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ID PMID Title PublicationDate abstract
9012755 Treatment of rheumatoid arthritis. 1997 Jan The management of rheumatoid arthritis (RA) remains a challenging objective. Recent trends have led to the earlier and more "aggressive" treatment of patients with active disease. This change in outlook is largely the result of the recognition that significant damage can occur fairly soon after the onset of disease. This article reviews the currently available therapies, including a discussion of the benefits and side effects associated with individual agents. In addition, possible approaches to the treatment of RA will be reviewed.
9031383 Pregnancy and rheumatoid arthritis. 1997 Feb Amelioration of rheumatoid arthritis (RA) occurs in about three quarters of pregnancies. Most women who improve experience initial relief in the first trimester. RA almost invariably recurs within 3 to 4 months of delivery. The effect of pregnancy upon the risk of first developing RA is similar in some respects but also differs from that observed in women with established disease. Analogous to women with established disease, the chance of a woman first developing RA is significantly reduced during pregnancy but increased in the first year post partum; thereafter risk is decreased. There is no indication of any adverse effects of RA on pregnancy outcome. Although limited, some medications can be used during pregnancy and during lactation without jeopardizing the well-being of the fetus.
11544014 Immunotherapy for rheumatoid arthritis. 2001 Oct Recently published studies confirm that the long-term use of biological agents targeting TNF-alpha in therapy for rheumatoid arthritis (RA) gives rise to sustained improvement in symptoms and signs of disease, and in the quality of life. Furthermore, it has emerged that anti-TNF therapy protects joints from structural damage, which unexpectedly is also observed in the patient population showing no apparent benefit in control of signs and symptoms. Therapeutic benefit is observed in established disease that is unresponsive to conventional DMARDS and in early DMARDS-naïve RA patients. Thus, for patients with RA, anti-TNF therapies set a new standard for symptom control and joint protection.
11358412 Is early rheumatoid arthritis the same disease process as late rheumatoid arthritis? 2001 Mar Thoughts on treatment for the early control of synovitis have stimulated research on pathobiological events at the site of inflammation in patients with early rheumatoid arthritis. Several studies have thus been conducted to examine synovial biopsy samples at various stages of the disease. The most important conclusion from these studies is that all features of chronic synovial inflammation can be observed in so-called early rheumatoid arthritis. This suggests that no arguments exist for the effect of therapeutic intervention on synovitis varying in different phases of rheumatoid arthritis. In end-stage rheumatoid arthritis, factors that are secondary to the disease may contribute to the perpetuation of synovial inflammation. Mutations in key regulatory genes could play a role in the autonomous progression of the disease. In addition, it is conceivable that the release of bone and cartilage fragments might elicit an inflammatory response in patients with destructive rheumatoid arthritis.
11930852 Rheumatoid arthritis: a primary care approach. 2001 Sep PURPOSE: To provide primary care providers with guidelines on the evaluation, diagnosis and management of patients with rheumatoid arthritis (RA). DATA SOURCES: Research-based articles in the medical literature, review articles, and clinical practice is a chronic inflammatory disease that affects mainly synovial joints. Diagnosis is based primarily on clinical examination. Clinical criteria developed by the American Rheumatism Association can help the primary care provider recognize this potentially devastating disease and facilitate early referral to a rheumatologist for treatment. IMPLICATIONS FOR PRACTICE: Patients with RA should be treated early and aggressively. Laboratory tests are not essential to confirm the diagnosis of RA. The clinical usefulness of the rheumatoid factor could be increased by restricting the test to patients who have a high probability of RA based on clinical symptoms.
