首页|Crohn's disease genotypes of patients in remission vs relapses after infliximab discontinuation

Crohn's disease genotypes of patients in remission vs relapses after infliximab discontinuation

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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 6infusions (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).

InfliximabAnti-tumor necrosis factor alphaCrohn's diseaseInflammatory bowel diseaseGenotype

Cathy Lu、Alistair Waugh、Robert J Bailey、Raeleen Cherry、Levinus A Dieleman、Leah Gramlich、Kata Matic

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Division of Gastroenterology, Zeidler Ledcor Center,University of Alberta, Edmonton, AB T6G 2X8, Canada

Division of Gastroenterology, Royal Alexandra Hospital, Edmonton, AB T5H 3V9, Canada

Division of Gastroenterology, Grey Nuns Hospital, Edmonton, AB T6L 5X8, Canada

2012

10.3748/wjg.v18.i36.5058

世界胃肠病学杂志(英文版)
太原消化病研治中心

世界胃肠病学杂志(英文版)

SCI
影响因子：1.001
ISSN：1007-9327
年,卷(期)：2012.18(36)
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