importance of the vascular disease related to atherosclerosis in terms of cardiovascular morbidity and global mortality became evident in RA. The inflammatory hypothesis of atherosclerosis in RA implies that mediators originating from the inflamed synovial tissue or from the liver may have systemic vascular consequences, leading to endothelial dysfunction and structural abnormalities of the vessels. Hence, the global management of patients with RA must include the improvement of cardiovascular risk in parallel with the management of joint disease.
16622478 B-cell targeting in rheumatoid arthritis and other autoimmune diseases. 2006 May B-cell-targeted therapy for autoimmune disease emerged from theoretical proposition to practical reality between 1997 and 1998, with the availability of the B-cell-depleting monoclonal antibody rituximab. Since then, a score of autoantibody-associated disorders have been treated, with most convincing evidence of efficacy seen in subjects with rheumatoid arthritis. Several classes of B-cell-targeted agent are now under investigation. From the outset, a major goal of B-cell targeting has been the re-establishment of some form of immunological tolerance. In some subjects, the observed improvement of disease for years following therapy fuels hope that this goal might ultimately be achievable.
18554149 MAPK phosphatases as novel targets for rheumatoid arthritis. 2008 Jul BACKGROUND: Rheumatoid arthritis (RA) represents a challenge for therapeutic interventions due to complex inflammatory signalling pathways underlying its pathogenesis. The MAPK signalling network, a major effector limb of the inflammatory lesion, is an attractive therapeutic target. MAPK phosphatases (MKPs), endogenous negative regulators of MAPK signalling, have received increasing recognition as modulators of inflammatory and immune responses, and hence as a potential therapeutic avenue for RA. OBJECTIVE: To present the rationale for therapeutically targeting MAPK signalling and explore the case for addressing MKP1 as a novel therapeutic strategy for RA. METHODS: We summarise literature describing the importance of MAPK signalling in RA and review reports describing the roles of MKPs in modulating innate and adaptive immune responses. Finally we expand on the role of MKP1 in RA pathogenesis and explore data defining MKP1 as a mediator of glucocorticoid action. CONCLUSION: MKP1 constitutes an exciting, novel potential therapeutic target for RA.
18157733 The burden of rheumatoid arthritis and access to treatment: a medical overview. 2008 Jan As part of the investigation into the burden of rheumatoid arthritis (RA) and the access to treatment, this article reviews the medical aspects of the disease. RA is mediated by a variety of pathogenic events which culminate in the activation of B-cells, T-cells and other cell populations and lead to secretion of proinflammatory cytokines. These events result in signs and symptoms of active disease, such as pain and swelling, joint damage and disability, the three cornerstones of the clinical expression of RA. Active disease leads to joint damage and both to disability, whereby joint destruction is associated with the irreversible portion of disability. The diagnosis of RA is based on characteristic clinical and laboratory features, however, these may not be obvious in early disease. Therapy aims at interfering with disease activity, ideally leading to remission, as well as at retarding, ideally holding or even healing, joint destruction. This can be achieved by using disease modifying anirheumatic drugs (DMARDs). Among the chemical DMARDs, methotrexate is the anchor drug, although there exist many more such agents. Among the biological compounds, TNF-inhibitors have been in use for more than one decade, and co-stimulation blockade and B-cell targeted therapy have been recent additions to the armamentarium. Therapeutic outcome can be predicted by clinical means.
18557991 The need for prognosticators in rheumatoid arthritis. Biological and clinical markers: whe 2008 Rheumatoid arthritis is a heterogeneous disease with respect to clinical manifestations, serologic abnormalities, joint damage and functional impairment. Predicting outcome in a reliable way to allow for strategic therapeutic decision-making as well as for prediction of the response to the various therapeutic modalities available today, especially biological agents, would provide means for optimization of care. In the present article, the current information on biological and clinical markers related to disease activity and joint damage as well as for predictive purposes is reviewed. It will be shown that the relationship of many biomarkers with disease characteristics is confounded by factors unrelated to the disease, and that only few biomarkers exist with some predictive value. Moreover, clinical markers appear of equal value as biomarkers for this purpose, although they likewise have limited capacity in these regards. The analysis suggests the search for better markers to predict outcomes and therapeutic responsiveness in rheumatoid arthritis needs to be intensified.