11396098 Rheumatoid arthritis. From bench to bedside. 2001 May In the last decade, basic science has unraveled in considerable detail the inflammatory and related processes ongoing in RA synovial membrane. This has translated to cytokine targeting therapies with some effect. How much more can be achieved? It may be argued that the order of improvement obtained thus far obviates further study. This ignores the potential to achieve a far greater magnitude of disease suppression. Our objective in innovating biologic therapies should now be routine achievement of American College of Rheumatology "70% responses" or disease remission and design of patient-specific therapy based on individual disease characteristics. We have not yet explored the potential contained in combination biologic approaches, particularly when different processes within the disease are targeted. Cocktails might target T cells, cytokines, and angiogenic factors, for example. These developments must also be seen in the context of the information soon to be available from the Human Genome Project. The impact of gene array analysis and similar techniques that facilitate simultaneous evaluation of thousands of gene activation events is also awaited. This, in turn, is likely to require considerable development in our use of information technology, because the volume of information will soon (or may already) be prohibitive. Finally, encompassing genomic and bioinformatic approaches should certainly challenge our basic diagnostic criteria such that it ultimately may be necessary to consider our clinical diagnoses on the basis not only of clinical phenotype but of genotype and biologic response profile. Through this rapid evolution, close communication between physician and scientist is essential.
9494992 Rheumatoid arthritis of the ankle and hindfoot. 1998 Feb Rheumatoid arthritis frequently affects the hindfoot and ankle and may present a considerable source of dysfunction. Awareness of characteristic clinical and radiographic findings and other diagnostic modalities help the clinician to evaluate the progression of the disease and determine the best methods of management. A variety of nonoperative treatments may slow progression of deformities, improve function, and provide symptomatic relief. If these measures fail, surgical intervention, including soft-tissue procedures as well as a variety of arthrodesis techniques, can return patients to a more active lifestyle.
10332134 Rheumatoid arthritis: a review and suggested dental care considerations. 1999 May BACKGROUND: Rheumatoid arthritis, or RA, is a chronic multisystem disease of presumed autoimmune etiology. It is estimated that arthritis and other rheumatic conditions affect 42.7 million Americans. Medical complications due to RA and its treatment may affect the provision of oral health care. METHODS: The authors undertook an extensive review of the English literature relating to RA and dental care. They used primarily MEDLINE searches, which included such key words as "rheumatoid arthritis" and "dental care" and subsequent appropriate subheadings. While the MEDLINE search spanned the years from 1975 to the present, the most recent literature was prioritized. Appropriate medical and dental textbooks were also used. The authors extrapolated information from selected texts based on its relevance to dentistry, oral health and the role of the dental provider in the overall treatment of RA patients. RESULTS: The authors reviewed nearly 200 articles and seven textbooks. Their determination of the texts' relevance to oral health care was based on content, significance, quality, journal in which articles were published and year of publication. Major features of RA--including its diagnosis, pathophysiology, clinical features and medical treatment--were identified, as well as complications due to treatment modalities and various related oral manifestations and conditions. CONCLUSIONS: Medical complications due to RA and its treatment can affect oral health care. Oral health care providers need to recognize and identify modifications of dental care based on the medical status of patients with RA. Furthermore, oral health care providers play an important role in the overall care of these patients as it release to early recognition, as well as control of the disease. CLINICAL IMPLICATIONS: In most patients with RA, the condition will necessitate few or no changes in routine dental care. However, considerations include the patient's ability to maintain adequate oral hygiene, xerostomia and its related complications, the patient's susceptibility to infections, impaired hemostasis, and untoward drug actions and interactions. Patients with RA may require antibiotic prophylaxis owing to joint replacement and/or immune suppression, glucocorticosteroid replacement therapy and modifications in oral hygiene procedures. Intra- and extraoral conditions such as ulcerations, gingival overgrowth, disease-associated periodontitis and temporomandibular pathology also need to be recognized.
