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

World Journal of Gastroenterology 2012年第36期18卷 5058-5064页

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 Division of Gastroenterology Zeidler Ledcor CenterUniversity of AlbertaEdmontonAB T6G 2X8Canada Division of Gastroenterology Royal Alexandra HospitalEdmontonAB T5H 3V9Canada Division of Gastroenterology Grey Nuns HospitalEdmontonAB T6L 5X8Canada Division of Gastroenterology Misericordia HospitalEdmontonAB T5R 4H5Canada

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, while two-thirds rel

关键词： Infliximab Anti-tumor necrosis factor alpha Crohn's disease Inflammatory bowel disease Genotype

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