Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0003873 (rheumatoid arthritis)
 53,068 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tumor Necrosis Factor alpha is an important mediator of immunity and inflammation, and because of its biologic activities (activation of neutrophils, release of arachidonic acid metabolites from synovial cells, induction of cartilage resorption and inhibition of proteoglycan release in cartilage) is one of the potential mediators of the chronic inflammation in rheumatoid arthritis. A commercially available ELISA was used to evaluate serum levels of Tumor Necrosis Factor alpha (TNF alpha) in patients with rheumatic diseases. We tested sera from patients with rheumatoid arthritis, seronegative arthritis, osteoarthritis, post-traumatic arthritis, systemic lupus erythematosus, progressive systemic sclerosis and normal healthy subjects as controls. Furthermore, we statistically analysed data to investigate whether a correlation exists between serum levels of TNF alpha and some humoral indexes of disease activity. The results show strikingly higher TNF alpha levels in Rheumatoid Arthritis patients when compared both to normal controls and arthritis or connective tissue disease controls. TNF alpha was also found to correlate positively with levels of the rheumatoid factor as measured either by means of the latex agglutination test (LAT) or by nephelometry. These results support the suggestion that TNF alpha plays a central role in the pathogenesis of rheumatoid arthritis.
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PMID:Circulating tumor necrosis factor alpha in rheumatoid arthritis. 832 89

In this article, the topics on TNF and TNF receptors presented in the 4th International Conference on Tumor Necrosis Factor and Related Cytokines (Netherlands, May, 1992) are briefly summarized in Japanese, based on Dr. Benjamin Bonavida's report (Cancer Update, supplement 8, 1992) with permission. Following categorized themes were discussed in the meeting: 1) regulation of TNF synthesis, especially at the transcriptional level, 2) TNF receptors, including type I (55 kd), type II (75 kd) and soluble forms, 3) TNF cytotoxicity and immunomodulation with considerations for mechanisms, 4) TNF and infectious diseases such as Plasmodium falciparum infection, 5) TNF and inflammatory diseases such as rheumatoid arthritis and 6) TNF and cancer, in attempts to overcome drug resistance and TNF toxicity.
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PMID:[TNF and TNF receptors: structure, mechanism of action, role in disease and therapy]. 839 84

Tumor necrosis factor-alpha (TNF-alpha) is a mediator of severe inflammatory processes, including rheumatoid arthritis. Suppression of TNF with a soluble type I or type II receptor molecule (TNF-RI or TNF-RII) has the potential to decrease cytokine levels and modulate inflammatory diseases in humans. However, it has recently been reported that treatment of mice with a TNF-RI:Fc immunoadhesin protein augmented Gram positive infections and subsequent mortality. To determine if TNF-alpha blockade with soluble TNF-alpha receptors might alter immune system function, assays were assessed in rodents treated with a dimeric form of the p55 TNF-RI, Tumor Necrosis Factor-binding protein (TNFbp). Administration of TNFbp resulted in suppression of primary and secondary IgG antibody responses and cell-mediated immune function. No treatment-related differences were detected in immune-enhancing assays or non-specific immune function parameters. Bacterial host resistance assays with Listeria monocytogenes, Staphylococcus aureus or Escherichia coli showed an increase in tissue colony counts only with L. monocytogenes challenged animals following TNFbp administration. These results suggest that TNFbp has the capacity to inhibit adaptive immune function in experimental animal models. Studies suggest that while reducing TNF-alpha is important in controlling cytokine-dependent disease states, maintenance of a threshold level may be critical for normal immune function.
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PMID:TNF-alpha blockade by a dimeric TNF type I receptor molecule selectively inhibits adaptive immune responses. 1110 78