9437637 Rheumatoid arthritis: current clinical and research directions. 1997 Dec Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by synovitis and joint erosions. It affects approximately 1% of the adult population in a female/male ratio ranging from 2:1 to 4:1. RA is an insidious disease, typically having an onset of symmetric joint swelling and reaching a peak incidence in the fourth and fifth decades. Extraarticular manifestations include pulmonary, ocular, and vascular disease. The etiology of RA remains unknown. Attempts to discover infectious causes have proven unsuccessful, although environmental influences may trigger a response leading to the development of this autoimmune disease. Genetic associations have been identified, particularly with the major histocompatibility complex class II antigens. Furthermore, twin studies have shown a 30%-50% concordance rate for monozygotic twins. Approximately 70%-80% of patients with RA have rheumatoid factor present in the blood, although its role remains unclear. Hormonal status may influence RA. The majority of RA patients are women, and in 75% of them, the disease improves during pregnancy. RA has significant financial and social implications associated with treatment costs, lost wages, disability, and increased mortality. Mainstays of medical therapy have included nonsteroidal anti-inflammatory and immunosuppressive agents, such as prednisone and methotrexate. Recent advances in the treatment of RA include specific inhibitors of cyclooxygenase II, T cells, blood vessels, cytokines (such as tumor necrosis factor-alpha [TNF-alpha] or interleukin-1 [IL-1]), and adhesion molecules. Additional studies are ongoing with combination interventions. It is anticipated that a better understanding of the basic pathophysiologic mechanisms critical in RA pathogenesis will provide more precise and efficacious therapy.
10193682 Is there a role for antibiotics in the treatment of patients with rheumatoid arthritis? 1999 Mar Despite many advances in the understanding and treatment of rheumatoid arthritis, its pathophysiology remains incompletely understood. An infectious aetiology of rheumatoid arthritis has long been postulated but, even though many continue to believe that there is a 'triggering agent for rheumatoid arthritis', none has been identified. Currently, both sulfasalazine and minocycline have been shown to be effective treatments for rheumatoid arthritis and are being used increasingly. In the case of minocycline, it appears that its ability to inhibit metalloproteases is an important characteristic that may account for some or part of its action against rheumatoid arthritis. Whether the antibacterial effects of these drugs or others are important in the treatment of rheumatoid arthritis continues to be investigated.
11727837 Treatment of rheumatoid arthritis in the third millennium. 2001 Immense progress has been made in recent years in the management of patients with autoimmune diseases, such as rheumatoid arthritis (RA). This progress is largely owed to the advances in our understanding of cellular and molecular mechanisms involved in the pathogenesis of inflammation and autoimmunity and the substantially improved knowledge of molecular biology. In this editorial review, we delineate recent developments in the treatment of RA with a focus on biological therapeutics. we outline the concerns and open questions risen by the current studies and we portray future expectations based on the recent observations from those trials with biological treatment interventions.
9588280 Rheumatoid arthritis--a review. 1998 Jan Rheumatoid arthritis, a common chronic inflammatory arthritis, tends to run a more benign course in patients from the community than those seen at hospitals. The aetiology is unknown but the disease is postulated to result from the interaction between genetic and environmental factors. The strongest genetic association is with the major histocompatibility complex (MHC) Class II antigen HLA DR 4, although not more than 50% of the genetic susceptibility is due to MHC genes. In early disease the pathogenesis is thought to be T cell mediated whereas in late disease the mechanisms are T cell independent, with destruction contributed to by autonomous fibroblast like synoviocytes. The diagnosis is made on clinical groups. Management is directed at controlling active synovitis so that joint damage is limited. The early use of a slow acting anti-rheumatic drug is now advocated, as studies have shown that they can potentially prevent or limit the progression of disease. Biological therapies are still experimental but may hold promise for the future.
9494991 The knee joint in rheumatoid arthritis. 1998 Feb The knee joint is commonly damaged in polyarticular rheumatoid arthritis. Surgical management depends on the preservation of the articular cartilage and degree of synovitis. Arthroscopic synovectomy is performed in intractable synovitis with cartilage sparing. Technique of total knee replacement is more complex because of bone and soft-tissue damage in rheumatoid arthritis, and complications are more common, particularly infection. Overall, long-term results with knee arthroplasty have been excellent in rheumatoid arthritis, with improved function and reduction in pain in the vast majority of patients.
