Article: Infliximab

Infliximab (Remicade®) is a powerful drug used to treat auto-immune disorders like Crohn's disease and rheumatoid arthritis. Infliximab is known as a "chimeric monoclonal antibody" (the term "chimeric" refers to the use of both mouse and human components of the drug i.e. mouse binding VK and VH domains and human constant Fc domains). The drug reduces the amount of active TNF-α (tumour necrosis factor alpha) in the body by binding to it and preventing it from signaling the receptors for TNF-α on the surface of cells. TNF-α is one of the key cytokines that triggers and sustains the inflammation response. Remicade was invented by Junming Le and Jan Vilcek at New York University School of Medicine and developed by Centocor, a pharmaceutical company owned by Johnson & Johnson.^[1]

In the United States, Infliximab is indicated (approved by the US Food and Drug Administration (FDA)) for the treatment of rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, ulcerative colitis, adult Crohn's disease and pediatric Crohn's disease. It is the only anti-TNF alpha biologic in its class with an indication for the latter 3 diseases.

Remicade is administered by intravenous infusion, typically at a clinic or hospital. It cannot be administered orally, because the digestive system would destroy the drug.

Pharmacology

According to product labeling (the statements which accompany a prescription drug and which must be approved approved by the US FDA), infliximab neutralizes the biological activity of TNF alpha (TNFα) by binding with high affinity to the soluble (free floating in the blood) and transmembrane (located on the outer membranes of T cells and similar immune cells) forms of TNFα and inhibits or prevents the effective binding of TNFα with its receptors.

Infliximab has high specificity for TNF alpha, and does not neutralize TNF beta (TNFβ, also called lymphotoxin α), a related but less inflammatory cytokine that utilizes the same receptors as TNFα. Biological activities that are attributed to TNFα include: induction of proinflammatory cytokines such as interleukin (IL) 1 and IL 6, enhancement of leukocyte movement or migration from the blood vessels into the tissues by increasing the permeability of endothelial layer of blood vessels; and increasing the release of adhesion molecules. Infliximab prevents disease in transgenic mice (a special type of mice that are biologically engineered to produce a human form of TNF alpha and which are used to test the results of these drugs that might be expected in humans). These experimental mice develop arthritis as a result of their production of human TNFα, and when administered after disease onset, infliximab allows eroded joints to heal.

Safety

According to the product labeling of infliximab, etanercept, and adalimumab, these drugs are in the class of immunosuppressants. After a number of studies and reports of adverse reactions in patients receiving anti-TNF alpha therapy (including serious and sometimes fatal blood disorders, infections, rare reports of lymphoma and solid tissue cancers, rare reports of serious liver injury, and rare reports of demyelinating central nervous system disorders), the FDA issued a warning to doctors appearing in the respective product labeling of these drugs instructing them to screen and monitor potential patients more carefully.

Other uses

Case studies have been done into other uses of infliximab, such as to treat skin diseases. Remicade (infliximab) has been approved for treating ankylosing spondylitis, Crohn's disease, psoriatic arthritis, psoriasis (EU), rheumatoid arthritis, and ulcerative colitis.

There have been numerous case reports of the efficacy of infliximab in various inflammatory skin conditions diseases; psoriasis, in which increased TNFα has been demonstrated, is the most promising indication.^[2]

See also

• Adalimumab
• Etanercept
• Monoclonal antibody
• Tumor necrosis factor

Reference

1. ^ Knight DM, Trinh H, Le J, Siegel S, Shealy D, McDonough M, Scallon B, Moore MA, Vilcek J, Daddona P, et al. Construction and initial characterization of a mouse-human chimeric anti-TNF antibody. Mol Immunol 1993;30:1443-53. PMID 8232330.
2. ^ Gupta AK, Skinner AR. A review of the use of infliximab to manage cutaneous dermatoses. J Cutan Med Surg 2004;8:77-89. PMID 15685387.