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)

At this time, standard therapy for treatment of inflammatory bowel disease includes the use of glucocorticoids for moderate to severe Crohn's disease, severe ulcerative colitis, and moderate ulcerative colitis failing mesalamine. Although the majority of patients will have clinical improvement with glucocorticoids, a substantial minority of patients will later flare with attempts to withdraw therapy. Given the numerous potential side effects associated with glucocorticoids, every effort should be made to switch these patients to a less toxic medication. Historically, the most reliable agents have been azathioprine or 6-mercaptopurine. Infliximab is a relatively new medication but would be expected to be beneficial for weaning glucocorticoids for Crohn's disease patients. Methotrexate is another alternative for Crohn's disease. Budesonide and CDP571 are still in developmental phases but likely will be helpful in managing this patient population. Mesalamine, cyclosporine, mycofenalate mofetil, and thalidomide have less data available to support their use but may be helpful for some patients. 6-Thioguanine may be an alternative to patients who do not tolerate 6-mercaptopurine or azathioprine.
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PMID:Managing the glucocorticoid dependent inflammatory bowel disease patient. 1172 77

Pro-inflammatory cytokines such as TNF-alpha and IL-6 play a role in the pathogenesis of inflammatory bowel disease (IBD). Recent advances in the treatment with IBD patients, in particular Crohn's disease, are the use of anti-cytokine monoclonal antibodies against TNF-alpha. Three types of anti-human TNF-alpha antibodies have been developed. Infliximab is a chimeric antibody containing Fab portion of anti-human TNF-alpha mouse IgG and Fc portion of human IgG. CDP571 is a humanized (-95% human residues) monoclonal antibody, and is potentially less immunogenic than chimeric antibody. In this paper, we summarize the recent reports describing the clinical efficacy of these antibodies in the treatment of Crohn's disease.
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PMID:[Treatment of Crohn's disease by anti-cytokine monoclonal antibodies]. 1180 21

In rheumatoid arthritis and inflammatory bowel disease, such as Crohn's disease, certain immunological abnormalities are considered as its cause, but the fundamental mechanism remains unclear. However, recent researches revealed that inflammatory cytokines, such as TNF-alpha, IL-1 and IL-6, are greatly involved in these immunological abnormalities. This led to the development of anti-cytokine therapy using monoclonal antibodies to these cytokines. Among them, Infliximab, a chimeric monoclonal antibodies to TNF-alpha, is most clinically applied and marked therapeutic effect is seen in various diseases.
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PMID:[Infliximab(chimeric monoclonal antibody to tumor necrosis factor alpha)]. 1190 62

Pyoderma gangrenosum is an extraintestinal manifestation of inflammatory bowel disease requiring meticulous medical and/or surgical treatment. We describe a 46-year-old patient who developed harsh pyoderma gangrenosum during a severe flare-up of the underlying Crohn disease of the terminal ileum. The patient responded favorably to treatment with infliximab-the chimeric antibody against tumor necrosis factor-alpha. The drug was administered intravenously at a dose 5 mg/kg/BW at baseline and weeks 2 and 6. Abdominal signs and symptoms as well as the skin lesions improved markedly before the second infusion. The patient is presently on infliximab maintenance regimen at a dose of 5 mg/kg/BW being administered as a 3 dose loading regimen at 0, 2 and 6 weeks with a treatment-free interval of 10 weeks until the next loading dose. The skin lesions remained in remission. Infliximab is a promising therapeutic modality for patients with Crohn disease and pyoderma gangrenosum.
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PMID:Favorable response to infliximab treatment in a patient with active Crohn disease and pyoderma gangrenosum. 1219 Jan 4

Tumour necrosis factor (TNF) plays an important role in mediating the inflammation of inflammatory bowel disease, in particular, Crohn's disease. Strategies aimed at reducing tumour necrosis factor in patients with inflammatory bowel disease include the mouse/human chimeric monoclonal antibody infliximab, the humanized monoclonal antibody CDP571, the human soluble TNF p55 receptor onercept, the human monoclonal antibody D2E7 (adalimumab), the anti-TNF human antibody Fab' fragment-polyethelene glycol (PEG) conjugate CDP870, and the small molecules thalidomide and CNI-1493 (MAP-kinase inhibitor). Infliximab is effective for treating active Crohn's disease, maintaining remission, closing fistulas, maintaining fistula closure, and treating ankylosing spondylitis. Infliximab is also being investigated for the treatment of ulcerative colitis. Side-effects occurring in patients treated with infliximab include human anti-chimeric antibodies, infusion reactions, delayed hypersensitivity reactions, formation of autoantibodies, and, in rare circumstances, drug-induced lupus and serious infections, including tuberculosis. CDP571 is effective for treating active Crohn's disease, steroid sparing, and possibly for closing fistulas and maintaining remission. Side-effects occurring in patients treated with CDP571 include anti-idiotype antibodies, infusion reactions and the formation of autoantibodies. A controlled trial of etanercept in patients with Crohn's disease was negative. Pilot studies with onercept, thalidomide, and CNI-1493 have suggested benefit for Crohn's disease. There are no published data on the efficacy of adalimumab (D2E7) or CDP870 for either Crohn's disease or ulcerative colitis. Anti-tumour necrosis factor therapies are effective for the treatment of Crohn's disease and are being investigated for ulcerative colitis.
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PMID:Strategies for targeting tumour necrosis factor in IBD. 1261 86

