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CROHN'S DISEASE GENOTYPE IS SIMILAR BETWEEN PATIENTS WHO SUSTAIN A LONG-TERM REMISSION AND THOSE WHO RAPIDLY RELAPSE AFTER DISCONTINUING INFLIXIMAB
C Lu1, A Waugh1, R Bailey2, R Cherry3, L Dieleman1, L Gramlich2, K Matic2, M Millan3, K Kroeker1, D Sadowski2, C Teshima1, D Todoruk2, C Wong2, K Wong1, R Fedorak11Center of Excellence for Gastrointestinal Inflammation and Immunity Research, Division of Gastroenterology; 2Royal Alexandra Hospital; 3Misericordia Hospital, University of Alberta, Edmonton, AB
Aims: The majority of patients with Crohn's disease (CD) who have obtained an infliximab-induced clinical remission will relapse after their anti-TNFalpha (tumor necrosis factor) therapy has been discontinued. Interestingly, factors such as concomitant drug therapy, age, gender, and disease location do not affect the duration of remission. This finding lends support to the hypothesis that a patient-unique genotype of CD may play a role in determining the duration of long-term remission after the discontinuation of anti-TNFalpha agent therapy. We aimed to compare genetic differences (IBD5, NOD2/CARD 15) between CD patients who experienced a sustained corticosteroid-free clinical remission after discontinuing infliximab to those patients who relapsed over a period of up to 10 years.
Methods: Genetic analyses were performed on 14 CD patients (six remission, eight non-remission) identified from a longitudinal cohort study from a university-based IBD referral center. All of these patients had obtained full clinical remission and had discontinued infliximab for reasons other than loss of response.
Results: 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 the CD patients who relapsed early or in the patients who remained in extended remission following the discontinuation of infliximab. Of the genetic variants analyzed, there was no significant higher chance of disease relapse compared to the patients without mutation in the study population.
Conclusions: In a cohort of infliximab-treated CD patients who respond with a sustained corticosteroid-free clinical remission and then discontinued infliximab, the NOD2 and IBD5 polymorphisms are similar between the two subgroups; those who relapse early and those who have an extended remission. This study was the first to attempt to identify genetic polymorphisms in these two subgroups. The potential role of IBD5 and NOD2/CARD15 mutations in predicting remission response rates with infliximab and the duration of such therapy to maintain remission in CD remains elusive. However, the possibility of a genetic explanation for varying patient responses to anti-TNFalpha remains high.