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Monitoring patients treated with anti-TNF- biopharmaceuticals: assessing serum infliximab and anti-infliximab antibodies

Svenson, M.; Geborek, P.; Saxne, Tore LU and Bendtzen, K. (2007) In Rheumatology 46(12). p.1828-1834
Abstract
Objectives. Infliximab is an anti-tumour necrosis factor-alpha (TNF-alpha) mousehuman IgG1/k antibody used to treat patients with rheumatoid arthritis (RA) and other inflammatory diseases. Unfortunately, response failure and side-effects due to immunogenicity of the drug are not rare. In this study, we have compared different methods of assessing drug levels and anti-infliximab antibodies (Abs) and analysed the character of these Abs in sera of RA patients treated with infliximab for 1.5-18 months. Methods. Functional serum infliximab levels and anti-infliximab Abs were measured by fluid-phase RIAs using I-125-labelled ligands in combination with molecular size and affinity chromatography, and immune complex precipitation. Results.... (More)
Objectives. Infliximab is an anti-tumour necrosis factor-alpha (TNF-alpha) mousehuman IgG1/k antibody used to treat patients with rheumatoid arthritis (RA) and other inflammatory diseases. Unfortunately, response failure and side-effects due to immunogenicity of the drug are not rare. In this study, we have compared different methods of assessing drug levels and anti-infliximab antibodies (Abs) and analysed the character of these Abs in sera of RA patients treated with infliximab for 1.5-18 months. Methods. Functional serum infliximab levels and anti-infliximab Abs were measured by fluid-phase RIAs using I-125-labelled ligands in combination with molecular size and affinity chromatography, and immune complex precipitation. Results. Anti-infliximab Abs were predominantly IgG, 36% being IgG4, and half the immune complexes were lambda-light-chain-positive. Ab titres were associated with inhibition of TNF binding to the drug, and low trough levels of infliximab were most frequent in anti-infliximab Ab-positive sera. Cross-binding to two other anti-TNF drugs was not observed. Detection of anti-infliximab Abs by solid-phase RIA using cross-binding of plastic-fixed and soluble infliximab exhibited low sensitivity and the data were inconsistent with results obtained from binding of the Abs to soluble infliximab. Conclusions. Specific and neutralizing anti-infliximab antibodies develop in RA patients treated with infliximab, and that low trough levels of functional infliximab are associated with the presence of such antibodies. The most sensitive antibody assay involved binding to soluble and intact infliximab. Assessments of bioavailability and immunogenicity of anti-TNF biologicals may be used to optimize dose regimens and prevent prolonged use of inadequate therapy. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
anti-allotypic antibodies, radioimmunoassay, antibodies, rheumatoid arthritis, tumour necrosis factor-alpha
in
Rheumatology
volume
46
issue
12
pages
1828 - 1834
publisher
Oxford University Press
external identifiers
  • wos:000251197900018
  • scopus:36448985258
ISSN
1462-0332
DOI
10.1093/rheumatology/kem261
language
English
LU publication?
yes
id
d51372af-c6b9-4ce6-aaf4-855b618a8731 (old id 968764)
date added to LUP
2008-01-30 09:11:23
date last changed
2017-11-19 04:06:31
@article{d51372af-c6b9-4ce6-aaf4-855b618a8731,
  abstract     = {Objectives. Infliximab is an anti-tumour necrosis factor-alpha (TNF-alpha) mousehuman IgG1/k antibody used to treat patients with rheumatoid arthritis (RA) and other inflammatory diseases. Unfortunately, response failure and side-effects due to immunogenicity of the drug are not rare. In this study, we have compared different methods of assessing drug levels and anti-infliximab antibodies (Abs) and analysed the character of these Abs in sera of RA patients treated with infliximab for 1.5-18 months. Methods. Functional serum infliximab levels and anti-infliximab Abs were measured by fluid-phase RIAs using I-125-labelled ligands in combination with molecular size and affinity chromatography, and immune complex precipitation. Results. Anti-infliximab Abs were predominantly IgG, 36% being IgG4, and half the immune complexes were lambda-light-chain-positive. Ab titres were associated with inhibition of TNF binding to the drug, and low trough levels of infliximab were most frequent in anti-infliximab Ab-positive sera. Cross-binding to two other anti-TNF drugs was not observed. Detection of anti-infliximab Abs by solid-phase RIA using cross-binding of plastic-fixed and soluble infliximab exhibited low sensitivity and the data were inconsistent with results obtained from binding of the Abs to soluble infliximab. Conclusions. Specific and neutralizing anti-infliximab antibodies develop in RA patients treated with infliximab, and that low trough levels of functional infliximab are associated with the presence of such antibodies. The most sensitive antibody assay involved binding to soluble and intact infliximab. Assessments of bioavailability and immunogenicity of anti-TNF biologicals may be used to optimize dose regimens and prevent prolonged use of inadequate therapy.},
  author       = {Svenson, M. and Geborek, P. and Saxne, Tore and Bendtzen, K.},
  issn         = {1462-0332},
  keyword      = {anti-allotypic antibodies,radioimmunoassay,antibodies,rheumatoid arthritis,tumour necrosis factor-alpha},
  language     = {eng},
  number       = {12},
  pages        = {1828--1834},
  publisher    = {Oxford University Press},
  series       = {Rheumatology},
  title        = {Monitoring patients treated with anti-TNF- biopharmaceuticals: assessing serum infliximab and anti-infliximab antibodies},
  url          = {http://dx.doi.org/10.1093/rheumatology/kem261},
  volume       = {46},
  year         = {2007},
}