Mechanisms in failure of infliximab for Crohn's disease

Expression of tumour necrosis factor-α (TNF-α) is increased in patients with Crohn's disease. Nuclear factor kappa B (NFκB) controls transcription of inflammation genes. Treatment with monoclonal antibodies to TNF (infliximab) in refractory Crohn's disease results in a remission rate of 30...

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Bibliographic Details
Published in:The Lancet (British edition) 2000-10, Vol.356 (9240), p.1475-1479
Main Authors: Nikolaus, Susanna, Raedler, Andreas, Kühbacher, Tanja, Sfikas, Nicolaos, Fölsch, Ulrich R, Schreiber, Stefan
Format: Article
Language:English
Subjects:
Activation
Antibodies, Monoclonal - therapeutic use
Biological and medical sciences
Biopsy
Bowel disease
Cell Nucleus - chemistry
Cell Nucleus - drug effects
Clinical trials
Colon
Crohn Disease - drug therapy
Crohn's disease
Cytokines
Digestive system
Disease control
Drug dosages
Endoscopy
Failure mechanisms
Genes
Humans
Immune system
Immunoassay
Immunology
Immunotherapy
Inflammation
Inflammatory bowel disease
Inflammatory bowel diseases
Infliximab
Medical sciences
Monoclonal antibodies
Mucosal immunity
NF-kappa B - drug effects
NF-kappa B - metabolism
NF-κB protein
Patients
Pharmacology. Drug treatments
Proteins
Remission
Steroids
Time Factors
Transcription
Transcription Factor RelA
Treatment Outcome
Tumor Necrosis Factor-alpha - antagonists & inhibitors
Tumor Necrosis Factor-alpha - immunology
Tumor necrosis factor-TNF
Tumor necrosis factor-α
Tumors
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Summary:Expression of tumour necrosis factor-α (TNF-α) is increased in patients with Crohn's disease. Nuclear factor kappa B (NFκB) controls transcription of inflammation genes. Treatment with monoclonal antibodies to TNF (infliximab) in refractory Crohn's disease results in a remission rate of 30–50% after 4 weeks. We aimed to assess the clinical and immunological mechanism of failure to respond to infliximab. 24 patients with steroid refractory, chronic active Crohn's disease (Crohn's disease activity index [CDAI]>200), who showed an inflammatory manifestation in the sigmoid colon, had a single infusion of infliximab (5 mg/kg bodyweight) and were followed up for 16 weeks. Secretion capacity for TNF-α was assessed in whole-blood cytokine assays and nuclear concentrations of NFκB p65 were determined in colonic mucosal biopsy samples. 21 (88%) of 24 patients were in remission (CDAI
ISSN:0140-6736
1474-547X
DOI:10.1016/S0140-6736(00)02871-3