TY - JOUR
T1 - Individual medicine in inflammatory bowel disease: monitoring bioavailability, pharmacokinetics and immunogenicity of anti-tumour necrosis factor-alpha antibodies
AU - Bendtzen, Klaus
AU - Ainsworth, Mark
AU - Steenholdt, Casper
AU - Thomsen, Ole Østergaard
AU - Brynskov, Jørn
AU - Bendtzen, Klaus
AU - Ainsworth, Mark
AU - Steenholdt, Casper
AU - Thomsen, Ole Østergaard
AU - Brynskov, Jørn
N1 - Keywords: Anti-Inflammatory Agents; Antibodies; Antibodies, Monoclonal; Biological Availability; Gastrointestinal Agents; Humans; Immunoglobulin Fab Fragments; Immunoglobulin G; Immunotherapy; Inflammatory Bowel Diseases; Polyethylene Glycols; Radioimmunoassay; Receptors, Tumor Necrosis Factor; Tumor Necrosis Factor-alpha
PY - 2009/1/1
Y1 - 2009/1/1
N2 - 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.
AB - 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.
U2 - 10.1080/00365520802699278
DO - 10.1080/00365520802699278
M3 - Journal article
C2 - 19140087
SN - 0036-5521
VL - 44
SP - 774
EP - 781
JO - Scandinavian Journal of Gastroenterology
JF - Scandinavian Journal of Gastroenterology
IS - 7
ER -