18422737 Redox signalling and the inflammatory response in rheumatoid arthritis. 2008 Jun Reactive oxygen species (ROS) are produced mainly during oxidative phosphorylation and by activated phagocytic cells during oxidative burst. The excessive production of ROS can damage lipids, protein, membrane and nucleic acids. They also serve as important intracellular signalling that enhances the inflammatory response. Many studies have demonstrated a role of ROS in the pathogenesis of inflammatory chronic arthropathies, such as rheumatoid arthritis. It is known that ROS can function as a second messenger to activate nuclear factor kappa-B, which orchestrates the expression of a spectrum of genes involved in the inflammatory response. Therefore, an understanding of the complex interactions between these pathways might be useful for the development of novel therapeutic strategies for rheumatoid arthritis.
17625943 Pathophysiological links between rheumatoid arthritis and the Epstein-Barr virus: an updat 2007 Oct Numerous associations have been documented between the Epstein-Barr virus (EBV) and rheumatoid arthritis (RA). Thus, anti-EBV antibody titers are higher in RA patients than in healthy controls. Lymphocytes from RA patients show impaired responses to EBV. Several EBV antigens share similarities with self antigens; more specifically, the glycine/alanine repeats in EBNA-1 resemble synovial proteins and the EBV gp110 glycoprotein contains a copy of the shared epitope. Cell-mediated responses to EBV replicative cycle proteins and to gp110 have been documented in joint fluid from RA patients. In situ hybridization and PCR techniques have identified EBV antigens and genetic material within the rheumatoid synovium, albeit with variable yields. The EBV burden in peripheral blood mononuclear cells is higher in RA patients than in controls. EBNA-1 can undergo citrullination, and the EBV can induce antibodies to citrullinated peptides. RA patients are at increased risk for lymphoma, including EBV-associated lymphoma. Despite these multiple and complex links between EBV and RA, proof of a causal association is lacking. EBV infection may contribute indirectly to the pathophysiology of RA by impairing immune control of EBV replication, causing increased exposure to EBV antigens and, thereby, chronic inflammation. The effect of biotherapies for RA on EBV-host relations needs to be investigated.
17009815 The distal radioulnar joint in rheumatoid arthritis. 2006 Aug Rheumatoid arthritis (RA) involves the wrist in up to 80% of cases; up to 95% of patients have signs of wrist arthritis after 12 years of disease. The distal radioulnar joint (DRUJ) is involved in 31% to 75% of these patients and is often the first compartment of the wrist involved. The inflammatory sequence of events leads to the "caput ulnae syndrome" described by Backdahl in 1963. Extensor tendon ruptures are frequently associated. The presence of the "scallop" sign on radiographs is an alerting sign for tendon attrition. The gold standard in treatment remains resection of the distal ulnar head, known as Darrach's procedure. The most frequent complication is instability of the proximal ulnar stump. In order to restore stability or to prevent instability, several stabilisation techniques have been reported with free tendon grafts, the extensor carpi ulnaris, the flexor carpi ulnaris, the joint capsule and the pronator quadratus muscle. There is no evidence that stabilisation of the proximal ulnar stump during the initial operation gives better results. Another drawback of ulnar head resection is the progression of ulnar translation of the carpus. There are however several surveys showing that this ulnar translocation is the consequence of the disease rather than the result of the Darrach procedure. Several features such as an increased radial slope (> 23 degrees) and/or destruction of the ulnar corner of the distal radial epiphysis have been mentioned as predictive elements for further ulnar slide of the carpus. The Sauvé Kapandji procedure is in these cases a useful alternative choice. Another advantage of this technique is that it provides a larger surface so that other (radial) procedures can be more easily combined (Chamay partial radiocarpal fusion, wrist prosthesis).
16670812 [Pregnancy in patients with rheumatoid arthritis and inflammatory spondylarthropathies]. 2006 May The activity of a rheumatic disease can be influenced by pregnancy and puerperium. Prospective studies have shown an improvement in joint involvement in rheumatoid arthritis in two thirds to three quarters of pregnancies. After birth, an exacerbation is common. In spondylarthropathies there is no relevant change in disease activity. The fetal outcome is not impaired in patients with rheumatoid arthritis and inflammatory spondylarthropathies. Every pregnancy in women with a rheumatic disease should be considered as high-risk, and such pregnancies require close collaboration between rheumatologists and obstetricians.
