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)

Etanercept (Enbrel, Wyeth Pharmaceuticals) is a fusion protein composed of a soluble TNF alpha receptor issued from bio-technology. It is a member of TNF alpha's family with two others marked infliximab (Remicade, Scheringh Plough Laboratory), chimeric monoclonal antibody (25 p. 100 mouse) and adalimumab (Humira, Abbott France Laboratory), humanized monoclonal antibody (100 p. 100 human). In United States, etanercept is approved by Food and Drug Administration, since 1998, to treat rheumatoid arthritis showing an inadequate response to prior therapy with other disease-modifying antirheumatic drugs (DMARDS). In France, the MA (Marketing Authorization) is more recent, in 2000, etanercept to treat active rheumatoid arthritis who showed an inadequate response to others DMARDS (like methotrexate for example), with opportunity, in 2002, to administer etanercept in active, severe RA, in first line treatment without previous use of methotrexate. Others MA have been obtained in ankylosing spondylitis (2004) polyarticular-course juvenile rheumatoid arthritis (2000), and in the treatment of psoriasic arthritis (2002). Request of MA have been realised to treat cutaneous mild to severe psoriasis in adult, which failed to respond, contradication or no tolerance with systemic treatment as methotrexate, cyclosporine or phototherapy. Among the others anti-TNF therapy, only infliximab can be prescribed, in dermatology, to treat psoriatic arthritis in France. Encouraging good results were the subject of cases report, but lacking clinical trial, predicting probably administration of etanercept in others indications in future. TNF alpha is a proinflammatory cytokine and plays an important role in the physiopathology of large inflammatory diseases. Logically, in future, we should increased prescription of biotherapy, particularly anti-TNF alpha. We have to mind short or mild-term adverse events, widely described in the literature, but long-term side effects remained unknown. Moreover, these biotherapic agents have a high cost and should be estimate.
 ...
PMID:[Etanercept]. 1632 16

Inflammatory arthropathies such as rheumatoid arthritis, ankylosing spondylitis, and psoriatic arthritis are extremely common in the community, with a prevalence of up to 5%, and they cause substantial morbidity. The development of anti-TNF agents for use initially in rheumatoid arthritis, and subsequently more broadly in inflammatory arthritis, represents the biggest advance in management of these conditions since the introduction of corticosteroid agents, and is a major vindication of public funded arthritis research. However, there are limitations of even these highly effective agents. A significant minority of patients with inflammatory arthritis do not respond to these anti-TNF agents, they are associated with substantial risk of toxicity, require parenteral administration, and are extremely expensive. New antibody treatments in development can be divided into anti-cytokine agents, cell-targeted therapies, co-stimulation inhibitors, and treatments aimed at preventing joint erosion consequent on inflammation. This review discusses the state of the art in the development of these agents for management of this common group of diseases.
 ...
PMID:Antibody treatments of inflammatory arthritis. 1637 97

Blockade of tumor necrosis factor with monoclonal antibodies, has emerged as one of the most promising therapies in some autoimmune conditions as rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis and Crohn s disease. They have shown effectiveness on reducing symptoms and modifying the progression of the disease. However, they disrupt the balance of inflammatory and immune responses and some risks associated with TNF-blockers have become apparent. The purpose of this article is to review the evidence about benefits and risk associated with the use of TNF-blockers in approved indications and to provide practical recommendations for its use in the management of these conditions.
 ...
PMID:[Tumor necrosis factor blocking agents: a review. Part I: Clinical efficacy evaluation]. 1654 22

To date, hepatotoxicity with anti-TNF therapy has been associated with concomitant liver-toxicity drugs, infection or malignant diseases. We report the case of one patient with spondyloarthropathty who presented severe liver dysfunction related to infliximab. After the second infusion serum controls showed an slightly increase of transaminases. Before the administration of fifth infusion, infliximab therapy was stopped due to severe liver damage (AST 327 mU/ml, ALT 656 mU/mL, GGT 140 mU/mL, alkaline phosphate 227 mU/mL). Ten weeks after infliximab discontinuation serum concentrations of liver blood tests were normal but ankylosing spondylitis symptoms had relapsed. Therefore, he was treated with etanercept with a rapid and sustained improvement. Serum concentrations of albumin, AST, ALT, GGT and alkaline phosphate were followed and did not change for five months.
 ...
PMID:Successful treatment with etanercept in a patient with hepatotoxicity closely related to infliximab. 1655 Mar 1

