title: Crohn's disease genotypes of patients in remission vs relapses after infliximab discontinuation.
abstract: OBJECTIVE
  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).
  
  
  CONCLUSIONS
  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.affiliation: Division of Gastroenterology, Zeidler Ledcor Center, University of Alberta, Edmonton, AB T6G 2X8, Canada.
authors.forename: Cathy
authors.initials: C
authors.lastname: Lu
authors.forename: Alistair
authors.initials: A
authors.lastname: Waugh
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Bailey
authors.forename: Raeleen
authors.initials: R
authors.lastname: Cherry
authors.forename: Levinus A
authors.initials: LA
authors.lastname: Dieleman
authors.forename: Leah
authors.initials: L
authors.lastname: Gramlich
authors.forename: Kata
authors.initials: K
authors.lastname: Matic
authors.forename: Mario
authors.initials: M
authors.lastname: Millan
authors.forename: Karen I
authors.initials: KI
authors.lastname: Kroeker
authors.forename: Daniel
authors.initials: D
authors.lastname: Sadowski
authors.forename: Christopher W
authors.initials: CW
authors.lastname: Teshima
authors.forename: Dennis
authors.initials: D
authors.lastname: Todoruk
authors.forename: Clarence
authors.initials: C
authors.lastname: Wong
authors.forename: Karen
authors.initials: K
authors.lastname: Wong
authors.forename: Richard N
authors.initials: RN
authors.lastname: Fedorak
mesh_terms: D000293:Adolescent; D000328:Adult; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D003424:Crohn Disease / Q000188:drug therapy / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D000069285:Infliximab; D008297:Male; D008875:Middle Aged; D053473:Nod2 Signaling Adaptor Protein / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012008:Recurrence; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
chemical_list: D000911:Antibodies, Monoclonal; C429018:NOD2 protein, human; D053473:Nod2 Signaling Adaptor Protein; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab