title: Individual medicine in inflammatory bowel disease: monitoring bioavailability, pharmacokinetics and immunogenicity of anti-tumour necrosis factor-alpha antibodies.
abstract: Antibody constructs targeting tumour necrosis factor-alpha (TNF) have become important in the management of several chronic immunoinflammatory diseases. Four recombinant anti-TNF drugs are currently approved for clinical use in patients with various chronic inflammatory diseases, three of which are effective in chronic inflammatory bowel disease. These proteins can dramatically lower disease activity and, in some patients, induce remission. Unfortunately, however, not all patients respond favourably to anti-TNF antibodies. For example, patients suffering from Crohn's disease do not benefit from etanercept, and some patients treated with the other anti-TNF constructs either do not respond at all (primary response failure), or they respond initially but have later relapses (secondary response failure) despite increased dosage and/or more frequent administration of the drugs. The reason(s) for these response failures are not clear but inter-individual and even intra-individual differences in bioavailability and pharmacokinetics may contribute. Furthermore, immunogenicity of the drugs, causing patients to develop anti-drug antibodies (ADAs), contributes to treatment failure. Monitoring patients for circulating levels of functional anti-TNF drugs and ADAs is therefore warranted so that treatment can be tailored to the individual patient (individual medicine or personal medicine) in order that effective and economical long-term therapy can be given with minimal risks to the patients.
authors.affiliation: Institute for Inflammation Research, Rigshospitalet National University Hospital, Blegdamsvej 9, Copenhagen, Denmark. kben@dbmail.dk
authors.forename: Klaus
authors.initials: K
authors.lastname: Bendtzen
authors.forename: Mark
authors.initials: M
authors.lastname: Ainsworth
authors.forename: Casper
authors.initials: C
authors.lastname: Steenholdt
authors.forename: Ole Østergaard
authors.initials: OØ
authors.lastname: Thomsen
authors.forename: Jørn
authors.initials: J
authors.lastname: Brynskov
mesh_terms: D000068879:Adalimumab; D000893:Anti-Inflammatory Agents / Q000493:pharmacokinetics / Q000494:pharmacology*; D000906:Antibodies / Q000276:immunology / Q000494:pharmacology*; D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics / Q000494:pharmacology; D061067:Antibodies, Monoclonal, Humanized; D001682:Biological Availability; D000068582:Certolizumab Pegol; D000068800:Etanercept; D005765:Gastrointestinal Agents / Q000493:pharmacokinetics / Q000494:pharmacology*; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000494:pharmacology; D007074:Immunoglobulin G / Q000494:pharmacology; D007167:Immunotherapy / Q000379:methods; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy* / Q000276:immunology*; D000069285:Infliximab; D011092:Polyethylene Glycols / Q000493:pharmacokinetics / Q000494:pharmacology; D011863:Radioimmunoassay; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000276:immunology
chemical_list: D000893:Anti-Inflammatory Agents; D000906:Antibodies; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D005765:Gastrointestinal Agents; D007140:Immunoglobulin Fab Fragments; D007074:Immunoglobulin G; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D011092:Polyethylene Glycols; D000069285:Infliximab; D000068879:Adalimumab; D000068800:Etanercept; D000068582:Certolizumab Pegol