Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: KEGG:D02598 (Infliximab)
 1,133 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

CD and UC represent a spectrum of chronic IBD that present in protean ways and are accompanied by a variety of systemic sequelae. Sulfasalazine and the newer 5-aminosalicylates are important in the management of mild-to-moderate disease, whereas corticosteroids remain the primary therapy for most patients with moderate-to-severe disease (Tables 2-5). The toxicities associated with long-term steroid therapy, combined with their ineffectiveness as maintenance medications, have led to increased use of immunomodulators, such as azathioprine and 6-MP, for the treatment of steroid-dependent and steroid-resistant IBD. Infliximab is a novel therapeutic adjunct for chronically active and fistulizing CD that will herald a new era of biologic therapy for IBD. Meanwhile, CSA remains an alternative to urgent colectomy in severe UC unresponsive to corticosteroids and also for CD patients with severe disease or refractory fistulas. Finally, continued insights into the etiopathogenic pathways in IBD will provide evolving and innovative approaches until the eventual causes and cures are elucidated. In the meantime, clinicians should remain optimistic regarding current ability to reduce the morbidity and maintain the quality of life for patients suffering with these frustrating diseases.
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PMID:Medical therapy for inflammatory bowel disease. 1037 70

A groundswell of therapeutic modalities is presently sweeping through the field of inflammatory bowel disease (IBD), revolutionising the treatment and management of these disorders. At the forefront of newer agents are biological therapies, also referred to as 'biologics'. These include infliximab (cA2), CDP 571, rhIL-10, ICAM-1 antisense oligonucleotide (ISIS 2302) and opreleukin (rhIL-11). Among these, infliximab and CDP 571 are perhaps the most promising, particularly in Crohn's disease. Both are anti-TNF alpha monoclonal antibody formulations with proven efficacy at doses of 5 mg/kg for inducing remission in patients with moderate to severe refractory Crohn's disease. Infliximab is beneficial in the treatment of fistulous Crohn's disease as well. Anti-inflammatory cytokines such as rhIL-10 and opreleukin (rhIL-11) in early reports appear efficacious in Crohn's disease but not in ulcerative colitis. Budesonide, a second generation glucocorticoid, in an oral controlled ileal release capsule, is an attractive alternative to prednisone for treating active Crohn's disease of the distal ileum and proximal colon. Also available as an enema, budesonide's efficacy approximates that of prednisolone for inducing remission in active distal ulcerative colitis. Postoperative recurrences of Crohn's disease are a common clinical scenario. Recently, mesalazine, metronidazole and mercaptopurine have been re-evaluated in the postoperative setting. In the largest postoperative prophylaxis trial, mercaptopurine was superior to both placebo and mesalazine in preventing clinical, endoscopic and radiographic relapses. Finally, miscellaneous therapies such as transdermal nicotine, nicotine tartrate enemas and topical lidocaine used in pilot studies for ulcerative colitis have shown promise. Case reports of thalidomide and tacrolimus (FK 506) have reported beneficial effects in treating complicated, refractory Crohn's disease.
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PMID:Promising new agents for the treatment of inflammatory bowel disorders. 1056 35

The medical treatment of inflammatory bowel disease is dependent on disease activity and bowel involvement. Severe Crohn's disease and ulcerative colitis are primarily treated with corticosteroids. Alternatively, if inflammation is localised in the right colon and ileum, budesonide may be used in view of its low systemic side effects. In distal colitis and perianal disease, topical therapy with steroids is very effective. In moderate disease preparations containing 5-aminosalicylate (5-ASA) may be used. The latter are highly effective applied locally in distal disease. Steroids should be tapered down and whenever possible not used to maintain remission. In patients with ulcerative colitis, 5-ASA is effective in maintaining remission, whereas this medication plays only a limited role in Crohn's disease. Refractory disease or patients with multiple flare-ups should be treated with azathioprine. Infliximab, an anti-TNF-alpha antibody, is a potent therapy for fistulising Crohn's disease or steroid-refractory disease. Other approved and experimental treatments are discussed.
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PMID:[Drug treatment of chronic inflammatory bowel diseases: current status and prospects]. 1071 13