Blockade of tumor necrosis factor with monoclonal antibodies, has emerged as one of the most promising therapies in some autoimmune conditions as rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis and Crohn's disease. They have shown effectiveness on reducing symptoms and modifying the progression of the disease. However, they disrupt the balance of inflammatory and immune responses and some risks associated with TNF-blockers have become apparent. The purpose of this article is to review the evidence about benefits and risk associated with the use of TNF-blockers in approved indications and to provide practical recommendations for its use in the management of this conditions.
 ...
PMID:[Tumor necrosis factor blocking agents: a review. Part II: safety and recommendations]. 1656 59

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis is the most common cause of rapidly progressive glomerulonephritis and immune-mediated pulmonary renal syndrome. Now that the acute manifestations of the disease generally can be controlled with immunosuppressive drugs, ANCA-associated vasculitis has become a chronic and relapsing inflammatory disorder. The need to develop safer and more effective treatment has led to great interest in the mediators of chronic inflammation. There are many lessons to be learned from studies of other chronic inflammatory diseases, particularly rheumatoid arthritis (RA). The identification of a TNF-alpha-dependent cytokine cascade in the in vitro cultures of synovium in joints of patients with RA led to studies of TNF blockade in experimental models of arthritis and subsequently to clinical trials. These have culminated in the widespread introduction of anti-TNF therapy not only in RA but also in Crohn disease, ankylosing spondylitis, and several other chronic inflammatory disorders. Following a similar investigative pathway, studies that show the importance of TNF production by leukocytes and intrinsic renal cells in glomerulonephritis have been followed by the demonstration of the effectiveness of TNF blockade in several experimental models of glomerulonephritis and vasculitis. In experimental autoimmune vasculitis, improvement in disease was paralleled by a reduction in leukocyte transmigration, as demonstrated by intravital microscopy. The benefit of infliximab (a mAb to TNF) in ANCA-associated vasculitis was recently reported in a prospective open-label study. However, the use of etanercept (a soluble TNF receptor fusion protein) was not found to be of significant benefit in a randomized, controlled trial in patients with Wegener granulomatosis. Therefore, there is a need for further evaluation of the use of anti-TNF antibodies in patients with ANCA-associated glomerulonephritis.
 ...
PMID:Is there a role for TNF-alpha in anti-neutrophil cytoplasmic antibody-associated vasculitis? Lessons from other chronic inflammatory diseases. 1662 28

CXC chemokines are potent attractants of neutrophil granulocytes, T cells or natural killer cells. Toll-like receptors (TLR) recognize microbial components and are also activated by endogenous molecules possibly implicated in autoimmune arthritis. In contrast to CXC chemokine ligand 8 (CXCL8), no CXC chemokine receptor 3 (CXCR3) ligand (ie CXCL9, CXCL10 and CXCL11) was induced by bacterial TLR ligands in human microvascular endothelial cells (HMVEC). However, peptidoglycan (PGN), double-stranded (ds) RNA or lipopolysaccharide (LPS) (TLR2, TLR3 or TLR4 ligands, respectively) synergized with interferon-gamma (IFN-gamma) at inducing CXCL9 and CXCL10. In contrast, enhanced CXCL11 secretion was only obtained when IFN-gamma was combined with TLR3 ligand. Furthermore, flagellin, loxoribine and unmethylated CpG oligonucleotide (TLR5, TLR7 and TLR9 ligands, respectively) did not enhance IFN-gamma-dependent CXCR3 ligand production in HMVEC. In analogy with TLR ligands, tumor necrosis factor-alpha (TNF-alpha) or interleukin-1beta (IL-1beta), in combination with IFN-gamma, synergistically induced CXCL9 and CXCL11 in HMVEC and human fibroblasts, two fundamental cell types delineating the joint cavity. Etanercept, a humanized soluble recombinant p75 TNF-receptor/IgG(1)Fc fusionprotein, neutralized synergistic CXCL9 production induced by TNF-alpha plus IFN-gamma, but not synergy between IFN-gamma and the TLR ligands PGN or LPS. Synovial chemokine concentrations exemplify the physiopathological relevance of the observed in vitro chemokine production patterns. In synovial fluids of patients with spondylarthropathies (ie ankylosing spondylitis or psoriatic arthritis) or rheumatoid arthritis, significantly enhanced CXCL9, but not CXCL11 levels, were detected compared to concentrations in synovial fluids of patients with metabolic crystal-induced arthritis. Thus, CXCL9 is an important chemokine in autoimmune arthritis.
 ...
PMID:TLR ligands and cytokines induce CXCR3 ligands in endothelial cells: enhanced CXCL9 in autoimmune arthritis. 1684 31

