title: Tumor necrosis factor antagonist mechanisms of action: a comprehensive review.
abstract: During the past 30 years, elucidation of the pathogenesis of rheumatoid arthritis, Crohn's disease, psoriasis, psoriatic arthritis and ankylosing spondylitis at the cellular and molecular levels has revealed that these diseases share common mechanisms and are more closely related than was previously recognized. Research on the complex biology of tumor necrosis factor (TNF) has uncovered many mechanisms and pathways by which TNF may be involved in the pathogenesis of these diseases. There are 3 TNF antagonists currently available: adalimumab, a fully human monoclonal antibody; etanercept, a soluble receptor construct; and infliximab, a chimeric monoclonal antibody. Two other TNF antagonists, certolizumab and golimumab, are in clinical development. The remarkable efficacy of TNF antagonists in these diseases places TNF in the center of our understanding of the pathogenesis of many immune-mediated inflammatory diseases. The purpose of this review is to discuss the biology of TNF and related family members in the context of the potential mechanisms of action of TNF antagonists in a variety of immune-mediated inflammatory diseases. Possible mechanistic differences between TNF antagonists are addressed with regard to their efficacy and safety profiles.
authors.affiliation: Abbott Bioresearch Center, Worcester, MA, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Tracey
authors.forename: Lars
authors.initials: L
authors.lastname: Klareskog
authors.forename: Eric H
authors.initials: EH
authors.lastname: Sasso
authors.forename: Jochen G
authors.initials: JG
authors.lastname: Salfeld
authors.forename: Paul P
authors.initials: PP
authors.lastname: Tak
mesh_terms: D000068879:Adalimumab; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000009:adverse effects / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D061067:Antibodies, Monoclonal, Humanized; D017209:Apoptosis / Q000187:drug effects; D001842:Bone and Bones / Q000187:drug effects / Q000276:immunology; D002356:Cartilage / Q000187:drug effects / Q000276:immunology; D000068582:Certolizumab Pegol; D000068800:Etanercept; D006801:Humans; D007107:Immune System / Q000187:drug effects* / Q000378:metabolism; D007140:Immunoglobulin Fab Fragments / Q000494:pharmacology; D007074:Immunoglobulin G / Q000494:pharmacology; D007249:Inflammation / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D000069285:Infliximab; D008024:Ligands; D008233:Lymphotoxin-alpha / Q000378:metabolism; D015394:Molecular Structure; D011092:Polyethylene Glycols / Q000494:pharmacology; D011961:Receptors, Fc / Q000187:drug effects; D018124:Receptors, Tumor Necrosis Factor; D015398:Signal Transduction / Q000187:drug effects; D013329:Structure-Activity Relationship; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D007140:Immunoglobulin Fab Fragments; D007074:Immunoglobulin G; D008024:Ligands; D008233:Lymphotoxin-alpha; D011961:Receptors, Fc; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D011092:Polyethylene Glycols; D000069285:Infliximab; D000068879:Adalimumab; D000068800:Etanercept; D000068582:Certolizumab Pegol