Clinical Immunology Society

Infliximab

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Compound Name:InfliximabMolecular Target:TNF? (Tumor Necrosis Factor-alpha)Molecular Structure:chimeric IgG1k, recombinant monoclonal antibodyLicensed Indication:Rheumatoid arthritis (in combination with methotrexate); Ankylosing spondylitis; Psoriatic arthritis; Plaque psoriasis; Crohn's disease; Pediatric Crohn's disease; Ulcerative colitis; Pediatric ulcerative colitisManufacturer and/or Distributor:Janssen BiotechInitial FDA Approval:1998Summary:Infliximab (Remicade) is a recombinant chimeric IgG1k monoclonal antibody that binds specifically to both soluble and cell-surface bound forms of TNFα, thereby blocking interaction of TNFα with the p55 and p75 surface TNF receptors. It is administered as an intravenous infusion, generally every 4 to 8 weeks. TNFα is a central mediator of inflammation and is known to be dysregulated in a range of autoimmune diseases. TNFα blockers are thought to provide effective immunosuppression through a variety of mechanisms: neutralization of soluble and/or membrane-bound TNFα, direct cellular toxicity via complement-mediated lysis and/or antibody-dependent cytotoxicity, and induction of apoptosis or other downregulatory effects. Infliximab was first licensed for use in Crohn's disease in 1998. Since then, additional indications have expanded to include rheumatoid arthritis, psoriatic arthritis, severe chronic plaque psoriasis, ulcerative colitis, and ankylosing spondylitis. In rheumatoid arthritis it is indicated for use with weekly methotrexate, which both increases the efficacy of the therapy, and reduces the incidences of HACA formation (Human Anti-Chimeric Antibody, i.e., an immune response by the patient specifically directed at the infliximab molecule). Important adverse reactions include increased risk of infection, particularly TB, invasive fungal disease, bacterial sepsis, opportunistic infections, and hepatitis B reactivation. In 2011, the label was updated to specifically include the risk from infection with intracellular bacterial pathogens, Listeria and Legionella. Live vaccines should not be given to patients being treated with infliximab. Lymphoma and others malignancies are of concern, and post-licensing surveillance has noted an increased incidence of hepatosplenic T-cell lymphomas associated with concomitant 6-mercaptopurine or azathioprine use, particularly in adolescent or young adult males with Crohn’s disease or ulcerative colitis. The black box label has also been updated to highlight the more general risk of lymphomas and other malignancies, including melanoma and Merkel cell carcinoma, in children and adolescents. Other associated risks are hepatotoxicity, heart failure, cytopenias, demyelinating disease, lupus, and hypersensitivity.References

Package Insert: http://www.remicade.com/hcp/remicade/assets/hcp_ppi.pdf



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7. Akobeng AA, Sandborn WJ, Bickston SJ, Chande N, Shackelton LM et al. Tumor necrosis factor-alpha antagonists twenty years later: what do Cochrane reviews tell us? Inflamm Bowel Dis. 2014 Nov;20(11):2132-41.
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8. Narula N, Marshall JK, Colombel JF, Leontiadis GI, Williams JG et al. Systematic Review and Meta-Analysis: Infliximab or Cyclosporine as Rescue Therapy in Patients With Severe Ulcerative Colitis Refractory to Steroids. Am J Gastroenterol. 2016 Feb 9.
http://www.ncbi.nlm.nih.gov/pubmed/26856754

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