Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P01889 (ankylosing spondylitis)
 5,717 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tumor necrosis factor-alpha (TNF-alpha) plays an important role in the pathogenesis of such diseases as rheumatoid arthritis, Crohn's disease, ankylosing spondylitis, psoriatic arthritis, and juvenile chronic arthritis. Recent years have brought improvement in the understanding of the pathogeneses of these diseases, resulting in the production of new groups of biological drugs, including, among others, anti-TNF-alpha antibodies. The use of TNF inhibitors has been a great advance in the treatment of patients with these inflammatory diseases. Infliximab and adalimumab are monoclonal antibodies that bind to and neutralize the activity of TNF-alpha. Infliximab is a mouse/human chimera that joins the variable regions of a mouse antibody to the constant region of human IgG1. Adalimumab is a fully human IgG1 antibody. Etanercept is a dimeric fusion protein that joins the human p75 TNF receptor to the Fc domain of human IgG1. The beneficial effects of the anti-TNF monoclonal antibodies infliximab and adalimumab and the soluble receptor fusion protein etanercept in the treatment of rheumatoid arthritis, especially in patients resistant to other disease-modifying antirheumatic drugs (DMARDs), are discussed. We observe stoppage of articular destruction during treatment with TNF-alpha inhibitors. Soon after the introduction of this therapy it was found that these agents have a propensity for stimulating the production of autoantibodies and antibodies against themselves. In this review, recent studies analyzing the effect of TNF-alpha blockade (infliximab, etanercept, and adalimumab) on the ANA, anti-dsDNA, and anticardiolipin antibody profiles in autoimmune diseases are discussed.
 ...
PMID:[Autoimmune aspects of treatment with TNF-alpha inhibitors]. 1778 35

Tumor necrosis factor-alpha (TNFalpha) inhibition is effective in the treatment of moderate-to-severe psoriasis. We report on 120 patients from the literature including six new patients (three women and three men) who developed pustular lesions during treatment with TNFalpha inhibitors. We identified 72 women and 36 men (several papers did not specify the gender of patients) with an age range of 13-78 years (mean 42.3 years). The primary diagnoses were rheumatoid arthritis (n = 61), ankylosing spondylitis (n = 21), psoriasis (n = 10), Crohn disease (n = 8), SAPHO (synovitis acne pustulosis hyperostosis osteitis) syndrome (n = 3), psoriatic arthritis (n = 2), and other diagnoses (n = 15). Psoriasis (except palmoplantar pustular type) was the most common adverse effect during anti-TNFalpha treatment (n = 73), followed by palmoplantar pustular psoriasis (n = 37) and psoriasis of the nail (n = 6), sometimes combined in the same patient. Palmoplantar pustulosis and psoriasiform exanthema was the diagnosis in ten patients each. A positive personal history of psoriasis was recorded in 25 patients. A positive family history was noted in eight patients. No data about personal (n = 7) or family history (n = 46) were available in a number of patients. Newly induced psoriasis was diagnosed in 74 patients whereas an exacerbation or aggravation of a pre-existing psoriasis was noted in another 25 patients. All three TNFalpha inhibitors available on the market were involved: infliximab (63 patients), etanercept (37 patients), and adalimumab (26 patients). Several patients were treated with more than a single TFNalpha inhibitor. The timing of cutaneous adverse effects (psoriasis and psoriasiform rash) varied considerably among patients, ranging from after a single application to a delayed response of up to 63 months after initiation of treatment. The mean time to appearance of the cutaneous adverse effect for all TNFalpha inhibitors was 9.5 months. Cessation of the responsible TNFalpha inhibitor was carried out in 47 patients either alone or in association with adjuvant anti-psoriatic therapy (mostly topical). This resulted in complete remission in 21 patients, partial remission in 20 patients, and stable disease in another three patients; in the other three patients, the outcome was not reported. TNFalpha inhibition was continued in 47 patients but anti-psoriatic adjuvant therapy was introduced. The outcome in this group was complete remission in 22 patients, partial remission in 25 patients, and stable disease in 2 patients. The response rate (complete remission plus partial remission) was 93.2% and 95.9%, respectively, in each group. In six patients, switching from one TNFalpha inhibitor to another one immediately after cutaneous adverse effects occurred resulted in an improvement in five patients. In nine patients, a second TNFalpha inhibitor was initiated after a break in TNFalpha inhibition. The response to a second or third drug in these patients was mixed. The underlying pathomechanisms of induction of psoriasis or psoriasiform exanthemata by TNFalpha inhibitors remain elusive but there is reason to assume that induction of such adverse events has more than one pathophysiology.
 ...
PMID:Tumor necrosis factor-alpha inhibitor-induced psoriasis or psoriasiform exanthemata: first 120 cases from the literature including a series of six new patients. 1809 39

