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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
12010607 Pathogenesis of bone lesions in rheumatoid arthritis. 2002 Jun Histopathologic characterization of bone erosions from patients with rheumatoid arthritis (RA) and studies performed in animal models of inflammatory arthritis provide strong evidence that osteoclasts play an important role in focal marginal and subchondral bone loss in inflammatory arthritis. Much has been learned concerning the factors responsible for the induction and activation of osteoclasts associated with the bone erosions in RA. Therapies that target these osteoclast-inducing factors or other aspects of osteoclast-mediated bone resorption represent potential targets for blocking or at least attenuating bone destruction in RA. The demonstration of the role of the newly described osteoclastogenic factor receptor activator of nuclear factor kappaB ligand in RA synovial tissues and the successful prevention of bone erosions in animal models of arthritis with its inhibitor osteoprotegerin provide hope that specific therapies can be developed for preventing bone and joint destruction in RA, particularly in situations in which disease-modifying agents are ineffective in controlling disease activity.
15261344 Apoptosis in rheumatoid arthritis: friend or foe. 2004 Aug A better understanding of the mechanisms that contribute to the resistance of synovial macrophages and fibroblasts to apoptosis will not only provide better insights into the mechanisms contributing to the perpetuation of rheumatoid arthritis (RA) but will also help identify targets for the development of novel, more effective, and long-lasting therapies for the treatment of patients with RA. To avoid toxicity, such as the induction of apoptosis of critical organs, the mechanisms by which these molecules are targeted and therapy delivered must be carefully selected, using the insights obtained from studies characterizing the mechanisms that promote chronic inflammation.
12848982 Sex hormones and rheumatoid arthritis. 2002 Oct Sex hormones are implicated in the immune response, with estrogens as enhancers at least of the humoral immunity and androgens and progesterone as natural immune-suppressors. In male rheumatoid arthritis (RA) patients, androgen replacement seems to ameliorate the disease and supports their involvement in the pathophysiology of the disease. The combination of androgens with cyclosporin A or methotrexate has been found to potentiate the apoptosis of monocytic inflammatory cells as well as to reduce the cell growth at least in vitro. Considerable interest has been devoted in the last years as to whether the use of oral contraceptive pills (OCs) may have a protective effect on the risk of RA. The results of many controlled studies have been found contradictory. At the present time, no consensus has been achieved regarding OCs administration and its relationship to the prevention or development of RA. In addition, an association of estrogen receptor gene polymorphism with age at onset of RA has been observed and might further explain inter-individual clinical and therapeutical-response variations. Local increased estrogen concentrations and decreased androgen levels have been observed in RA synovial fluids and seem to play a more important role in the immune/inflammatory local response.
11934345 Pharmacoeconomics of long-term treatment of rheumatoid arthritis. 2002 Apr Rheumatoid arthritis affects ~ 1% of the population. It is associated with pain, deformity, decreased quality of life and disability that in turn affects patients' ability to work. A variety of disease-modifying antirheumatic drugs are available to control the disease activity of rheumatoid arthritis. The goal of treatment is to improve patients' quality of life and prevent joint destruction. This paper reviews both the clinical aspects of frequently prescribed disease-modifying antirheumatic drugs and the available cost-effectiveness information. Clinical evidence supports the effectiveness of methotrexate, etanercept, infliximab, gold, hydroxychloroquine, leflunomide, sulfasalazine, penicillamine, cyclosporin, azathioprine and corticosteroids. The last four of these are associated with greater toxicity and are only used if less toxic drugs are ineffective. The lack of published economic evaluations of disease-modifying antirheumatic drugs highlights the need for such studies to allow efficacious and cost-effective drugs to be used to prevent the long-term complications of uncontrolled rheumatoid arthritis.
14969152 [Ultrasonography of the hand in rheumatoid arthritis]. 2003 Nov Authors present the ability of ultrasonography and Color and power Doppler sonography in evaluation of the hand structures in patients with rheumatoid arthritis. Imaging of bony contours allows to identify bone erosions. Thickness, oedema and presence of increased blood flow (hyperaemia) in the synovium in joints and tendon sheaths are characteristic features of an active inflammation. Changes of the tendon structure indicate its damage. US allows to image the carpal tunnel structures, to visualise changes of the median nerve in the carpal tunnel syndrome and gives possibilities to find the cause of its compression.
