Infliximab inflammatory bowel disease

Three monoclonal antibodies to human TNF are approved for the treatment of inflammatory bowel disease infliximab, adalimumab, and certolizumab (Table 62-3). Infliximab and adalimumab are antibodies of the IgGi subclass. Certolizumab is a recombinant antibody that contains an Fab fragment that is conjugated to polyethylene glycol (PEG) but lacks an Fc portion. The Fab portions of infliximab and certolizumab are chimeric mouse-human antibodies but adalimumab is fully humanized. Infliximab is administered as an intravenous infusion. At therapeutic doses of 5-10 mg/kg, the half-life of infliximab is approximately 8-10 days, resulting in plasma disappearance of antibodies over 8-12 weeks. Adalimumab and certolizumab are administered by subcutaneous injection. The half-life for both is approximately 2 weeks. 

DRUGS ACTING ON THE GASTROINTESTINAL TRACT DRUGS USED TO TREAT INFLAMMATORY BOWEL DISEASE Infliximab... 

Infliximab Anti-TNFa Inflammatory bowel disease, rheumatoid arthritis, ankylosing spondylitis... 

Anticytokine antibodies Infliximab Chimeric (mouse/human) monoclonal antibody against TNEa. Effective in the treatment of severe forms of rheumatoid arthritis where it can halt disease progression, or inflammatory bowel disease (EBD). 

Lichtenstein GR et al. American Gastroenterological Association Institute technical review on corticosteroids, immunomodulators, and infliximab in inflammatory bowel disease. Gastroenterology 2006 130 940. [PMID 16530532]... 

A dysregulation of the ThI T cell response is present in inflammatory bowel disease, especially Crohn s disease. One of the key proinflammatory cytokines in the ThI response is TNF-c. Infliximab is a chimeric mouse-human monoclonal antibody to human TNF-tr. It consists of human IgGl constant regions, human flight chains and transplanted monoclonal murine variable regions that have a high affinity for TNF-er The molecule is 25% murine and 75% human. 

Several malignancies have developed in patients who were treated with infliximab. However, the observed rates may be similar to those expected in patients with inflammatory bowel disease. 

Kirman I, Whelan RL, Nielsen OH. Infliximab mechanism of action beyond TNF-alpha neutralization in inflammatory bowel disease. Eur J Gastroenterol Hepatol 2004 16 639-41. 

Infliximab is a chimeric anti TNF-a monoclonal antibody containing a human constant region and a murine variable region. It binds with high affinity to TNF-a and prevents the cytokine from binding to its receptors. It is used to treat rheumatoid arthritis and inflammatory bowel disease (Louie et al., 2003). 

In a retrospective review of 361 infliximab infusions in 57 children with inflammatory bowel disease there were 35 episodes of infusion reactions (36). Female sex, previous episodes of infusion reactions, and the use of immunosuppressive therapy for less than 4 months were significant predictors of subsequent infusion reactions. 

Baig I, Storch I, Katz S. Infliximab induced eosinophilic pleural effusion in inflammatory bowel disease. Am J Gastroenterol 2002 97(Suppl) 177. 

Infliximab This humanized MAb has a mechanism similar to that of etanercept since it is targeted against TNF-a. Infliximab induces remissions in treatment-resistant Crohn s disease, but long-term efficacy has not been estabbshed. In combination with methotrexate, infliximab improves symptoms in patients with rheumatoid arthritis. It also is effective in the treatment of inflammatory bowel disease. Infusion reactions and an increased rate of infection may occur. 

Infection risk Patients receiving infliximab are more susceptible to serious infections, including mycobacterial infections [128 ] and pneumonia [129 ]. Concomitant treatment with glucocorticoids was the only independent susceptibility factor for infections in patients with inflammatory bowel disease treated with infliximab [130. ... 

Infliximab binds to the TNF-a on the surface of cells, inhibiting transmembrane TNF-a and inflammatory response (264,265). In bowel biopsies, infliximab caused apoptosis for inflammatory cells (266-268). In contrast, etanercept does not have this effect (266) this may in part explain the ineffectiveness of etanercept for Crohn s disease (269). Adalimumab and infliximab induced apoptosis in peripheral blood monocytes whereas etanercept did not (270,271). Both etanercept and infliximab induce apoptosis of macrophages in the synovium of patients with RA (272). 

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