We treated a 57-year-old woman for refractory inflammatory bowel disease with a humanized anti-tumor necrosis factor alpha monoclonal antibody (Infliximab). The patient also had a 15-year history of Crohn's disease and a 20-year history of moderate to severe psoriasis. She received a single infusion of Infliximab (5 mg/kg). Two weeks after the infusion her psoriasis had dramatically improved in appearance. To our knowledge, our case is the first reported instance of successful anti-tumor necrosis factor alpha therapy in psoriasis.
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PMID:Treatment with anti-tumor necrosis factor alpha (TNF-alpha) monoclonal antibody dramatically decreases the clinical activity of psoriasis lesions. 1077 63

Traditional treatment approaches for patients with inflammatory bowel disease involve 1) pharmacologic management with aminosalicylates, corticosteroids, immunomodulatory agents, and antibiotics; and 2) nonpharmacologic management by surgical and dietary means. Complications and inadequate responses to current treatment modalities have resulted in the development of new and more specific biologic therapies. The proinflammatory cytokine tumor necrosis factor alpha (TNF alpha) is present in elevated concentrations in patients with inflammatory bowel disease; therefore, it has been targeted for treatment approaches. Infliximab is a chimeric, monoclonal antibody to TNF alpha developed to inhibit the interaction of TNF alpha with its receptor, to result in amelioration of inflammation. This biologic agent has received the most attention and is the most studied of those for the treatment of patients with Crohn's disease. This article reviews the symptoms of inflammatory bowel disease, the traditional treatment approaches used, the role of TNF alpha in disease pathogenesis, and the value of infliximab in treatment.
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PMID:Therapeutic potential of infliximab in inflammatory bowel disease. 1077 8

Despite limited understanding of therapeutic aetiopathogenesis of ulcerative colitis and Crohn's disease, there is a strong evidence base for the efficacy of pharmacological and biological therapies. It is equally important to recognise toxicity of the medical armamentarium for inflammatory bowel disease (IBD). Sulfasalazine consists of sulfapyridine linked to 5-aminosalicylic acid (5-ASA) via an azo bond. Common adverse effects related to sulfapyridine 'intolerance' include headache, nausea, anorexia, and malaise. Other allergic or toxic adverse effects include fever, rash, haemolytic anaemia, hepatitis, pancreatitis, paradoxical worsening of colitis, and reversible sperm abnormalities. The newer 5-ASA agents were developed to deliver the active ingredient of sulfasalazine while minimising adverse effects. Adverse effects are infrequent but may include nausea, dyspepsia and headache. Olsalazine may cause a secretory diarrhoea. Uncommon hypersensitivity reactions, including worsening of colitis, pancreatitis, pericarditis and nephritis, have also been reported. Corticosteroids are commonly prescribed for treatment of moderate to severe IBD. Despite short term efficacy, corticosteroids have numerous adverse effects that preclude their long term use. Adverse effects include acne, fluid retention, fat redistribution, hypertension, hyperglycaemia, psycho-neurological disturbances, cataracts, adrenal suppression, growth failure in children, and osteonecrosis. Newer corticosteroid preparations offer potential for targeted therapy and less corticosteroid-related adverse effects. Azathioprine and mercaptopurine are associated with pancreatitis in 3 to 15% of patients that resolves upon drug cessation. Bone marrow suppression is dose related and may be delayed. The adverse effects of methotrexate include nausea, leucopenia and, rarely, hypersensitivity pneumonia or hepatic fibrosis. Common adverse effects of cyclosporin include nephrotoxicity, hypertension, headache, gingival hyperplasia, hyperkalaemia, paresthesias, and tremors. These adverse effects usually abate with dose reduction or cessation of therapy. Seizures and opportunistic infections have also been reported. Antibacterials are commonly employed as primary therapy for Crohn's disease. Common adverse effects of metronidazole include nausea and a metallic taste. Peripheral neuropathy can occur with prolonged administration. Ciprofloxacin and other antibacterials may be beneficial in those intolerant to metronidazole. Newer immunosuppressive agents previously reserved for transplant recipients are under investigation for IBD. Tacrolimus has an adverse effect profile similar to cyclosporin, and may cause renal insufficiency. Mycophenolate mofetil, a purine synthesis inhibitor, has primarily gastrointestinal adverse effects. Biological agents targeting specific sites in the immunoinflammatory cascade are now available to treat IBD. Infliximab, a chimeric antibody targeting tumour necrosis factor-or has been well tolerated in clinical trials and early postmarketing experience. Additional trials are needed to assess long term adverse effects.
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PMID:Comparative tolerability of treatments for inflammatory bowel disease. 1108 48

