Mucosal IL13RA2 expression predicts nonresponse to anti‐TNF therapy in Crohn's disease

Summary Background Ileocolonic expression of IL13RA2 has been identified as a predictive marker for nonresponsiveness to infliximab (IFX) in patients with Crohn's disease (CD). Aim To validate the IL13RA2 biomarker, study its anti‐TNF specificity and get a better understanding of the underlying biology driving its expression. Methods IL13RA2 mucosal expression was studied in a cohort of adalimumab and vedolizumab treated patients. To identify the upstream regulators of anti‐TNF nonresponsiveness, weighted gene co‐expression network analysis was applied on publicly available microarray data of IFX‐treated patients. Selected serum proteins, including TNF, were measured prior to first IFX exposure and compared between healers and nonhealers. Results Increased mucosal IL13RA2 expression prior to start of biological therapy was predictive for anti‐TNF nonresponsiveness specifically (AUROC, area under the curve = 0.90, P