Document Detail


Crohn's disease genotypes of patients in remission vs relapses after infliximab discontinuation.
MedLine Citation:
PMID:  23049214     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
AIM: To investigate genetic differences between Crohn's disease (CD) patients with a sustained remission vs relapsers after discontinuing infliximab while in corticosteroid-free remission.
METHODS: Forty-eight CD patients received infliximab and were in full corticosteroid-free clinical remission but then discontinued infliximab for reasons other than a loss of response, were identified by review of an electronic database and charts. Infliximab-associated remission was defined as corticosteroid-free plus normalization of clinical disease activity [CD activity index (CDAI) < 150] during follow-up visits based on physician global assessments. A CD relapse (loss of infliximab-induced remission) was clinically defined as a physician visit for symptoms of disease activity (CDAI > 220) and a therapeutic intervention with CD medication(s), or a hospitalization with complications related to active CD. Genetic analyses were performed on samples from 14 patients (n = 6 who had a sustained long term remission after stopping infliximab, n = 8 who rapidly relapsed after stopping infliximab). Nucleotide-binding oligomerization domain 2 (NOD2)/caspase activation recruitment domain 15 (CARD15) polymorphisms (R702W, G908R and L1007fs) and the inflammatory bowel disease 5 (IBD5) polymorphisms (IGR2060a1 and IGR3081a1) were analyzed in each group.
RESULTS: Five single nucleotide polymorphisms of IBD5 and NOD2/CARD15 genes were successfully analyzed for all 14 subjects. There was no significant increase in frequency of the NOD2/CARD15 polymorphisms (R702W, G908R and L1007fs) and the IBD5 polymorphisms (IGR2060a1 and IGR3081a1) in either group of patients; those whose disease relapsed rapidly or those who remained in sustained long term remission following the discontinuation of infliximab. Nearly a third of patients in full clinical remission who stopped infliximab for reasons other than loss of response remained in sustained clinical remission, while two-thirds relapsed rapidly. There was a marked difference in the duration of clinical remission following discontinuance of infliximab between the two groups. The patients who lost remission did so after 1.0 years ± 0.6 years, while those still in remission were at the time of this study, 8.1 years ± 2.6 years post-discontinuation of infliximab, P < 0.001. The 8 patients who had lost remission after discontinuing infliximab had a mean number of 5 infusions (range 3-7), with a mean treatment time of 7.2 mo (range 1.5 mo-15 mo). The mean duration of time from the last infusion of infliximab to the time of loss of remission was 382 d (range 20 d-701 d). The 6 patients who remained in remission after discontinuing infliximab had a mean number of 6 infusions (range 3-12), with a mean treatment duration of 12 mo (range 3.6 mo-32 mo) (P = 0.45 relative to those who lost remission).
CONCLUSION: There are no IBD5 or NOD2/CARD15 mutations that predict which patients might have sustained remission and which will relapse rapidly after stopping infliximab.
Authors:
Cathy Lu; Alistair Waugh; Robert J Bailey; Raeleen Cherry; Levinus A Dieleman; Leah Gramlich; Kata Matic; Mario Millan; Karen I Kroeker; Daniel Sadowski; Christopher W Teshima; Dennis Todoruk; Clarence Wong; Karen Wong; Richard N Fedorak
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  World journal of gastroenterology : WJG     Volume:  18     ISSN:  2219-2840     ISO Abbreviation:  World J. Gastroenterol.     Publication Date:  2012 Sep 
Date Detail:
Created Date:  2012-10-10     Completed Date:  2013-05-03     Revised Date:  2014-05-20    
Medline Journal Info:
Nlm Unique ID:  100883448     Medline TA:  World J Gastroenterol     Country:  China    
Other Details:
Languages:  eng     Pagination:  5058-64     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Adolescent
Adult
Antibodies, Monoclonal / therapeutic use*
Crohn Disease / drug therapy,  genetics*
Female
Genotype
Humans
Male
Middle Aged
Nod2 Signaling Adaptor Protein / genetics*
Polymorphism, Single Nucleotide*
Recurrence
Tumor Necrosis Factor-alpha / antagonists & inhibitors*
Chemical
Reg. No./Substance:
0/Antibodies, Monoclonal; 0/NOD2 protein, human; 0/Nod2 Signaling Adaptor Protein; 0/Tumor Necrosis Factor-alpha; 0/infliximab
Comments/Corrections

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