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

Etanercept, a soluble recombinant human tumor necrosis factor receptor (TNFr), is effective and well tolerated in the treatment of rheumatoid arthritis, juvenile rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, and psoriasis. The primary objective of this study was to investigate the potential pharmacokinetic and pharmacodynamic interaction between digoxin and etanercept at steady state. In a crossover, open-label, nonrandomized, 3-period study, 12 healthy male subjects received loading oral doses of digoxin 0.5 mg every 12 hours on day 1 and 0.25 mg every 12 hours on day 2, followed by a daily maintenance dose of 0.25 mg for a total of 27 days. Etanercept was administered as a twice-weekly 25-mg subcutaneous dose beginning on day 9 and continuing up to day 37 for a total of 9 doses. All ratios of maximum plasma concentration (C(max)) and area under the plasma concentration versus time curve (AUC) for pharmacokinetics of digoxin fell within the confidence interval of 0.8 to 1.25. Although not considered clinically relevant, the mean C(max) and AUC of etanercept were 4.2% and 12.5% lower, respectively, when etanercept was given with digoxin than when administered alone. There were no clinically relevant changes in the electrocardiogram (ECG) parameters, and adverse events did not increase when both drugs were combined. In conclusion, there is no clinically relevant interaction between etanercept and digoxin, and both drugs can be safely coadministered without the need for a dosage adjustment.
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PMID:Absence of a clinically relevant interaction between etanercept and digoxin. 1549 42

Etanercept is a dimeric fusion protein that has been approved for the treatment of rheumatoid arthritis, juvenile rheumatoid arthritis, psoriatic arthritis, active ankylosing spondylitis and moderate to severe plaque psoriasis. It has been reported to be useful in other variants of psoriasis, Still's disease, recurrent aphthous ulcers, and a variety of rare cutaneous conditions. Its cutaneous side effects are rare and include injection site reactions, cutaneous lupus, and cutaneous vasculitis. Its systemic side effects are also rare and include induction or worsening of infections, lupus, multiple sclerosis, and congestive heart failure. Linkage to an increased risk of lymphoma is unclear. In short, etanercept is a promising medication with substantial benefits and use will probably increase in the future. This review surveys off-label uses and side effects of etanercept.
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PMID:The medical uses and side effects of etanercept with a focus on cutaneous disease. 1562 48

Etanercept is a tumor necrosis factor antagonist with anti-inflammatory effects. It is currently approved in the US for psoriasis, psoriatic arthritis, ankylosing spondylitis, rheumatoid arthritis and juvenile rheumatoid arthritis. Clinical trials have shown this agent to have an excellent safety profile and to be well tolerated by both adult and pediatric patients.
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PMID:Etanercept (Enbrel) -- an update. 1565 32

As psoriasis and psoriatic arthritis are chronic in nature, ideal treatment should have sustained efficacy, with minimal short- and long-term toxicities to allow lifelong treatment. Traditional therapies used for psoriatic arthritis or psoriasis, including phototherapies and systemic agents, do not satisfy these criteria. Ninety percent of patients surveyed in 1998 by The National Psoriasis Foundation were not satisfied with their treatment options. Several observations have supported the introduction of the tumor necrosis factor (TNF) antagonist etanercept as a treatment for psoriatic disease, including the failure of traditional therapies to meet patient needs, evidence that TNF plays a fundamental role in the inflammatory processes underlying psoriatic arthritis and psoriasis, and the safety and efficacy of this agent in other inflammatory, immune-mediated diseases, such as rheumatoid arthritis (RA). Etanercept prevents initiation of the proinflammatory cascade by competitively binding TNF. First indicated for RA, etanercept is also approved for the treatment of psoriatic arthritis, juvenile RA, ankylosing spondylitis, and most recently psoriasis. Etanercept provides dermatologists with a safe, effective, and convenient treatment option for patients with psoriatic arthritis and psoriasis, which can be used continuously with or without traditional therapies. The self-administered injections provide a distinct advantage over traditional therapies that often require frequent office visits and laboratory monitoring, and other biologic agents that require administration in the doctor's office. Dermatologists should be aware of the ongoing research with etanercept in psoriasis and other dermatologic conditions.
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PMID:Use of etanercept in the dermatology setting. A review. 1567 90

