Abstract:
BACKGROUND:Many patients with rheumatoid arthritis are currently successfully treated with infliximab (anti-tumour necrosis factor); however, about 30% of the patients do not respond to infliximab. One of the postulated hypotheses of not responding is the fast clearance of infliximab due to the development of infliximab-anti-infliximab complexes. OBJECTIVE:To investigate the in vivo mechanism of not responding and the role of human anti-chimeric antibodies (HACAs) by using radiolabelled infliximab. METHODS:Two responding and two non-responding patients with rheumatoid arthritis, infused with radiolabelled infliximab, were investigated by both imaging and serum analysis. RESULTS:Images showed predominant presence of infliximab in blood up to 24 h, with a trend of faster blood clearance and of higher liver/spleen uptake in a non-responding patient. Clinically inflamed joints showed uptake of the drug. The HACA level in the non-responders was high (1641 and 1008 U/ml), but low or not detectable in responders. Sucrose gradients of serum showed antibody complexes in both non-responders. Various sizes of antibody complexes, including very large ones, were observed in a non-responder who developed a serious infusion reaction. CONCLUSION:Formation of infliximab-anti-infliximab complexes were found in non-responders due to the presence of large amounts of HACA. This finding, supported by both imaging and serum analysis data, may explain failure of infliximab treatment.
journal_name
Ann Rheum Disjournal_title
Annals of the rheumatic diseasesauthors
van der Laken CJ,Voskuyl AE,Roos JC,Stigter van Walsum M,de Groot ER,Wolbink G,Dijkmans BA,Aarden LAdoi
10.1136/ard.2006.057406subject
Has Abstractpub_date
2007-02-01 00:00:00pages
253-6issue
2eissn
0003-4967issn
1468-2060pii
ard.2006.057406journal_volume
66pub_type
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journal_title:Annals of the rheumatic diseases
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doi:10.1136/ard.61.3.242
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journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
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更新日期:2018-11-01 00:00:00
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journal_title:Annals of the rheumatic diseases
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journal_title:Annals of the rheumatic diseases
pub_type: 临床试验,杂志文章,多中心研究
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更新日期:2004-01-01 00:00:00
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journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章,meta分析
doi:10.1136/annrheumdis-2017-212423
更新日期:2018-04-01 00:00:00
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journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章,多中心研究
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更新日期:2012-08-01 00:00:00
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pub_type: 杂志文章
doi:10.1136/ard.2004.029058
更新日期:2005-06-01 00:00:00
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journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/annrheumdis-2019-216137
更新日期:2020-02-01 00:00:00
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journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/annrheumdis-2013-204820
更新日期:2014-06-01 00:00:00
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journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/annrheumdis-2012-202781
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pub_type: 杂志文章
doi:10.1136/ard.60.4.427
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pub_type: 杂志文章
doi:10.1136/ard.37.1.30
更新日期:1978-02-01 00:00:00
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journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.60.6.550
更新日期:2001-06-01 00:00:00
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journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
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更新日期:2004-11-01 00:00:00
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journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.62.5.455
更新日期:2003-05-01 00:00:00
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journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.62.10.995
更新日期:2003-10-01 00:00:00
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journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.39.4.344
更新日期:1980-08-01 00:00:00
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journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章
doi:10.1136/ard.2003.012583
更新日期:2004-10-01 00:00:00
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journal_title:Annals of the rheumatic diseases
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1136/annrheumdis-2013-204195
更新日期:2015-03-01 00:00:00
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pub_type: 杂志文章,meta分析,评审
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更新日期:2017-07-01 00:00:00
abstract:BACKGROUND:Collagen-induced arthritis (CIA) is the most commonly used model of rheumatoid arthritis (RA). In both CIA and RA there is an increase in the cellular content of the synovium, this being dominated by macrophages. OBJECTIVE:To assess the impact of etoposide, a topoisomerase II antagonist known to induce mono...
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pub_type: 杂志文章
doi:10.1136/ard.61.9.829
更新日期:2002-09-01 00:00:00