Infliximab

Inhibition of inflammatory cytokines (Fig. 2) Humanized monoclonal anti-TNF antibodies (Infliximab (Remicade ), Adalimumab (Humira )) bind with high selectivity to human TNF-a and neutralize its activity. Thereby, infliximab decreases the effects of enhanced TNF levels during inflammatory disease such as production of proteases, chemokines, adhesion molecules, cyclooxygenase products (prostaglandins), and proinflammatory molecules such as interleukin-1 and -6. The antibodies may also recognize membrane-bound TNF-a on lymphocytes and other immune cells. These cells may subsequently become apoptotic or are eliminated via Fc-receptor-mediated phagocytosis. 

Recombinant soluble TNF-RI-IgGl fusion protein Etanercept, Enbrel is a chimeric molecule consisting of the extracellular domain of the TNF receptor I (TNF-RI) and the Fc portion of human IgGl. Two Fc domains are bound to each other via disulfide bonds, thereby yielding dimers with two binding sites for the TNF trimer. Etanercept binds with high affinity to extracellular TNF and reduces TNF activity. Etanercept is not effective in Crohn s disease, possibly because it does not lead to destiuction of membrane TNF-a expressing cells. Indications and side effects are similar to those of Infliximab and Adalimumab. 

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). 

Adalimumab Complete human antibody against TNF-a with similar properties as infliximab. 

Soluble receptor constructs Etanercept This genetically engineered drug consists of the extracellular-part of the TNF-receptor type I and the Fc portion of human IgG. Its application in rheumatoid arthritis mirrors that of infliximab. 

Commercially available dtugs used for therapeutic therapy comprise up to date mainly injectable monoclonal antibodies like Infliximab (Remicade ) and Adalimumab (Humira ) or TNF-receptor derivatives like Etanercept (Enbrel ) (Fig. 3). One possible way of action of these reagents is the neutralization of TNF, thereby blocking its inflammatory effects and dampening (auto)immune responses [3, 4]. 

G, Mayer L, Plevy S The incidence and management of infusion reactions to infliximab a large centerexperience. AmJ Gastroenterol2003 98 1315-1324. 

More data on etanercept, infliximab, and pentoxifylline are needed before any recommendations can be made... 

Maintenance of remission of Crohn s disease may be achieved with oral or topical aminosalicylate derivatives, immunosuppressants (such as azathioprine, 6-mercaptopurine, and methotrexate), or infliximab. 

Colitis Mesalamine 2.4-A.8 g/day or sulfasalazine 4-6 g/day orally If no response to mesalamine or sulfasalazine Prednisone 40-60 mg/day orally or Infliximab 5 mg/kg IV at weeks 0, 2, and 6 Taper mesalamine to 1.6-2.4 g/day or sulfasalazine 2-4 g/day orally If prednisone or infliximab were required Taper prednisone as soon as possible Give infliximab 5 mg/kg IV every 8 weeks Consider adding azathioprine or 6-MP 1.5-2.5 mg/kg per day orally... 

Oral corticosteroids may be used for patients who are unresponsive to sulfasalazine or mesalamine. Prednisone doses of 40 to 60 mg per day (or equivalent) are recommended.1 Azathioprine or 6-MP is used for patients unresponsive to corticosteroids or those who become steroid-dependent. Over a 12-month period, these agents have been shown to reduce the relapse rate to 36% versus 59% seen with placebo.1 Infliximab 5 mg/kg may also be used for patients who are unresponsive to conventional oral therapies and may reduce the need for colectomy after 3 months of treatment.35... 

Infliximab 5 mg/kg is also an option for severe UC. Cyclosporine 2 to 4 mg/kg per day given as a continuous intravenous infusion should be reserved for patients unresponsive to 7 to 10 days of intravenous corticosteroid therapy. 

Patients with fulminant disease are treated similarly, although infliximab is not indicated for this population. Patients with fulminant UC should be assessed for signs of significant systemic toxicity or colonic dilation, which may require earlier surgical intervention. 

Immunosuppressants such as azathioprine or 6-mercaptopurine can be used for unresponsive patients or those who develop corticosteroid dependency. Remission may be maintained in up to 58% of patients after 5 years of treatment.1,25 Intermittent infliximab dosing (5 mg/kg IV every 8 weeks) may be used to maintain disease remission and reduce the need for corticosteroids in patients with moderate to severe UC. Colectomy is an option for patients with progressive disease who cannot be maintained on drug therapy alone. 

May continue infliximab at maintenance doses of 5 mg/kg every 8 weeks ... 

Patients with moderate to severe active CD may be treated with oral corticosteroids, such as prednisone 40 to 60 mg daily.2 Budesonide 9 mg orally once daily may be used for moderate active CD involving the terminal ileum or ascending colon. Infliximab is an effective alternative to corticosteroid therapy for patients with moderate to severe CD, including patients with fistulizing or perianal disease.15,37-39 The recommended regimen for induction of remission is infliximab 5 mg/kg at weeks 0, 2, and 6 it is effective in inducing remission in... 

If there are no contraindications, infliximab 5 mg/kg followed by 5 mg/kg at weeks 2 and 6 may be used for severe active CD. There is no evidence that infliximab is either safe or effective for fulminant disease. 

Patients with CD are at high risk for disease relapse after induction of remission. Within 2 years, up to 80% of patients suffer a relapse therefore, most patients should be evaluated for indefinite maintenance therapy. Maintenance of remission of CD may be achieved with oral or topical aminosalicylate derivatives, immunosuppressants (such as azathioprine, 6-mercaptopurine, and methotrexate), or infliximab. 

Infliximab has been shown to maintain remission in 46% of patients compared to 23% of those treated with placebo over a 54-week period.39 The dose used to maintain remission is... 

The aminosalicylates, azathioprine, 6-MP, and infliximab are all viable options for treatment and maintenance of IBD in pediatric patients. Use of immunosuppressive therapy or infliximab may help reduce overall corticosteroid exposure. 

Infliximab is FDA category B and also appears to carry minimal risk in pregnant patients. Little is known about excretion of infliximab in breast milk, so benefit versus risk should be considered if it is used during nursing. 

Prior to initiating infliximab, obtain a tuberculin skin test to rule out latent tuberculosis. Assure that patients do not have a clinically significant systemic infection or New York Heart Association Class III or IV heart failure. 

In patients receiving infliximab, monitor for infusion-related reactions such as hypotension, dyspnea, fever, chills, or chest pain when administering intravenous doses. 

In patients with fistulae, monitor at every infliximab dosing interval for evidence of fistula closure and overall reduction in the number of fistulae. 

Infliximab (Remicade) 3-1 0 mg/kg at 0, 2, and 6 weeks then q 8 weeks IV infusion 1 -4 weeks IR (rash, urticaria, flushing, HA, fever, chills, nausea, tachycardia, dyspnea) Monitor for infection Screen for tuberculosis... 

Systemic therapies are seldom used for mild to moderate psoriasis, and are generally reserved for patients with moderate to severe psoriasis.17 29 Oral agents include sulfasalazine, acitretin, methotrexate, cyclosporine, mycophenolate mofetil, azathioprine, tacrolimus, and hydroxyurea. Parenteral agents include the biologic response modifiers alefacept, efalizumab, etanercept, infliximab, and many others, currently at various stages of research or approval for psoriasis. 

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