The introduction of novel anti-tumor necrosis factor (TNF) agents has not only led to impressive new therapeutic opportunities but also resulted in uncertainty regarding their optimal use and possible side effects. Guidelines are presented here for the use of anti-TNF agents in gastrointestinal disorders. Experts were chosen from different European countries by an algorithm to avoid bias. An expert consensus on guidelines was established using a two-stage procedure of systematic Medline and abstract search for evidence and a qualifying meeting to derive recommendations. Detailed guidelines were developed for the use and the future clinical development of anti-TNF agents in inflammatory bowel disease. Grading of available evidence and grading of recommendations were performed according to AHCPR guidelines. At present infliximab is the only registered agent for Crohn's disease. Infliximab should be always used at a dose of 5 mg/kg. The guidelines define the indications both in refractory and in fistulating disease for the readministration and before surgery. Guidelines for safety and for concomitant treatments are given. Prospects, potential clinical use, and future directions for the clinical development of other anti-TNF agents are detailed. Clinical use of anti-TNF agents will be influenced by a large number of clinical trials being concluded in 2001 and 2002. It is likely that anti-TNF therapies will become an important long-term therapy for a proportion of patients with Crohn's disease. Biological agents will be followed by smaller and more stable, orally available compounds. These guidelines will be succeeded by a formal public consensus in 2002/2003.
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PMID:Use of anti-tumour necrosis factor agents in inflammatory bowel disease. European guidelines for 2001-2003. 1131 91

Crohn's disease and ulcerative colitis are two idiopathic inflammatory disorders of the GI tract. Manifestations of disease can be severe and lead to long term therapy with a variety of medications and/or surgery. Standard medical therapy consists of agents that either treat suppurative complications or modulate the inflammatory cascade in a nonspecific manner. Many specific chemokine and cytokine effectors that promote intestinal inflammation have been identified. Such work has led to experimental clinical trials with a variety of cytokine antagonists. Compounds directed against one such cytokine, tumor necrosis factor alpha (TNF), have demonstrated the greatest clinical efficacy to date. This is consistent with scientific observations that suggest a central role for TNF in the inflammatory cascade. Infliximab is a chimeric monoclonal antibody against TNF that has been demonstrated to be effective for the treatment of Crohn's disease. Infliximab is Food and Drug Administration approved for the treatment of Crohn's disease. There exist several other TNF antagonists in various phases of investigation, including the monoclonal antibody CDP 571, the fusion peptide etanercept, the phosphodiesterase inhibitor oxpentifylline, and thalidomide. The clinical efficacy of these agents and the role of TNF in the pathogenesis of inflammatory bowel disease is reviewed.
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PMID:Integrating anti-tumor necrosis factor therapy in inflammatory bowel disease: current and future perspectives. 1146 23