Chronic infections, such as hepatitis C, in the setting of rheumatic disorders pose a potential hindrance to optimal management because of possible complications linked to the institution of immune suppression, as well as the high incidence of hepatotoxicity associated with many of the disease-modifying antirheumatic drugs included in the conventional therapeutic regimens. In the setting of hepatitis C, however, the effect of TNFalpha blockade may be potentially beneficial because TNFalpha appears to be involved in the pathogenesis of liver fibrosis through the stimulation of apoptotic pathways. Data related to this subject are, unfortunately, still limited and without detailed information regarding the clinical progression of the rheumatic disorder. We report the cases of two patients, one with ankylosing spondylitis and one with psoriatic arthritis, who were efficiently treated long-term with anti-TNF agents for their rheumatic disease without any evidence of reactivation or flaring of their hepatitis C infection or deterioration of their liver function. Our results indicate that TNFalpha blockade is a highly efficient and uncompromising therapy in hepatitis C-affected individuals with connective tissue disorders. However, systematic, large-scale studies addressing the issue of safety of these new efficient drugs, i.e., monoclonal antibodies targeted against TNFalpha, in patients with chronic hepatitis C will be needed to properly assess the risks and benefits of this treatment in analogous cases.
 ...
PMID:Inhibition of TNFalpha does not induce viral reactivation in patients with chronic hepatitis C infection: two cases. 1700 55

Ankylosing spondylitis (AS) is a chronic, immunologically mediated rheumatic disease whose progression largely depends on the extent of inflammatory activity. In contrast to rheumatoid arthritis (RA), therapeutic control of AS is very limited. Therapy of ankylosing spondylitis should not only control inflammatory processes, but also prevent structural damages and maintain the functions. Until recently, physiotherapy and non-steroidal antiphlogistics (NSA) therapy was a gold standard of AS treatment. NSA therapy alleviates inflammatory pain of spine in 60 to 80% of patients. According to the most recent findings, long-term administration of NSA can affect also X-ray progression. DMARD therapy, which is efficient in RA, has insignificant effect on axial form of AS. Sulfasalazine proved to be efficacious against peripheral form of AS; administration of MTX and leflunomide is not supported by controlled studies. Peripheral arthritis and enthesitis is usually treated by short-term application of corticoids. The fact remains that an important role in AS immunopathogenesis is played by TNF alpha whose increased levels were found in patients with AS in serum, synovial fluid and SI joints. Anti-TNF therapy with infliximab and etanercept proved to be highly efficacious in patients with AS resistant to conventional therapy. Infliximab and etanercept reduced the disease activity (50% improvement in more than half of patients), improved the function and slowed down the structural damage. MRI studies of anti-TNF therapy proved reduction of inflammatory activity in SI joints and spine. Other studies verified the efficacy of adalimumab in AS therapy and showed that adalimumab is a promising drug. Also, several randomized clinical studies proved efficacy of thalidomide whose administration, however, is limited by its severe adverse effects. Until now, the results of studies focused on pamidronate therapy appear to be rather controversial. Better understanding of AS pathogenesis led to implementation of new therapeutic procedures that significantly improve activity and functional condition of patients.
 ...
PMID:[Ankylosing spondylitis--the current situation and new therapeutic options]. 1696 16

In addition to the typical clinical symptoms, conventional x-rays and magnetic resonance imaging (MRI) are important for the diagnosis and management of ankylosing spondylitis (AS). While radiography is mainly useful for detecting chronic structural changes, MRI is, in addition, able to detect active inflammation. The detection of structural changes in the sacroiliac joints and, in part, the spine, remains the gold standard for the diagnosis of AS. The detection of active sacroiliitis or spondylitis in early disease stages is only possible using MR techniques such as STIR and T1 post-gadolinium sequences. Lateral radiographs of the spine are useful for detecting shiny corners and the characteristic syndesmophytes and ankylosis. The modified Stoke Anklyosing Spondylitis Spine Score (SASSS) is the best scoring method for quantifying such changes, allthough only the cervical and the lumber spine are evaluated with this method. MRI changes can also be quantified. New scoring methods are sensitive to change only 3 months after initiation of therapy with anti-TNF agents.
 ...
PMID:[Imaging in ankylosing spondylitis]. 1702 59


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>