Cytokine unbalance is responsible for the pathogenesis of diverse inflammatory, autoimmune and infectious diseases, and Tumor Necrosis Factor Alpha (TNF alpha), among other cytokines, plays a central role. TNF alpha production can be regulated at the transcriptional, post-transcriptional, and translational levels. Variability in the promoter and coding regions of the TNF alpha gene may modulate the magnitude of its secretory response. Up to date, several single nucleotide polymorphisms (SNPs) have been identified in the human TNF alpha gene promoter. One of these, is a guanine to adenine transition at position -308, that generates the TNF1 and TNF2 alleles, respectively. The TNF2 allele is associated to a high in vitro TNF expression, and it has also been linked to an increased susceptibility and severity, for a variety of illnesses, such as rheumatoid arthritis, systemic lupus erythematosus, inflammatory bowel disease, Alzheimer disease and cerebral malaria among others. It is also associated with a higher septic shock susceptibility and mortality. The investigation of polymorphisms within the TNF alpha cluster will be important in understanding the role of TNF alpha regulation in specific diseases.
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PMID:[Tumor necrosis factor alpha genetic polymorphism as a risk factor in disease]. 1243 54

Tumor Necrosis Factor alpha (TNF) as proinflammatory cytokine plays in the pathogenesis of many diseases an important role. In psoriasis and in psoriatic arthritis TNF is up-regulated in the skin lesion and in the synovitis. Recent trials showed that the blockade of TNF with the chimeric antibody infliximab is able to improve both, the skin lesions and the synovitis of the joints. In psoriasis in 82% of patients treated with infliximab achieved an over 75% response in the PASI index. In Psoriatic arthritis the skin improvement was correlating with the reduction of synovitis and in a small MRI controlled study all patients achieved an ACR 20 response within 10 weeks. Patients with psoriatic arthritis, who have been included in spondylarthopathy trials showed similar improvement rates. In all trials unexpected safety problems have not been reported, but the trials have been small in population and short in duration. Infliximab was used between 5 and 10 mg/kg at week 0, 2, 6 and every 8 week. It some trials the retreatment periods varied. In contrast to the treatment of rheumatoid arthritis with infliximab methotrexate was not always used as comedication. In some cases infliximab has been used in combination with other DMARDs but no trial did evaluate the combination treatment vs. the monotherapy.
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PMID:Infliximab for psoriasis and psoriatic arthritis. 1246 61

The management of rheumatoid arthritis (RA) has changed considerably during the past 15 years. Current strategies emphasize the need for early diagnosis and therapeutic intervention based on the use of disease modifying antirheumatic drugs (DMARDs). More than a dozen drugs or drug classes of DMARDs are currently in common use in RA. After a long hiatus, drug development for RA resumed a few years ago with the introduction of Leflunomide and the biologic agents. Unlike the older DMARDs (apart from the cytotoxics) the newer drugs were designed with strict reference to RA pathophysiology and the intended action of these agents is highly likely the explanation for the observed efficacy. Proinflammatory cytokines, such as interleukin-1 (IL-1) and Tumor Necrosis Factor (TNF), play an important role in maintaining the chronicity of RA and mediating tissue damage. TNF antagonists have rapidly emerged as a valuable class of antirheumatic agents. Etanercept, a dimerized version of the soluble TNF receptor II, and infliximab, a chimeric anti-TNF monoclonal antibody, are currently approved in our country for the treatment of refractory RA in the frame of ANTARES Project. Other two biologic agents, adalimumab, a fully humanized anti-TNF monoclonal antibody, and anakinra, a recombinant human IL-1 receptor antagonist, will be also soon available. It is recommended to initiate pharmacological treatment with an effective DMARD early in the course of the disease. Biological therapies have the potential to revolutionize the treatment of RA; however the use of TNF blocking agents as the first DMARD for the treatment of RA should, at present, be limited, because these compounds are expensive and one needs to include cost considerations along with those of efficacy, effectiveness and long-term safety.
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PMID:[New drugs and treatment strategies for rheumatoid arthritis]. 1294 98

Rheumatoid arthritis and Crohn's disease are costly diseases that result in significant long-term patient disability. They are chronic inflammatory diseases that are associated with increased production of Tumor Necrosis Factor (TNF). Blockage of this cytokine with bio-engineered compounds has significantly changed therapy of these diseases and has ushered in the era of biological therapy. The pro-inflammatory role of TNF is mediated by its essential respiratory burst function that is effectively inhibited by anti-TNF therapy. Anti-TNF therapy is effective in approximately two-thirds of patients to whom it is administered, but the effect is temporary. Lack of response to anti-TNF therapy stems from interplay of host-factors including: host cytokine response, disease phenotype, and antibody response to the anti-TNF agents. NOD 2, a defect present in approximately 50% of Crohn's disease patients, bears no relationship to non-response. Additionally, TNF promoter gene polymorphisms and TNF receptor gene heterogeneity play a significant role in non-response and disease course/severity. Adverse effects of anti-TNF therapy include early and delayed hypersensitivity reactions, cell-mediated infections, lupus-like syndrome, demyelinating diseases, and exacerbation of CHF.
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PMID:The biology of TNF blockade. 1455 Aug 76