15049525 Advanced imaging of early rheumatoid arthritis. 2004 Jan Advances in MR imaging of arthritis include contrast-enhanced, dynamic, and quantitative imaging techniques. These advances may result in MR imaging becoming the gold standard in diagnosing early RA. MR imaging is a useful technique in diagnosis, follow-up, and evaluation of remission in rheumatic diseases of the joints. Early diagnosis of RA, in the first 6 months after the onset of symptoms, may lead to earlier control and prevent future erosions and deformities.
12110149 Why do we not have a cure for rheumatoid arthritis? 2002 There are currently unprecedented opportunities to treat rheumatoid arthritis using well-designed, highly effective, targeted therapies. This will result in a substantial improvement in the outcome of this disorder for most affected individuals, if they can afford these therapies. Yet our lack of understanding of the basic mechanisms that initiate and sustain this disease remains a major obstacle in the search for a definitive cure. It is possible, if not likely, that our best approach will be to identify individuals at risk and devise reliable, safe methods of preventing the disease before it occurs. The means to do this are currently unknown but should serve as a major focus of research.
12100639 Pain and quality of life among older people with rheumatoid arthritis and/or osteoarthriti 2002 Jul The aim of this study was to review the research literature on pain and quality of life (QoL) and the relationship between these variables among people aged 75 years and above with rheumatoid arthritis and/or osteoarthritis. A Medline and CINAHL search was carried out using MeSH terms rheumatoid arthritis, osteoarthritis, QoL and pain in various combinations. Seventeen articles were identified that met the requirements for methodological quality and inclusion criteria. No study focused only on respondents aged 75 years or over. The studies had varying representation of this age group. Pain was common in both groups and was found to increase with age and disease duration among those with rheumatoid arthritis but not among those with osteoarthritis. Increased pain could lead to depression. Pain, functional limitation and increased age were found to decrease QoL among those with rheumatoid arthritis and osteoarthritis alike. Social support was found to buffer against negative effects on QoL among those with osteoarthritis while no moderating effects were found in rheumatoid arthritis. Increased age was found to relate to pain (rheumatoid arthritis) and decrease QoL (both rheumatoid arthritis and osteoarthritis). It is, however, hard to draw any firm conclusions about older people's pain and QoL because of the lack of studies including respondents aged 75 years or over. Thus, research about pain and QoL, especially focusing on the old and the very elderly with rheumatoid arthritis/osteoarthritis, is needed. It also seems justified to say that nursing care should especially focus on older people and that these people should be assessed for their level of pain, functional limitations and QoL especially in the case of having rheumatoid arthritis and/or osteoarthritis.
15201941 Therapeutic gene transfer for rheumatoid arthritis. 2004 Jan Rheumatoid arthritis (RA) is a severe autoimmune systemic disease. Chronic synovial inflammation results in destruction of the joints. No conventional treatment is efficient in RA. Gene therapy of RA targets mainly the players of inflammation or articular destruction: TNF-alpha or IL-1 blocking agents (such as anti-TNF-alpha monoclonal antibodies, soluble TNF-alpha receptor, type II soluble receptor of IL-1, IL-1 receptor antagonist), anti-inflammatory cytokines (such as IL-4, IL-10, IL-1), growth factors. In this polyarticular disease, the vector expressing the therapeutic protein can be administered as a local (intra articular injection) or a systemic treatment (extra articular injection). All the main vectors has been used in experimental models, including the more recent lentivirus and adeno-associated virus. Ex vivo gene transfer was done with synovial cells, fibroblasts, T cells, dendritic cells, and different cells from xenogenic origin. In vivo gene therapy is simpler, although less controlled method. Clinical trials in human RA has started with ex vivo retrovirus expressing IL-1 receptor antagonist and have demonstrated the feasibility of the strategy of gene therapy. The best target remains to be determined and extensive researches have to be conducted in pre-clinical studies.
