Document Detail

Impact of antibodies to infliximab on clinical outcomes and serum infliximab levels in patients with inflammatory bowel disease (IBD): a meta-analysis.
MedLine Citation:
PMID:  23147525     Owner:  NLM     Status:  MEDLINE    
OBJECTIVES: Antibodies to infliximab (ATIs) have been associated with loss of clinical response and lower serum infliximab (IFX) levels in some studies of patients with inflammatory bowel disease (IBD). This has important implications for patient management and development of novel biologic therapies. The objective of this study was to perform a systematic review and meta-analysis of studies that reported clinical outcomes and IFX levels according to patients' ATI status.
METHODS: MEDLINE, Web of Science, CINAHL, Scopus, and EMBASE were searched for eligible studies. Quality assessment was undertaken using GRADE (Grading of Recommendations Assessment, Development and Evaluation) criteria. Raw data from studies meeting inclusion criteria was pooled for meta-analysis of effect estimates. Sensitivity analysis was performed for all outcomes. Funnel plot was performed to assess for publication bias.
RESULTS: Thirteen studies met the inclusion criteria, and reported results in 1,378 patients with IBD. All included studies had a high risk of bias in at least one quality domain. The pooled risk ratio (RR) of loss of clinical response to IFX in patients with IBD who had ATIs was 3.2 (95% confidence interval (CI): 2.0-4.9, P<0.0001), when compared with patients without ATIs. This effect estimate was predominantly based on data from patients (N=494) with Crohn's disease (RR: 3.2, 95% CI: 1.9-5.5, P<0.0001). Data only from patients with ulcerative colitis (n=86) exhibited a non-significant RR of loss of response of 2.2 (95% CI: 0.5-9.0, P=0.3) in those with ATIs. Heterogeneity existed between studies, in both methods of ATI detection, and clinical outcomes reported. Three studies (n=243) reported trough serum IFX levels according to ATI status; the standardized mean difference in trough serum IFX levels between groups was -0.8 (95% CI -1.2, -0.4, P<0.0001). A funnel plot suggested the presence of publication bias.
CONCLUSIONS: The presence of ATIs is associated with a significantly higher risk of loss of clinical response to IFX and lower serum IFX levels in patients with IBD. Published studies on this topic lack uniform reporting of outcomes. High risk of bias was present in all the included studies.
Kavinderjit S Nanda; Adam S Cheifetz; Alan C Moss
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Publication Detail:
Type:  Journal Article; Meta-Analysis; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Review     Date:  2012-11-13
Journal Detail:
Title:  The American journal of gastroenterology     Volume:  108     ISSN:  1572-0241     ISO Abbreviation:  Am. J. Gastroenterol.     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-01-04     Completed Date:  2013-02-27     Revised Date:  2014-04-08    
Medline Journal Info:
Nlm Unique ID:  0421030     Medline TA:  Am J Gastroenterol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  40-7; quiz 48     Citation Subset:  IM    
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MeSH Terms
Anti-Inflammatory Agents, Non-Steroidal / blood,  immunology*,  pharmacokinetics,  therapeutic use
Antibodies, Anti-Idiotypic / blood*
Antibodies, Monoclonal / blood,  immunology*,  pharmacokinetics,  therapeutic use
Biological Markers / blood
Inflammatory Bowel Diseases / blood,  drug therapy*,  immunology
Maintenance Chemotherapy
Treatment Failure
Grant Support
Reg. No./Substance:
0/Anti-Inflammatory Agents, Non-Steroidal; 0/Antibodies, Anti-Idiotypic; 0/Antibodies, Monoclonal; 0/Biological Markers; 0/anti-IgG; 0/infliximab

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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