Tumour necrosis factor-alpha (TNF-alpha) is one of the inflammatory cytokines. It is released by activated monocytes, macrophages and T lymphocytes and promotes inflammation. TNF-alpha binds to two receptors; one of these is the type 2 TNF receptor (p75). Etanercept is a soluble TNF-receptor fusion protein. It consists of two linked dimmers, each with a ligand-binding portion of the higher affinity type 2 TNF receptor (p75). This fusion protein binds to TNF-alpha and prevents it from interacting with its receptor. Etanercept is given by subcutaneous administration at a dose of 25 mg twice a week. This dosing reflects its half-life of about 4 days. Clinical trials show etanercept is effective and safe to use in rheumatoid arthritis (RA). It reduces disease activity and limits progressive joint damage in both early and late disease. It can be used as a monotherapy or in combination with methotrexate, and in this, the latter approach appears most effective. It is also effective in psoriatic arthritis and ankylosing spondylitis. Although the biologic appears safe, caution is needed to ensure it does not re-activate tuberculosis. It should not be used in patients with disseminated sclerosis, and there are concerns about a potential relationship to lymphoma. Its high cost means there will be continuing debate about the ideal position of this new biologic within the treatment pathway of RA. At present, it is recommended for use when methotrexate and another disease-modifying drug have failed.
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PMID:Etanercept in arthritis. 1570 75

Blockade of tumor necrosis factor (TNF) has emerged as one of the most promising therapies in rheumatoid arthritis (RA). Three agents are currently available as specific TNF antagonists, etanercept (Enbrel), infliximab (Remicade), and adalimumab (Humira). Data from noncomparative trials suggest that all 3 agents have comparable therapeutic activity in RA. Etanercept and infliximab have also demonstrated beneficial activity in other inflammatory arthritides [i.e., psoriatic arthritis and ankylosing spondylitis (both agents) and juvenile rheumatoid arthritis (etanercept only)] and inflammatory diseases (i.e., psoriasis and uveitis). Their effects in granulomatous diseases are more variable, with only infliximab demonstrating clear efficacy in the treatment of Crohn's disease, sarcoidosis, and Wegener's vasculitis. In this brief review current efficacy data are summarized and possible explanations for observed clinical differences are explored.
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PMID:Differentiating the efficacy of tumor necrosis factor inhibitors. 1574 57

Up to 2 in 1,000 adults in the UK have ankylosing spondylitis. This chronic inflammatory disease causes pain and stiffness in the spine and sacroiliac and peripheral joints, and may also affect the eyes, heart and ungs. Characteristic features include ankylosis of the spine with a progressive loss of spinal mobility. Treatment with NSAIDs and physical therapy can provide symptomatic relief of pain and stiffness, but does not modify the course of the disease (e.g. slow or prevent ankylosis). In general, disease-modifying antirheumatic drugs (DMARDs), such as gold, methotrexate and sulfasalazine, have little or no effect in ankylosing spondylitis. [symbol: see text]Etanercept (Enbrel--Wyeth) and [symbol: see text]infliximab (Remicade--Schering-Plough), two drugs which block the inflammatory effect of tumour necrosis factor (TNF), are now licensed for the treatment of patients with severe ankylosing spondylitis whose symptoms have not responded adequately to conventional therapy. Here we review the place of these TNF antagonists in the management of such individuals.
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PMID:TNF antagonists for ankylosing spondylitis. 1576 84