11358414 How do you diagnose rheumatoid arthritis early? 2001 Mar There are difficulties in making an accurate diagnosis of rheumatoid arthritis in its early stages, a principal problem being the fact that its most defining feature is chronicity, which, by definition, takes time to identify. There is substantial evidence that patients with rheumatoid arthritis should be treated early, and the majority are now commenced on therapy when first diagnosed. A logical implication of the early therapy approach is that treatment before rheumatoid arthritis is fully developed may have even greater benefits. This requires patients who are likely to have a persistent, more severe disease to be identified and treated effectively in the very earliest stages. This requires a system of the early specialist referral of suitable patients and the use of effective predictors of patient outcome. This text discusses the early arthritis clinic approach and the current evidence base available for use in constructing management guidelines for such patients.
9651073 Monoclonal antibody therapy in rheumatoid arthritis. 1998 May Monoclonal antibodies bind to their targets with high specificity and therefore have excellent potential as therapeutic agents. Biotechnological advances have allowed the production of large quantities of engineered monoclonal antibodies for therapeutic use. Recent research in rheumatoid arthritis has identified important mediators of synovitis. Monoclonal antibodies targeting these have been tested in clinical trials over the last decade. Anti-cytokine therapies, in particular anti-tumour necrosis factor alpha monoclonal antibodies, suppressed inflammation and produced rapid symptomatic improvement. Anti-lymphocyte monoclonal antibodies produced long-lasting disease suppression in animal models of rheumatoid arthritis. The use of depleting anti-lymphocyte monoclonal antibodies in rheumatoid arthritis had been disappointing as they did not penetrate the synovial joint in sufficient quantity to suppress disease without producing severe and protracted peripheral blood lymphopenia. Consequently, their use in rheumatoid arthritis had been abandoned. In contrast, clinical trials of non-depleting anti-CD4 monoclonal antibodies in rheumatoid arthritis showed that they could suppress synovitis. However, it remains unclear whether they could lead to prolonged disease improvement.
9428608 The molecular basis of rheumatoid arthritis. 1997 Nov Rheumatoid arthritis (RA) is an inflammatory disease targeting the synovial membrane and extra-articular tissues. The most feared consequences are significant levels of pain, functional disability, and rheumatoid organ involvement. Molecular investigations of RA have markedly changed the understanding of the pathogenesis although the etiology remains unresolved. Despite the failure of intense efforts to confirm the presence of an infectious micro-organism in rheumatoid synovium, the concept that RA is infectious in origin has continued to be attractive. Theories on the autoimmune nature of RA have benefited from the enormous progress made in understanding the cellular and molecular components of normal immune responses. However, convincing experimental evidence of a joint-specific endogenous antigen in the synovial lesions is still lacking. The viewpoint that RA represents the sequelae of systemic lymphoproliferation has recently been supported by the finding of autoreactive T cells with atypical growth and differentiation behavior. Significant cross-fertilization for the understanding of RA can be expected by studies elucidating cell cycle control and the role of proto-oncogenes. The realization that RA is a genetic disease has had and will have a major impact on investigating pathological events. As in other common genetic disorders, multiple genetic determinants contribute to the risk of an individual developing chronic inflammatory rheumatoid synovitis. Individual genetic elements are seldom mutated or abnormal, but a risk threshold is reached by their accumulation and combination. Genes encoded in the HLA region are recognized as RA risk genes. Recent studies have emphasized that a gene dosing effect for RA-associated HLA alleles is functional, and that HLA polymorphisms act as progression factors rather than as initiation factors in the disease process. These data have challenged the traditional paradigm that disease-associated HLA molecules function solely through their capability to select, bind, and present an arthritogenic antigen. Current efforts focus on identifying the spectrum and nature of genes associated with various RA phenotypes. The future will likely see a broadening of biological systems involved in the pathogenesis of RA with anomalies other than immunoresponsiveness contributing to mechanisms driving articular and extra-articular RA.