Rheumatoid Arthritis (RA) is a systemic autoimmune disease that primarily manifests as a chronic symmetric polyarthritis. Treatment in the past was aimed at symptomatic pain relief. The initiation of disease modifying anti-rheumatic drugs (DMARDs) was historically started only after significant disease activity was present in order to reduce side effects from drug toxicities. Unfortunately, irreversible joint damage may occur early in the disease course. Evidence of bony destruction is common on radiographs within the first 2 years after disease onset. Therefore, more aggressive treatment became the standard with earlier introduction of DMARDs in hopes of preventing joint destruction. Within the past few years, greater understanding of the pathophysiology of RA has permitted development of therapies targeted at specific cytokines. Tumor Necrosis Factor-alpha (TNF-alpha) is a pro-inflammatory cytokine believed to play a key role in the inflammatory response in RA. Three drugs--etanercept, infliximab, and adalimumab--are anti-TNF-alpha agents approved in the United States for the treatment of RA. This article is a review of indications, clinical trials, and toxicities of these 3 agents.
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PMID:A new era in rheumatoid arthritis treatment. 1471 Oct 21

The two major advances over the 1990s in the treatment of rheumatoid arthritis (RA) were a shift in strategy from a "pyramid", in which disease modifying anti-rheumatic drugs (DMARDs) were deferred for several years, to the early aggressive use of DMARDs and widespread acceptance of methotrexate as the DMARD with the most long-term effectiveness and safety. Methotrexate courses are continued far longer than those of any other DMARD, an excellent indicator of greater effectiveness and safety. In one recent series, methotrexate was the first DMARD used in more than 80% of patients with RA. Studies which document the superiority of combinations of methotrexate with biological agents to methotrexate monotherapy select for only a minority of contemporary patients with RA who have severe disease activity and incomplete responses to methotrexate. In one locale, only 5% of patients met criteria for the Anti-Tumor Necrosis Factor Trial in RA with Concomitant Therapy (ATTRACT) trial and only 30% met the criteria for the Early Rheumatoid Arthritis (ERA) trial. In studies comparing methotrexate directly with biological agents, the biological agents have greater efficacy in patients with very severe disease, but the best results are seen in patients who take a combination of methotrexate and biologic agents. These data establish that methotrexate is the anchor drug and probably should be the first DMARD used in the majority of patients with RA at this time.
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PMID:Methotrexate as the "anchor drug" for the treatment of early rheumatoid arthritis. 1496 73

Patient registries provide valuable contributions to the field of rheumatology for both quality control and scientific purposes. With respect to the latter, patient registries are among the most important datasets used for longitudinal observational studies in rheumatic diseases, which are in turn an essential complement to data obtained from randomized, controlled trials. In Sweden a number of registries are available for such studies, ranging from general medical registries such as the in-patient registry, to rheumatoid arthritis (RA)-specific inception cohorts and biologics registries focusing on a specific patient population defined by a group of treatments. In recent years it has become particularly clear that questions regarding new therapies, their use in practice and their long-term safety, as well as aspects such as pharmacoeconomics, cannot fully be assessed using the data from clinical trials, and that registries are indispensible to obtain accurate answers to such questions. In this review we describe the Swedish rheumatology registries, including the Swedish RA registry and the Swedish biologics registries ARTIS (Antirheumatic Therapies Iin Sweden), SSATG (Southern Sweden Antirheumatic Therapy Group), and STURE (Stockholm Tumor Necrosis Factor-a Follow-up Registry). Data obtained from analyses based on these registries are reviewed. It is concluded that rheumatology registries are excellent tools for improving our knowledge base regarding rheumatic diseases.
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PMID:Rheumatoid arthritis registries in Sweden. 1627 7


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