12389276 Rheumatoid arthritis of the cervical spine: current techniques for management. 2002 Apr The incidence of rheumatoid arthritis in the European and North American population is significant. Rheumatoid arthritis can result in serious damage to the cervical spine and the central neuraxis, ranging from mild instability to myelopathy and death. Aggressive conservative care should be established early. The treating physician should not be lulled into a false sense of security by reports suggesting that cervical subluxations are typically asymptomatic [76-78]. Gradual spinal cord compression can result in severe neurologic deficits that may be irreversible despite appropriate surgical intervention when applied too late. [figure: see text] The treatment of rheumatoid disease in the cervical spine is challenging. Many details must be considered when diagnosing and attempting to institute a treatment plan, particularly surgical treatment. The pathomechanics may result in either instability or ankylosis. The superimposed deformities may be either fixed or mobile. The algorithm suggested by the authors can be used to navigate through the numerous details that must be considered to formulate a reasonable surgical plan. Although these patients are [figure: see text] frail, an "aggressive" surgical solution applied in a timely fashion yields better results than an incomplete or inappropriate surgical solution applied too late. When surgical intervention is anticipated, it should be performed before the development of severe myelopathy. Patients who progress to a Ranawat III-B status have a much higher morbidity and mortality rate associated with surgical intervention than do patients who ambulate. Although considered aggressive by some, "prophylactic" stabilization and fusion of a [figure: see text] relatively flexible, moderately deformed spine before the onset of severe neurologic symptoms may be reasonable. This approach ultimately may serve the patient better than "observation" if the patient is slowly drifting into a severe spinal deformity or shows signs of early myelopathy or paraparesis.
15338253 [Therapy of cervical rheumatoid arthritis]. 2004 Aug The rheumatoid involvement of the cervical spine can be divided into three phases. In the early stage of the disease there is an isolated atlantoaxial subluxation (AAS), followed by vertical instability and subaxial instability. If patients show clear symptoms of cervical myelopathy, which can occur during any stage of the disease, the progression cannot be stopped by conservative treatment, which is of great importance at the beginning of the cervical manifestation. Patient education, physiotherapy and immobilization with a stiff collar can significantly reduce pain. Early and effective DMARD therapy can have a positive effect on the natural history of the disease. In case of progressive instability, cervical myelopathy or severe pain operative treatment is indicated. If there is an isolated AAS, fusion can be restricted to the C1/C2 segment. The Magerl transarticular screw fixation is the preferred technique for stabilization. If there is evidence for vertical instability or severe destruction of the C0/C1 joints, occipital cervical fusion has to be performed. Durin the preoperative planning it is necessary to look for signs of subaxial instability. If this is the case, fusion should include the entire cervical spine. Transoral decompression may be necessary when there is persistent anterior compression of the myelon, typically seen in fixed AAS. Non-ambulatory myelopathic patients are more likely to develop severe surgical complications. Therefore, it is important to avoid the development of severe cervical instability by early surgical intervention. The right timing for surgery is still a matter of controversy. Future prospective randomized trials should address this topic to improve the treatment concept for the rheumatoid patient.
15053455 Radiological progression in established rheumatoid arthritis. 2004 Mar Radiographic progression in established rheumatoid arthritis (RA) gives an objective measure of anatomical damage that defines the course of the disease and the longterm effects of treatment. This review defines the rate of joint damage, progression in individual joints, and predictive factors. Six longitudinal prospective studies of 103-378 RA patients followed for up to 20 years show that initially patients had less than 3% maximum possible damage, this rose to 11% maximal damage by 5 years and over 40% by 20 years. The rate of progression changed from an initial rate of 1.6% maximal progression annually to a later rate of 2.0% annually. Between 1977 and 1998 5 prospective studies of 40-147 hospital-based RA cases seen within 12 months of developing RA showed 60-73% of cases developed one or more erosions in the hands and wrists. However a community-based cohort of early RA patients reported, more recently showed 41% of 335 cases developed erosions. There are marked differences between joints. The wrists show most damage and in one series of 103 cases, by 20 years 18% of wrists were completely destroyed and only 25% were nonerosive. The same series showed ankle joints are rarely involved; at 20 years only 7 patients had major abnormalities with minor changes in 17 cases. Rheumatoid factor (RF) positivity is the dominant predictor of erosive damage. In one survey of 439 cases who presented with inflammatory polyarthritis, patients with an initial high RF had over twice the radiographic progression of seronegative cases. A further 8 studies, which enrolled 1395 patients, all show a strong link between radiolographic damage and RF status. The other key clinical predictor is disease activity indicated by surrogate measures such as the C-reactive protein (CRP) level. Suppressing disease activity judged by CRP levels not only decreases the progression of joint damage, but also may reduce new joint involvement to a greater extent than progression in already damaged joints. New potential markers of damage such as anticyclic citrullinated peptide ELISA tests may further improve the identification of those RA patients most at risk of erosive damage and, by implication, most in need of suppressive therapy.