12086312 Arthritis induced in rats with nonimmunogenic adjuvants as models for rheumatoid arthritis 2001 Dec Rat models are useful for studies of the pathogenesis of rheumatoid arthritis (RA) since rats are extraordinarily sensitive to induction of arthritis with adjuvants. Injection of not only the classical complete Freund's adjuvant but also mineral oil without mycobacteria and pure adjuvants such as pristane and squalene, induce severe arthritis in many rat strains. Models like pristane-induced arthritis in rats are optimal models for RA since they fulfill the RA criteria including a chronic relapsing disease course. Arthritogenic adjuvants like pristane, avridine, squalene and mineral oil are not immunogenic since they do not contain major histocompatibility complex (MHC) binding peptides. Nevertheless, the diseases are MHC-associated and dependent on the activation of alphabetaTCR (T-cell receptor)-expressing T cells. However, it has not been possible to link the immune response to joint antigens or other endogenous components although immunization with various cartilage proteins induce arthritis but with different pathogeneses. To unravel the mechanisms behind adjuvant-induced arthritis, a disease-oriented genetic approach is optimal. Several loci that control onset of arthritis, severity and chronicity of the disease have been identified in genetic crosses and most of these have been confirmed in congenic strains. In addition, many of these loci are found in other autoimmune models in the rat as well as associated with arthritis in mice and humans.
9769352 Rheumatoid arthritis: a case study. 1998 Dec Rheumatoid arthritis (RA) is a chronic, systemic, progressively deteriorating, connective tissue disease characterized by inflammation of the synovial membrane of the joints, pain, immobility, and fatigue. Exacerbations of RA are frequently associated with periods of physical and/or emotional stress. It is estimated that 1 in every 100 persons throughout the world suffers from RA. In the United States, women have 2 to 3 times the incidence rate of men, with no significant radical differences noted between Caucasians and African-Americans. In this article a case study format is used to provide information pertaining to the diagnosis and treatment of the adult RA patient.
11478346 Early rheumatoid arthritis: can we predict its outcome? 2001 Apr The continuing trend towards more aggressive treatment of rheumatoid arthritis (RA) has seen an increasing interest in the early phase of this chronic inflammatory disease. Optimal benefit from present and emerging therapies is limited by our prognostic abilities during this period. The present review attempts to outline first the many methodological issues encountered in studies of early RA, and second the extent to which each major outcome measure can be explained, both by readily available clinical variables and by HLA-DR genotyping. The evidence supporting the clinical usefulness of genotyping is discussed separately. Based on this information, a clinically appropriate approach to the management of early RA and the identification of patients suitable for experimental therapies is suggested.
11234674 [Gene transfer immunotherapy in rheumatoid arthritis: perspectives]. 2001 Feb INTRODUCTION: Tumor necrosis factor (TNF) blocking agents have changed the therapeutic approach in rheumatoid arthritis, but a true clinical remission remains rare. Gene therapy opens new perspectives in immunotherapy in rheumatoid arthritis. This review focuses on the research, data and clinical development in rheumatoid arthritis using this strategy. CURRENT KNOWLEDGE AND KEY POINTS: New therapeutical targets have been described besides the cytokine inhibitors: apoptosis inducers, angiogenesis inhibitors and metalloprotease inhibitors, cell activation and signalization have been used in experimental models to inhibit arthritis. Gene therapy makes it possible to better understand the physiopathology of rheumatoid arthritis and offers the opportunity to induce true remissions of experimental arthritis. FUTURE PROSPECTS AND PROJECTS: Biotechnology allows the development of new safer vectors which permit long-term expression. However, the difficulties to produce high titers and safe vectors limit the use of this strategy. The previous clinical data on gene therapy in rheumatoid arthritis are limited to feasibility studies. We believe that the efficiency of gene therapy will be obtained by combining two or more complementary targets.