Tissue markers may predict treatment response to antitumor necrosis factor‐α agents in children with Crohn's disease

Abstract

AbstractObjectivesPatients with moderate‐severe Crohn's disease (CD) who are treated with antitumor necrosis factor alpha (TNF‐α) agents may be subjected to primary nonresponse or partial response. We aimed to identify tissue markers that may predict response to these agents.MethodsPediatric patients (6–18 years) with either ileal or ileo‐colonic CD who were treated with anti‐TNF‐α were stratified into three different groups based on their overall response to therapy at the end of induction including clinical and laboratory parameters (group 1—full responders [FR], group 2—partial responders [PR], group 3—nonresponders [NR]). Seven tissue markers (fibronectin, interleukin [IL]‐23R, IL‐23, TNF‐α, collagen‐III, IL‐13R, and hypoxia‐inducible factors [HIF]‐1α) were evaluated. Immunofluorescence (IF) analyses were performed on biopsies from the terminal ileum, which were retrieved up to 6 months before treatment initiation.ResultsTwenty‐six CD patients (16 [61.5%] males; age 13.9 ± 2.9 years), including 8 (30.8%) with ileal disease and 18 (69.2%) with ileo‐colonic disease, were enrolled. Terminal ileum biopsies from nine patients from group 1, nine from group 2, and eight from group 3 were evaluated. Three antibodies were found to be significantly different between NR and FR groups; Collagen III and fibronectin stains were significantly more prominent in NR patients, while TNF‐α stain was significantly more pronounced in FR, p < 0.05 for each. PR could not have been predicted with neither of markers.ConclusionsDecreased tissue IF intensity of fibronectin and collagen III and increased intensity of TNF‐α may predict response to anti‐TNF‐α treatment.