12003371 The pathogenesis of rheumatoid arthritis: a guide to therapy. 2002 Apr The cause of rheumatoid arthritis (RA) is unknown; however, extensive research has yielded great insight into its pathogenesis. Lymphocytes play a significant role, but a lesser role in the perpetuation of late disease. The rheumatoid synovium is composed primarily of fibroblasts and monocytes that produce inflammatory cytokines, of which interleukin-1 and tumor necrosis factor are of key importance. Potential regulatory mechanisms balancing the effects of these cytokines are inadequate to prevent joint damage and subsequent disability. These cytokines seem responsible for stimulating destructive processes in the joint via induction of prostaglandins, angiogenesis, chemokines, adhesion molecules, osteoclastogenesis, and matrix metalloproteinases. This review discusses recent research findings in the immunopathogenesis of RA with respect to potential targets for therapy.
12163213 Cachexia in rheumatoid arthritis. 2002 Sep Rheumatoid arthritis is a debilitating, chronic, systemic, autoimmune disease of unknown etiology that causes destruction of joint cartilage and bone. It generally occurs between the fourth and sixth decades of life, and affects two to three times more women than men. It is characterized by joint stiffness, pain, and swelling, and is accompanied by a loss of body cell mass. This loss of cell mass, known as rheumatoid cachexia, predominates in skeletal muscle, but also occurs in the viscera and immune system. Thus, rheumatoid cachexia leads to muscle weakness and a loss of functional capacity, and is believed to accelerate morbidity and mortality in rheumatoid arthritis. Currently there is no established mechanism for rheumatoid cachexia, but it is accompanied by elevated resting energy expenditure, accelerated whole-body protein catabolism, and excess production of the inflammatory cytokines, tumor necrosis factor-alpha and interleukin-1beta. Tumor necrosis factor-alpha is probably the central mediator of muscle wasting in rheumatoid arthritis, and is known to act synergistically with interleukin-1beta to promote cachexia. In general, tumor necrosis factor-alpha and interleukin-1beta are thought to alter the balance between protein degradation and protein synthesis in rheumatoid arthritis to cause muscle wasting. The precise mechanism by which they do this is not known. Reduced peripheral insulin action and low habitual physical activity are important consequences of rheumatoid arthritis, and have also been implicated as mediators of rheumatoid cachexia. Insulin inhibits muscle protein degradation. Consequently, reduced peripheral insulin action in rheumatoid arthritis is thought to be permissive to cytokine-driven muscle loss. The cause of reduced peripheral insulin action in rheumatoid arthritis is not known, but tumor necrosis factor-alpha has been shown to interfere with insulin receptor signaling and is probably an important contributor. Low habitual physical activity has consistently been observed in rheumatoid arthritis and is an important consequence of, and contributor to, muscle wasting. In addition, low physical activity predisposes to fat gain and is believed to precipitate a negative reinforcing cycle of muscle loss, reduced physical function, and fat gain in rheumatoid arthritis, which leads to 'cachectic obesity'. To date, there is no standard treatment for rheumatoid cachexia. However, physical exercise is currently believed to be the most important and clinically relevant countermeasure against rheumatoid cachexia. In general, a combination of skeletal muscle strength training and aerobic exercise is recommended, but must be prescribed with the patient's disease status, overall health, and safety in mind. Future studies should investigate the safety, efficacy, and required dose of anti-cytokine therapy for the treatment of rheumatoid cachexia. In this review, we outline the current definition of rheumatoid cachexia, and discuss the etiology, pathogenesis, and treatment of rheumatoid cachexia.
15363872 Efficacy and safety of valdecoxib for treatment of osteoarthritis and rheumatoid arthritis 2004 Oct Our objective was to determine the efficacy and safety of valdecoxib (a cyclo-oxygenase 2 inhibitor) in the treatment of arthritis. Randomised, controlled trials comparing 10 or 20mg valdecoxib with placebo or non-steroidal anti-inflammatory drugs (NSAIDs) in patients with active osteoarthritis or rheumatoid arthritis. The manufacturer provided clinical trial reports. Data were combined through meta-analysis. Main outcomes were patient global rating of arthritis, arthritis pain, Western Ontario and McMaster Universities indices for osteoarthritis, American College of Rheumatology indices for rheumatoid arthritis, discontinuation, endoscopic ulcers, clinically significant upper gastrointestinal or renal events. Nine trials (five in osteoarthritis, four in rheumatoid arthritis) were included with 5726 patients. Overall, valdecoxib 10 and 20mg were superior to placebo and equivalent in efficacy to maximum daily doses of NSAIDs. Significantly fewer discontinuations because of gastrointestinal adverse events (4% versus 8%), or endoscopic ulcers of 3mm or more (5% versus 13%) occurred with valdecoxib compared with NSAIDs. Clinically significant upper gastrointestinal events occurred in 2/2733 (0.1%) with valdecoxib compared with 8/1846 (0.4%) with NSAIDs. Rates of clinically significant renal events were the same (2-3%) for valdecoxib and NSAIDs. At an appropriate dose valdecoxib was as effective as NSAIDs in osteoarthritis and rheumatoid arthritis. There were fewer gastrointestinal adverse event withdrawals and endoscopically detected ulcers. Convincing evidence of reduced major gastrointestinal adverse events could not be addressed by the trials.