Peristomal pyoderma gangrenosum (PPG) is a variant of pyoderma gangrenosum (PG) that is more refractory to treatment. It is a cause of severe morbidity and poses a therapeutic challenge for the clinician. Infliximab (Remicade(R); Centocor, Malvern, PA, USA) is a chimeric monoclonal antibody directed against tumour necrosis factor-alpha that has been proven to be effective in the treatment of inflammatory bowel disease (IBD) and rheumatoid arthritis. Currently, very few reports exist documenting its use in the treatment of PG and none in the treatment of PPG. We describe our experience of treating three patients with IBD-associated PPG with infliximab. All patients tolerated the drug without significant side-effects. Two patients with PPG recovered completely following the administration of infliximab, and one patient had a partial response to the drug. We conclude that infliximab appears to be a safe and effective therapeutic alternative in patients with PPG.
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PMID:Infliximab for peristomal pyoderma gangrenosum. 1275 45

The first-line therapy for inflammatory bowel disease flares is typically medical in nature. Glucocorticoids are a mainstay for the treatment of severe inflammatory bowel disease. Aminosalicylates are efficacious in the treatment of active mild- to- moderate disease. Infliximab, a chimeric monoclonal anti-TNF alpha antibody can be used in refractory Crohn's disease. The recurrence rate after surgery or medical therapy is high. Therefore the introduction of a maintenance therapy is important in patients with repetitive flares. In patients with ulcerative colitis aminosalicylates are useful as maintenance therapy. In severe ulcerative colitis or in Crohn's disease immune suppressive strategies such as a therapy with azathioprine, 6-mercaptopurine or methotrexate should be considered. In Crohn's patients with fistula surgical treatment or a therapy with antibiotics, immunosuppressants or infliximab is recommended.
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PMID:[Does conservative therapy of chronic inflammatory bowel diseases still play a role?]. 1281 33

Infliximab, a chimeric mouse-human monoclonal antibody, blocks the action of tumor necrosis factor-alpha and is a highly effective treatment for several inflammatory disorders, including inflammatory bowel disease and rheumatoid arthritis. Although safety data are encouraging, immunosuppressive sequelae may result. We report the acute development of multiple squamous cell carcinomas and keratoacanthomas in a patient receiving infliximab for rheumatoid arthritis.
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PMID:Acute development of multiple keratoacanthomas and squamous cell carcinomas after treatment with infliximab. 1509 33

Recent controlled and uncontrolled trial data in inflammatory bowel disease have suggested several new avenues of possible therapies and refined our understanding of the uses and selectiveness of anti-tumor necrosis factor (TNF)-based therapies. Infliximab remains the only proven effective anti-TNF therapy, whereas others have proven ineffective (etanercept, CDP-571) or of limited utility (thalidomide, CDP-870). A Crohn's disease Clinical trial Evaluating infliximab in a New long-term Treatment regimen (ACCENT I) and ACCENT II trials supported the strategy of using 5 to 10 mg/kg of infliximab on an every 8-week basis for maintenance of remission, although in clinical practice many physicians take variable approaches to maintenance of remission dosing schedules. On the other hand, no controlled trial data to date have supported the use of infliximab in ulcerative colitis. Therapies utilizing novel mechanistic approaches, such as hematopoietic growth factors, mitogen-activated protein (MAP)-kinase inhibition, and peroxisome proliferator activated receptor gamma ligand receptor binding have shown promise in small uncontrolled trials and await confirmation of their utility in randomized, placebo-controlled trials. Newer biologic (natalizumab) or cytokine-based therapies (monoclonal antibody to interleukin-6) have shown preliminary evidence of efficacy in controlled trials, but neither have yet been approved by the US Food and Drug Administration and, therefore, have not been commercialized. However, tacrolimus, a potent calcineurin inhibitor and inhibitor of interleukin-2 expression, has shown efficacy in Crohn's disease, albeit at the cost of substantial potential toxicity.
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PMID:Newer Therapies for Inflammatory Bowel Disease. 1514 78

Infliximab, the chimeric monoclonal immunoglobulin (Ig)G1 antibody to tumor necrosis factor (TNF) has changed our therapy of Crohn's disease. Infliximab is indicated in refractory luminal and fistulizing Crohn's disease. In patients with luminal disease, a single intravenous (i.v.) dose of 5 mg/kg is efficacious; in fistulizing disease, an i.v. loading therapy of 5 mg/kg at weeks 0, 2, and 6 is advocated. Because the majority of patients will relapse if not re-treated, a long-term strategy is necessary. The optimal long-term approach is systematic re-treatment with 5 mg/kg every 8 weeks. Episodic therapy on relapse also is possible but is less efficacious and frequently is associated with problems resulting from the formation of antibodies to infliximab (ATI). If treatment is episodic, maintenance therapy with immunosuppression (azathioprine [AZA]/6-mercaptopurine [6-MP] or methotrexate) is mandatory. Trial data suggest that systematic maintenance with 8 weekly doses of infliximab decreases the rate of complications, hospitalizations, and surgeries. These effects probably are achieved thanks to thorough healing of the bowel. Infliximab also is indicated in treating corticosteroid-dependent Crohn's disease and extraintestinal manifestations of Crohn's disease. There are no data yet that support its use as first-line therapy. The data in ulcerative colitis (UC) are conflicting and we should await the results of 2 large controlled trials (ACT1 and ACT2) to position infliximab in the treatment of UC. Other anti-TNF strategies have been less effective than infliximab in the treatment of IBD until now. The results with thalidomide are promising but much more research into small molecules inhibiting TNF and other proinflammatory cytokines is necessary. Safety problems with antibody treatment mainly concern immunogenicity leading to infusion reactions, loss of response, and serum sickness-like delayed infusion reactions. The rate of opportunistic infections is increased mainly in patients treated concomitantly with immunosuppression. Other adverse events associated with anti-TNF strategies are demyelinating disease and worsening of congestive heart failure. Malignancy rates in patients treated with anti-TNF strategies do not seem to be increased.
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PMID:Optimizing anti-TNF treatment in inflammatory bowel disease. 1516 70


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