Tumor necrosis factor (TNF) has been implicated in a number of arthritic disease states, including rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis. Adalimumab is the first fully human, high-affinity, recombinant immunoglobulin G(1) (IgG(1)) anti-TNF monoclonal antibody. Adalimumab in combination with methotrexate or standard antirheumatic therapies, or as monotherapy, is effective in the treatment of adults with active rheumatoid arthritis who have had an inadequate response to disease-modifying antirheumatic drugs. Adalimumab is also effective in the treatment of patients with moderately to severely active psoriatic arthritis, improving both joint and skin manifestations of the disease as well as disability due to joint damage. In the Adalimumab Trial Evaluating Long-term Efficacy and Safety in Ankylosing Spondylitis (ATLAS), adalimumab significantly reduced the signs and symptoms of active ankylosing spondylitis and established a sustained clinical response in patients who had an inadequate response or intolerance to nonsteroidal antiinflammatory drug therapy. Overall, across these indications, adalimumab demonstrated a rapid onset of action, sustained efficacy with long-term treatment, and was well-tolerated, with few patients discontinuing treatment because of adverse events. The safety profile was similar to other TNF antagonists. Inhibition of TNF activity by adalimumab also significantly improved physical functioning and quality of life measures.
 ...
PMID:Adalimumab in the treatment of arthritis. 1836 Jun 21

Treatment of refractory sarcoidosis may be challenging for clinicians. Despite treatment with conventional therapy, sarcoidosis may be progressive and debilitating. Previous studies have implicated a role for tumor necrosis factor-alpha in granuloma formation as seen in sarcoidosis. Tumor necrosis factor-alpha inhibitors are currently approved to treat rheumatoid arthritis, Crohn disease, psoriasis, psoriatic arthritis, ankylosing spondylitis, and juvenile rheumatoid arthritis. There have been recent case-reports supporting treatment of refractory and multisystem sarcoidosis with such agents. We report a case of sarcoidosis, involving the lung and vertebrae, which was refractory to conventional therapy. Our patient's clinical symptoms and radiologic lesions of vertebral sarcoid dramatically improved after treatment with infliximab.
 ...
PMID:Refractory vertebral sarcoidosis responding to infliximab. 1876 26

Tumor necrosis factor-alpha (TNF-alpha) inhibitors such as adalimumab are increasingly used in the treatment of chronic inflammatory diseases, including rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis. In Europe, this group of drugs also has been approved for therapy of moderate to severe psoriasis recently. With increased application of adalimumab, the possible adverse effects occurring in the course of treatment steadily gained more attention. Among these, infection and localized skin eruptions are the most common. Usually, the cutaneous symptoms rapidly resolve after discontinuation of the drug. Here, however, we report on a woman with rheumatoid arthritis who developed a therapy-refractory, generalized pustular rash during treatment with adalimumab. After different unsuccessful therapeutic attempts, only a combined treatment with prednisone, methotrexate, and cyclosporinee eventually led to marked improvement. To the best of our knowledge, this is the first report on a generalized, therapy-resistant pustulosis as an adverse effect of adalimumab.
 ...
PMID:Generalized pustulosis induced by adalimumab in a patient with rheumatoid arthritis - a therapeutic challenge. 1898 81

Biomarkers may provide information that promotes understanding of prognosis, disease activity, and pathogenesis in ankylosing spondylitis. Biomarkers reflecting disease activity (metallo-proteinase-3) and inflammatory lesions on magnetic resonance imaging predict new bone formation and are ameliorated by anti-tumor necrosis factor therapy, yet this treatment may not prevent new bone formation. Moreover, elevated levels of biomarkers reflecting tissue repair (bone-specific alkaline phosphatase) post-treatment together with magnetic resonance imaging indicates such treatment may even promote repair through new bone formation. Tumor necrosis factor regulation of Dickkopf-1 may constitute a molecular brake that controls osteoblastogenesis through wingless and bone morphogenetic proteins in an established inflammatory lesion in ankylosing spondylitis.
 ...
PMID:What do biomarkers tell us about the pathogenesis of ankylosing spondylitis? 1894 53