15157000 Epidemiology and burden of illness of rheumatoid arthritis. 2004 Rheumatoid arthritis (RA) is a chronic, generally progressive autoimmune disease that causes functional disability, significant pain and joint destruction, and leads to premature mortality. It is estimated to affect between 0.5 and 1.0% of the adult population worldwide, increases in prevalence with age and affects more women than men. The magnitude of the severe long-term economic consequences of RA has been underestimated in the past. Most patients with the disease require continuous treatment to retard or stop progression and to control disease flares. Many also require surgery, such as total hip or knee replacement. In addition to these direct costs, work disability leads to reduced productivity and early retirement, and as a result, substantial indirect costs. The individual and his or her family must cope with the feeling of loss of contribution to society combined with redefined social roles, and the effects of pain, fatigue, low self-esteem, mental distress and depression. A number of countries in North America and Europe have reported a decline in the incidence of RA in recent years, although geographical differences remain that may be associated with genetic, environmental or cultural factors. Nevertheless, patients with RA have not shared the improvements in survival rates seen with other diseases over the last 40 years, and have a mean reduction in life expectancy of between 5 and 10 years. Disease severity, activity and disability are strongly linked to premature mortality in patients with RA. The high direct and indirect costs associated with RA, together with the substantial morbidity and mortality affecting millions of people worldwide, underline the potential benefits of improved treatments for this chronic disease to patients, their families and society.
12915154 Environmental factors and the outcome of rheumatoid arthritis. 2003 Oct The outcome of rheumatoid arthritis (RA) is influenced by both genetic and non-genetic (environmental) factors. Treatment is the most important environmental factor which influences RA outcome. This chapter considers non-treatment environmental influences on the outcome of RA. There is evidence that socio-economic factors (such as level of formal education and area of residence), smoking, diet and psychological factors may affect the levels of pain and physical disability experienced by RA patients. More work is needed in order to understand the mechanisms underlying these associations. Smoking may also adversely affect radiological outcome in the longer term. It is possible that pregnancy may improve the outcome of RA. Contrary to popular lay opinion, there is no evidence that the weather has any influence on RA.
15123035 Glucocorticoids in rheumatoid arthritis: a senescent research agenda on the brink of rejuv 2004 Feb Treatment of rheumatoid arthritis with glucocorticoids remains controversial despite a considerable and growing body of evidence. This chapter focuses on the research agenda in urgent need of execution: to define conclusively the benefit/harm trade-offs and pin down the place of these agents in the treatment cascade.
12110132 Humanized mice as a model for rheumatoid arthritis. 2002 Genetic susceptibility to rheumatoid arthritis (RA), a common autoimmune disease, is associated with certain HLA-DR4 alleles. Treatments are rarely curative and are often tied to major side effects. We describe the development of a humanized mouse model wherein new, less toxic, vaccine-like treatments for RA might be pretested. This model includes four separate transgenes: HLA-DR*0401 and human CD4 molecules, a RA-related human autoantigenic protein (HCgp-39), and a T-cell receptor (TCRalphabeta) transgene specific for an important HCgp-39 epitope, eliciting strong Th1 responses in the context of HLA-DR*0401.
12956651 Inter-relationships between rheumatoid arthritis and periodontal disease. A review. 2003 Sep This review considers the considerable similarities between periodontal disease and rheumatoid arthritis (RA). While the etiology of these two diseases may differ, the underlying pathogenic mechanisms are remarkably similar and it is possible that individuals manifesting both periodontitis and RA may suffer from a unifying underlying systemic dysregulation of the inflammatory response. In light of these findings, the implications for the use of disease-modifying medications in the management of these two chronic inflammatory conditions is apparent. Further longitudinal studies and medication-based intervention studies are required to determine just how closely these two conditions are allied.