Mucosal Gene Signatures

Infliximab (IFX) is effective treatment for Crohn's disease (CD) and ulcerative colitis (UC) not responding to standard therapy. 30-40% of patients do not improve and response is often incomplete. The aim of this study is to identify mucosal gene signatures predictive of response to EFX using high-density oligonucleotide arrays. Eight UC patients and 12 CD patients showed healing. In UC, only one probe set was differentially expressed in responders compared with non-responders, ie IL-13Ralpha2. At PAM analysis 2 probe sets, representing IL-13Ralpha2 and IL-I l, separated IBD responders from non-responders with an overall misclassification error rate of 0.046 (2/43), with 100% sensitivity and 91.3 % specificity. The IL-13Ralpha2 probe set was a top-ranked probe set in all our analyses using both LIMMA and PAM strategies.; Our gene array studies of mucosal biopsies identified IL-13Ralpha2 in IBD as a predictor of (non-)response to IFX.

WO 2,009,117,791


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