Tumor necrosis factor-alpha (TNF-alpha) is a central regulator of inflammation, and TNF-alpha antagonists may be effective in treating inflammatory disorders in which TNF-alpha plays an important pathogenetic role. Recombinant or modified proteins are an emerging class of therapeutic agents. To date, several recombinant or modified proteins which acts as TNF antagonists have been disclosed. In particular, antibodies that bind to and neutralise TNF have been sought as a means to inhibit TNF activity. Inhibition of TNF has proven to be an effective therapy for patients with rheumatoid arthritis and other forms of inflammatory disease including psoriasis, psoriatic arthritis, and ankylosing spondylitis, inflammatory bowel disease. Additionally, the efficacy of preventing septic shock and AIDS has been questioned as a result of recent research. The currently available therapies include a soluble p75 TNF receptor:Fc construct, etanercept, a chimeric monoclonal antibody, infliximab, and a fully human monoclonal antibody, adalimumab. Certolizumab pegol is a novel TNF inhibitor which is an antigen-binding domain of a humanized TNF antibody coupled to polyethylene glycol (PEG) to increase half-life, and thus is Fc-domain-free. In this review, we discuss briefly the present understanding of TNF-alpha-mediated biology and the current therapies in clinical use, and focus on some of the new therapeutic approaches with small-molecule inhibitors. Moreover, we examine recent reports providing important insights into the understanding of efficacy of thalidomide and its analogs, as TNF-alpha activity inhibitories, especially in therapies of several inflammatory diseases within the nervous system.
 ...
PMID:TNF-alpha as a therapeutic target in inflammatory diseases, ischemia-reperfusion injury and trauma. 1968 89

Tumor necrosis factor-alpha (TNF-alpha) was first isolated two decades ago as a macrophageproduced protein that can effectively kill tumor cells. TNF-alpha is also an essential component of the immune system and is required for hematopoiesis, for protection from bacterial infection and for immune cell-mediated cytotoxicity. Extensive research, however, has revealed that TNF-alpha is one of the major players in tumor initiation, proliferation, invasion, angiogenesis and metastasis. The proinflammatory activities link TNF-alpha with a wide variety of autoimmune diseases, including psoriasis, inflammatory bowel disease, rheumatoid arthritis, systemic sclerosis, systemic lupus erythematosus, multiple sclerosis, diabetes and ankylosing spondylitis. Systemic inhibitors of TNF such as etanercept (Enbrel) (a soluble TNF receptor) and infliximab (Remicade) and adalimumab (Humira) (anti-TNF antibodies) have been approved for the treatment inflammatory bowel disease, psoriasis and rheumatoid arthritis. These drugs, however, exhibit severe side effects and are expensive. Hence orally active blockers of TNF-alpha that are safe, efficacious and inexpensive are urgently needed. Numerous products from fruits, vegetable and traditional medicinal plants have been described which can suppress TNF expression and TNF signaling but their clinical potential is yet uncertain.
 ...
PMID:Targeting TNF for Treatment of Cancer and Autoimmunity. 1976 65

The signs and symptoms of ankylosing spondylitis (AS) respond inadequately to nonsteroidal antiinflammatory drugs, corticosteroids, and disease modifying antirheumatic drugs in quite a number of patients. Tumor necrosis factor inhibitors have demonstrated to be of value in reducing AS disease activity in clinical trials. The efficacy and safety of both etanercept and infliximab in patients with ankylosing spondylitis were compared in a 2-year open label randomised study. Our results are consistent with a significant more rapid clinical improvement in the infliximab treated group. Treatment with both etanercept and infliximab at the end of the study was effective, safe, and well tolerated.
 ...
PMID:A 2-year comparative open label randomized study of efficacy and safety of etanercept and infliximab in patients with ankylosing spondylitis. 1985 72

Tumor necrosis factor-alpha (TNF-alpha), a proinflammatory cytokine, has been implicated in the pathology of a variety of chronic autoimmune diseases such as rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis. The introduction of TNF-alpha inhibitors represented a significant advance in the management of these diseases but the responses of individual patients to TNF-alpha inhibitors are not homogeneous and more therapeutic tools are needed. Golimumab (CNTO-148) is a novel anti-TNF-alpha human monoclonal antibody that blocks both soluble and transmembrane TNF-alpha. It is indicated in the treatment of adults with moderately to severely active rheumatoid arthritis in combination with methotrexate, in adults with active and progressive psoriatic arthritis either alone or in combination with methotrexate, and in adult patients with active ankylosing spondylitis who have had an inadequate response to conventional therapies. Golimumab has generally been well tolerated in clinical trials with a safety profile comparable to other currently available TNF-alpha inhibitors. Its advantages are that it can be administered s.c. once monthly, it is labeled for patient self-administration and is suitable for both s.c. and i.v. administration. Golimumab is currently being investigated in other chronic inflammatory diseases.
 ...
PMID:Golimumab: A novel anti-TNF-alpha human monoclonal antibody for rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis. 2020 Jun 92


<< Previous 1 2 3 4 5 6 Next >>