Infliximab neutralizes the biological activity of TNFα by binding with high affinity to the soluble and transmembrane forms of TNFα and inhibits binding of TNFα with its receptors. Infliximab does not neutralize TNFα (lymphotoxin-α), a related cytokine that utilizes the same receptors as TNFα. Biological activities attributed to TNFα include: induction of pro inflammatory cytokines such as interleukins (IL) 1 and 6, enhancement of leukocyte migration by increasing endothelial layer permeability and expression of adhesion molecules by endothelial cells and leukocytes, activation of neutrophil and eosinophil functional activity, induction of acute phase reactants and other liver proteins, as well as tissue degrading enzymes produced by synoviocytes and/or chondrocytes. Cells expressing transmembrane TNFα bound by infliximab can be lysed in vitro or in vivo. Infliximab inhibits the functional activity of TNFα in a wide variety of in vitro bioassays utilizing human fibroblasts, endothelial cells, neutrophils, B and T lymphocytes and epithelial cells. The relationship of these biological response markers to the mechanism(s) by which Infliximab exerts its clinical effects is unknown. Anti-TNFα antibodies reduce disease activity in the cotton-top tamarin colitis model, and decrease synovitis and joint erosions in a murine model of collagen-induced arthritis. Infliximab prevents disease in transgenic mice that develop polyarthritis as a result of constitutive expression of human TNFα, and when administered after disease onset, allows eroded joints to heal.

Crohn’s Disease:

• Reducing signs and symptoms and inducing and maintaining clinical remission in adult patients with moderately to severely active disease who have had an inadequate response to conventional therapy.
• Reducing the number of draining enterocutaneous and rectovaginal fistulas and maintaining fistula closure in adult patients with fistulizing disease.

Pediatric Crohn’s Disease:

• Reducing signs and symptoms and inducing and maintaining clinical remission in pediatric patients with moderately to severely active disease who have had an inadequate response to conventional therapy.

Ulcerative Colitis:

• Reducing signs and symptoms, inducing and maintaining clinical remission and mucosal healing, and eliminating corticosteroid use in adult patients with moderately to severely active disease who have had an inadequate response to conventional therapy.

Pediatric Ulcerative Colitis:

• Reducing signs and symptoms and inducing and maintaining clinical remission in pediatric patients with moderately to severely active disease who have had an inadequate response to conventional therapy.

Rheumatoid Arthritis in combination with methotrexate:

• Reducing signs and symptoms, inhibiting the progression of structural damage, and improving physical function in patients with moderately to severely active disease.

Ankylosing Spondylitis:

• Reducing signs and symptoms in patients with active disease.

Psoriatic Arthritis:

• Reducing signs and symptoms of active arthritis, inhibiting the progression of structural damage, and improving physical function.

Plaque Psoriasis:

• Treatment of adult patients with chronic severe (i.e., extensive and /or disabling) plaque psoriasis who are candidates for systemic therapy and when other systemic therapies are medically less appropriate.

Crohn’s Disease: 5 mg/kg at 0, 2 and 6 weeks, then every 8 weeks. Some adult patients who initially respond to treatment may benefit from increasing the dose to 10 mg/kg if they later lose their response.

Pediatric Crohn’s Disease: 5 mg/kg at 0, 2 and 6 weeks, then every 8 weeks.

Ulcerative Colitis: 5 mg/kg at 0, 2 and 6 weeks, then every 8 weeks.

Pediatric Ulcerative Colitis: 5 mg/kg at 0, 2 and 6 weeks, then every 8 weeks.

Rheumatoid Arthritis: In conjunction with methotrexate, 3 mg/kg at 0, 2 and 6 weeks, then every 8 weeks. Some patients may benefit from increasing the dose up to 10

mg/kg or treating as often as every 4 weeks.

Ankylosing Spondylitis: 5 mg/kg at 0, 2 and 6 weeks, then every 6 weeks.

Psoriatic Arthritis and Plaque Psoriasis: 5 mg/kg at 0, 2 and 6 weeks, then every 8 weeks.

Administration

Infliximab is administered by intravenous infusion over a period of not less than 2 hours.

Infliximab doses >5 mg/kg in moderate to severe heart failure. Previous severe hypersensitivity reaction to Infliximab or known hypersensitivity to inactive components of Infliximab or to any murine proteins.

Most common adverse reactions (>10%)- infections (e.g. upper respiratory, sinusitis, and pharyngitis), infusion-related reactions, headache, and abdominal pain.

Serious infections- do not give Infliximab during an active infection. If an infection develops, monitor carefully and stop Infliximab if infection becomes serious.

Invasive fungal infections- for patients who develop a systemic illness on Infliximab, consider empiric antifungal therapy for those who reside or travel to regions where mycoses are endemic

Malignancies- the incidence of malignancies including lymphoma was greater in Infliximab treated patients than in controls. Due to the risk of HSTCL carefully assess the risk/benefit especially if the patient has Crohn’s disease or ulcerative colitis, is male, and is receiving azathioprine or 6-mercaptopurine treatment.

Hepatitis B virus reactivation- test for HBV infection before starting Infliximab. Monitor HBV carriers during and several months after therapy. If reactivation occurs, stop Infliximab and begin anti-viral therapy.

Hepatotoxicity- rare severe hepatic reactions, some fatal or

necessitating liver transplantation. Stop Infliximab in cases of jaundice and/or marked liver enzyme elevations.

Heart failure- new onset or worsening symptoms may occur.

Cytopenias- advise patients to seek immediate medical attention if signs and symptoms develop, and consider stopping Infliximab.

Hypersensitivity- serious infusion reactions including anaphylaxis or serum sickness-like reactions may occur. 

Demyelinating disease- exacerbation or new onset may occur.

Lupus-like syndrome- stop Infliximab if syndrome develops.

Live vaccines or therapeutic infectious agents- should not be given with Infliximab. Bring pediatric patients

Use in Special Populations

Pediatric Use: Infliximab has not been studied in children with Crohn’s disease or ulcerative colitis<6 years of age.

Pregnancy & Lactation

Pregnancy Category B. It is not known whether Infliximab can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity.

It is not known whether Infliximab is excreted in human milk or absorbed systemically after ingestion. Because many drugs and immunoglobulins are excreted in human milk, and because of the potential for adverse reactions in nursing infants from Infliximab, women should not breast-feed their infants while taking Infliximab.