Etanercept, a fully humanized soluble recombinant tumor necrosis factor receptor fusion protein, is an approved treatment for rheumatoid arthritis, juvenile rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, and psoriasis. Etanercept is absorbed slowly from the site of subcutaneous injection, with time to peak concentration at approximately 48 to 60 hours, and is cleared slowly from the body with a t(1/2) of 70 to 100 hours. The absolute bioavailability of etanercept was 58% in healthy subjects following subcutaneous administration. The 25-mg twice-weekly dosage regimen generates systemic exposures comparable to 50 mg once weekly, as predicted by pharmacokinetic modeling and simulation and later confirmed by clinical studies. The pharmacokinetics of etanercept in patients with rheumatoid arthritis are comparable to those in healthy individuals and patients with ankylosing spondylitis, congestive heart failure, and psoriasis. In children with polyarticular-course juvenile rheumatoid arthritis, after subcutaneous doses of 0.4 mg/kg twice weekly, the clearance of etanercept may be slightly reduced in children aged 4 to 8 years. Pharmacokinetic simulation predicts that a dose of 0.8 mg/kg once weekly generates comparable systemic exposure as 0.4 mg/kg twice weekly. No requirement for etanercept dosage adjustment is needed when etanercept is coadministered with warfarin, digoxin, or methotrexate.
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PMID:Clinical pharmacokinetics of etanercept: a fully humanized soluble recombinant tumor necrosis factor receptor fusion protein. 1583 71

The tumor necrosis factor inhibitors are a diverse group of biologic agents. Although there are no studies that directly compare these agents, data from noncomparative trials suggest that all 3 agents have therapeutic activity in rheumatoid arthritis. Etanercept and infliximab have also demonstrated beneficial activity in other inflammatory arthritides (ie, psoriatic arthritis and ankylosing spondylitis [both agents] and juvenile rheumatoid arthritis [etanercept only]) and inflammatory diseases (ie, psoriasis and uveitis). Their effects in granulomatous diseases are more variable, with only infliximab demonstrating clear efficacy in the treatment of Crohn's disease, sarcoidosis, and Wegener's granulomatosis. The purpose of this brief review is to summarize current efficacy data and explore possible explanations for observed clinical differences.
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PMID:Differentiating the efficacy of the tumor necrosis factor inhibitors. 1585 48

Juvenile idiopathic arthritis is group of diseases of unknown aetiology characterised by the occurrence of chronic arthritis during childhood. Compared to adult onset rheumatoid arthritis, its course is more variable. Increasing knowledge of the inflammatory process as well as in molecular genetics and biotechnology has enable the production of new drugs, the biologicals. These are able to specifically block mechanisms of immune activation and thereby interfere with the inflammatory process. An increasing number of biologicals have been tried in clinical studies in adults suffering from rheumatoid arthritis, psoriasis or psoriasis arthritis and a couple of them were already licensed for treatment. Treatment of juvenile idiopathic arthritis by blockade of tumournecrosis-factor (TNF) using the soluble receptor Etanercept or the monoclonal antibodies Infliximab and Adalimumab showed comparable clinical efficacy. Blockade of TNF therefore already reached a certain place in the therapeutic algorythm for treatment of juvenile idiopathic arthritis. Currently, only Etanercept is licensed for treatment of active juvenile polyarthritis refractory to methotrexate. Studies using Infliximab and Adalimumab will be completed in the near future. However, antibodies blocking TNF may already be used in patients suffering from active uncontrolled chronic uveitis in whom visual impairment is threatening. TNF blockers may also be indicated in juvenile ankylosing spondylitis. The use of further biologicals, the interleukin-1 receptor antagonist Anakinra, Atlizumab (MRA) blocking the receptor for interleukin-6 or Abatacept, an inhibitory ligand of the co-stimulatory T cell membrane molecule CD28, remain experimental and should be preserved for clinical studies.
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PMID:[Importance of the new biologicals and cytokine antagonists in the treatment of juvenile idiopathic arthritis (JIA)]. 1596 16


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