The effects of NOD2 genotype, smoking and immunomodulators on postoperative recurrence of ileal Crohnʼs disease

Abstract

Background and AimS: Crohn's disease (CD) most commonly affects the terminalileum and most patients require one or more ileocolic resections (ICR) duringthe disease course. We have been studying factors, such as genotype, and environmentthat influence time to repeat surgery in an ileal CD cohort. Our aim wasto determine how NOD2 genotype affects surgical complications of ileocolicresection and the time to second resection in ileal CD patients. Methods: Survival analyses were used to assess the effect of genotype (NOD2, ATG16L1) in addition to phenotype and post-operative prescription of medications, on the time to second ICR in 285 ileal CD patients who underwent ICR astheir initial surgery. Results: Forty one percent of the patients harbored at least one of the threemajor NOD2 risk variants (Leu1007fs, R702W and G908R, NOD2R) and 59% harborednone of the three risk alleles, NOD2NR. Thirty six percent of patients werehomozygous for the ATG16L1 T300A risk allele, 46% were heterozygous and 18%were homozygous for the non-risk allele. The median age of diagnosis was lowerin NOD2R compared to NOD2NR patients, (24, range 7-59 years vs. 27, range 9-71years, P = 0.027). There was a trend towards a younger median age of surgery inNOD2R compared with NOD2NR patients (27, range 2-61years vs.32, range 10-75years, P = 0.053), but no difference in the median duration of disease prior toinitial ICR (2, range 0-25y vs. 3, range 0-38 y, P = 0.31). Univariate analyses confirmedthe findings of a previous analysis that smoking at the time of initial ICRwas associated with a reduced time to second ICR (6.2 vs. 7 years, P = 0.049) andprescription of post-operative immunomodulators was associated with an increasedmedian time to second ICR (6 vs 8 years, P = 0.019). The Cox proportional hazardsmodel with stepwise variable selection found that postoperative prescription ofimmunomodulators was associated with a decreased risk of a second ileocolicresection (hazard ratio 0.67, 95 percent confidence interval 0.47-0.96, P= 0.028). Conclusions: Postoperative prescription of immunomodulators is associatedwith a reduced risk of surgical recurrence. NOD2 genotype may be associatedwith earlier age of surgery due to its association with earlier age of diagnosis.