Lymphoma complicating inflammatory bowel disease is well described. Whether the risk of lymphoma is increased by immunosuppressive treatment with azathioprine, 6-mercaptopurine or infliximab is a common concern among patients and physicians considering using these agents. This review aims to quantify the lymphoma risk in inflammatory bowel disease and the added risk attributable to these treatments. The evidence from published cases is that lymphomas occur at sites of active inflammatory bowel disease more often than expected for this to be a chance association. Studies on inflammatory bowel disease populations are conflicting, with some follow-up studies from large inflammatory bowel disease clinics showing an increase in lymphoma incidence, while other population-based studies show little or no increase in risk of lymphoma. A small increase in lymphoma risk in inflammatory bowel disease, perhaps 2-3-fold, may be compatible with both sets of data. Studies of the risks associated with immuno- suppression are less satisfactory, with smaller numbers of patients and relatively short follow-up. The available evidence would support a further increase in lymphoma risk associated with immunosuppressive treatment in inflammatory bowel disease of around fivefold compared to no immunosuppressive use, and tenfold compared to the general population. The risks appear to be less than that associated with renal and hepatic transplant-related immunosuppression. Infliximab treatment is still too new to make a full assessment of its long-term safety, but post-marketing surveillance currently suggests that lymphoma risk may not be any greater than that associated with azathioprine and 6-mercaptopurine. Population-wide surveillance for lymphoma in inflammatory bowel disease would be required to narrow the confidence intervals on these estimates of lymphoma risk in inflammatory bowel disease and immunosuppressive treatment.
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PMID:Review article: the risk of lymphoma associated with inflammatory bowel disease and immunosuppressive treatment. 1147 12

This review describes the pharmacokinetics of the major drugs used for the treatment of inflammatory bowel disease. This information can be helpful for the selection of a particular agent and offers guidance for effective and well tolerated regimens. The corticosteroids have a short elimination half-life (t1/2beta) of 1.5 to 4 hours, but their biological half-lives are much longer (12 to 36 hours). Most are moderate or high clearance drugs that are hepatically eliminated, primarily by cytochrome P450 (CYP) 3A4-mediated metabolism. Prednisone and budesonide undergo presystemic elimination. Any disease state or comedication affecting CYP3A4 activity should be taken into account when prescribing corticosteroids. Depending on the preparation used, 10 to 50% of an oral or rectal dose of mesalazine is absorbed. Rapid acetylation in the intestinal wall and liver (t1/2beta 0.5 to 2 hours) and transport probably by P-glycoprotein affect mucosal concentrations of mesalazine, which apparently determine clinical response. Any clinical condition influencing the release and topical availability of mesalazine might modify its therapeutic potential. Metronidazole has high (approximately 90%) oral bioavailability, with hepatic elimination characterised by a t1/2beta of 6 to 10 hours and a total clearance of about 4 L/h/kg. Ciprofloxacin is largely excreted unchanged both renally (about 45% of dose) and extrarenally (25%), with a relatively short t1/2beta (3.5 to 7 hours). Thus, renal function affects the systemic availability of ciprofloxacin. Both mercaptopurine and its prodrug azathioprine are metabolised to active compounds (6-thioguanine nucleotides; 6-TGN) by hypoxanthine-guanine phosphoribosyltransferase and to inactive metabolites by the polymorphically expressed thiopurine S-methyltransferase (TPMT) and xanthine oxidase. Patients with low TPMT activity have a higher risk of developing haemopoietic toxicity. Both mercaptopurine and azathioprine have a short t1/2beta (1 to 2 hours), but the t1/2beta of 6-TGN ranges from 3 to 13 days. Therapeutic response seems to be related to 6-TGN concentration. Almost complete bioavailability has been observed after intramuscular and subcutaneous administration of methotrexate, which is predominantly (85%) excreted as unchanged drug with a t1/2beta of up to 50 hours. Thus, renal function is the major determinant for disposition of methotrexate. Cyclosporin is slowly and incompletely absorbed. It is extensively metabolised by CYP3A4/5 in the liver and intestine (median t1/2beta and clearance 7.9 hours and 0.46 L/h/kg, respectively), and inhibitors and inducers of CYP3A4 can modify response and toxicity. Infliximab is predominantly distributed to the vascular compartment and eliminated with a t1/2beta between 10 and 14 days. No accumulation was observed when it was administered at intervals of 4 or 8 weeks. Methotrexate may reduce the clearance of infliximab from serum.
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PMID:Pharmacokinetic considerations in the treatment of inflammatory bowel disease. 1170 60


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