Infliximab (IFX) has become the mainstay of therapy of refractory Crohn's disease (CD). However, a subset of patients shows incomplete or no response to this agent. In this study we investigated whether we could identify a mucosal gene panel to predict response to IFX in CD.
Mucosal biopsies were obtained during endoscopy from 37 patients with active CD (19 Crohn's colitis [CDc] and 18 Crohn's ileitis [CDi]) before and after first IFX treatment. Response was defined based on endoscopic and histologic findings. Total RNA was analyzed with Affymetrix U133 Plus 2.0 Arrays. Quantitative RT-PCR was used to confirm microarray data.
At baseline, significant gene expression differences were found between CDc and CDi. For predicting response in CDc, comparative analysis of CDc pretreatment expression profiles identified 697 significant probe sets between CDc responders and CDc nonresponders. Class prediction analysis of CDc top 20 and top 5 significant genes allowed complete separation between CDc responders and CDc nonresponders. The CDc top 5 genes were TNFAIP6, S100A8, IL11, G0S2, and S100A9.
This study identified a 100% accurate predictive gene signature for response to IFX in CDc, whereas no predictive gene set could be identified for CDi.