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

作　　者：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 

机构地区：[1]Division of Gastroenterology,Zeidler Ledcor Center,University of Alberta,Edmonton,AB T6G 2X8,Canada [2]Division of Gastroenterology,Royal Alexandra Hospital,Edmonton,AB T5H 3V9,Canada [3]Division of Gastroenterology,Grey Nuns Hospital,Edmonton,AB T6L 5X8,Canada [4]Division of Gastroenterology,Misericordia Hospital,Edmonton,AB T5R 4H5,Canada

出　　处：《World Journal of Gastroenterology》2012年第36期5058-5064,共7页世界胃肠病学杂志（英文版）

基　　金：Supported by Center of Excellence for Gastrointestinal,Inflammation and Immunity Research at the University of Alberta

摘　　要：AIM： To investigate genetic differences between Crohn＇s disease （CD） patients with a sustained remission vs relapsers after discontinuing infliximab while in cortico- steroid-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 remis- sion was defined as corticosteroid-free plus normaliza- tion 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 thera- peutic intervention with CD medication（s）, or a hospital- ization 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 do- main 15 （CARD15） polymorphisms （R702W, G908R and L1007fs） and the inflammatory bowel disease 5 （IBDS） polymorphisms （IGR2060a1 and IGR3081a1） were ana- lyzed in each group. RESULTS： Five single nucleotide polymorphisms of IBD5 and NOD2/CARD15 genes were successfully analyzed for all 14 subjects. There was no signifcant increase in frequency of the NOD2/CARD15 polymor- phisms （R702W, G908R and L1007fs） and the IBD5 polymorphisms （IGR2060al and IGR3081a1） in either group of patients; those whose disease relapsed rap- idly 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 re- sponse remained in sustained clinical remission, whilAIM: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 discon

关 键 词：INFLIXIMAB Anti-tumor necrosis factor alpha Crohn＇s disease Inflammatory bowel disease GENOTYPE 

分 类 号：R574.62[医药卫生—消化系统]