17533688 Role of ultrasound in assessment of early rheumatoid arthritis. 2007 Apr This report reviews imaging methods used for diagnosis and monitoring of rheumatoid arthritis, with emphasis on the role of ultrasonography. Traditionally, conventional radiography has been useful in detecting and monitoring the extent of joint destruction in rheumatic disease. However, it is particularly difficult to detect pathological joint changes in the early stages. Magnetic resonance imaging is able to detect inflammation of the synovial membrane and erosions but is limited by cost and availability. Ultrasound has recently emerged as a useful and potentially reliable method for assessing the degree of joint inflammation and erosion in patients with early rheumatoid arthritis.
18957873 Efficacy of biologicals in the treatment of rheumatoid arthritis. a meta-analysis. 2009 Rheumatoid arthritis (RA) is a chronic multisystem disease. A characteristic feature of RA is persistent inflammatory synovitis, usually involving the peripheral joints in a symmetric distribution. The prevalence of RA is approximately 0.8% of the population (range: 0.3-2.1%); women are affected approximately 3 times more often than men. The current therapeutic approach is to start a disease-modifying agent early in the illness to prevent eventual joint damage. Older disease-modifying anti-rheumatic drugs include methotrexate, sulphasalazine and hydroxychloroquine. Newer ones such as leflunomide and cyclosporin are also used. A recent advance in the management of rheumatoid arthritis is the use of biological agents, which block certain key molecules involved in the pathogenesis of the illness. They include tumour-necrosis-factor-alpha-blocking agents such as infliximab, etanercept and adalimumab, the anti-CD-20 agent, rituximab, and CTLA-4 Ig abatacept. The present study was planned with the aim of evaluating the efficacy of such newer biological therapies in refractory RA at various time points. Databases including Medline, Embase and the Cochrane Library were searched for all relevant studies up to January 2007. A total of 26 studies were included in present meta-analysis. The method of DerSimonian and Laird [Control Clin Trials 1986;7:177-188] was used to calculated a pooled odds ratio (OR) for the American College of Rheumatology (ACR) criteria 20, 50 and 70, at 24, 54 and 96 weeks. The overall pooled OR were found to be significantly more than the placebo at all 3 time points for all 3 criteria (ACR 20, 50 70). In conclusion, biologicals as a group are highly effective in the treatment of RA. Biologicals were efficacious both in treatment naïve and methotrexate-refractory patients.
18783741 Challenges in the management of rheumatoid arthritis in developing countries. 2008 Aug Rheumatoid arthritis (RA) is a systemic autoimmune disease which is characterized by chronic inflammation of the joints. Patients experience chronic pain and suffering, and increasing disability; without treatment, life expectancy is reduced. It is imperative to identify patients early so that control of inflammation can prevent joint destruction and disability. Although great advances have been made in the developed nations, early diagnosis remains a great challenge for developing countries during the Bone and Joint Decade (2000-2010) and beyond. Developing countries face important and competitive social, economic, health- and poverty-related issues, and this frequently results in chronic diseases such as RA being forgotten in health priorities when urgent health needs are considered in an environment with poor education and scarce resources. Epidemiological studies in developing countries show a lower but still important prevalence in different regions when compared to that in Caucasians. It seems that the severity of RA varies among different ethnic groups, and probably starts at a younger age in developing countries. Practising rheumatologists in these regions need to take into account several important problems that include suboptimal undergraduate education, inadequate diagnosis, late referrals, lack of human and technical resources, poor access to rheumatologists, and some deficiencies in drug availability. Infections are very important in RA, and special care is needed in developing countries as some endemic infections include tuberculosis, human immunodeficiency virus (HIV), hepatitis B, and hepatitis C. These infections should be carefully taken into account when medications are prescribed and monitored. This chapter presents published information covering the main challenges faced in these environments, and suggests strategies to overcome these important problems in RA management.