Johns, E.; Ahmad, T.; Hubbard, R.; Jewell, D.P.; Travis, S.P.L.
April 2003
Gut;Apr2003 Supplement 1, Vol. 52, pA12
Academic Journal
Introduction: There is a need to be able to identify patients at highest risk of relapse after surgery for Crohn's disease, so that preventative treatment can be targeted at those most likely to benefit. Combining clinical risk factors and genotype to predict risk has not previously been explored. Methods: All 105 patients who had had surgery for ileocaecal Crohn's disease at the John Radcliffe Hospital, Oxford, on whom DNA had been collected and follow up data obtained were selected. Three endpoints were defined duration of steroid free remission (EP1), time to clinical relapse (EP2), and t me to surgical relapse (FP3). Forty one clinical and 57 genetic variables were recorded. Multivariate analysis was performed using the Accelerated Life Model, before decision tree analysis to identify prognostic groups. Owing to the large number of variables, genotypic analysis focused on three mutations of the NOD2 gene and 10 other genes in the HLA region on chromosome 6. Results: Mean follow up duration was 175 months (range 6-840). Median time (range) to EP1 was 56 (0-540) months; to EP2, 74 (0-810) months; and to EP3, 120 (3-810) months. Perianal disease at index surgery and retinoid X receptor beta 1 genotype were the only variables associated with shorter times (all p < 0.0004) and heat shock protein 1 genotype with longer times to all three endpoints (p = 0.0145, p < 0.0001 p < 0.0001). Smoking and IkB14 genotype predicted a shorter duration of steroid free remission and time to further surgery, while age > 40 year, male sex, and NOD3020 genotype predicted a longer duration. Decision tree analysis only predicted steroid free remission: if transmembrane receptor notch 4 genotype positive (n = 80), 60% require steroids within 5 years, compared with 24% if notch 4 negative. Conclusions: Smoking and perianal disease are confirmed as predictors of a higher relapse rate after surgery. Genotypes associated with a higher relapse rate are different to those currently...


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