Gene Signatures of Early Response to Anti-TNF Drugs in Pediatric Inflammatory Bowel Disease

Around a 20-30% of inflammatory bowel disease (IBD) patients are diagnosed before they are 18 years old. Anti-TNF drugs can induce and maintain remission in IBD, however, up to 30% of patients do not respond. The aim of the work was to identify markers that would predict an early response to anti-TNF drugs in pediatric patients with IBD. The study population included 43 patients aged <18 years with IBD who started treatment with infliximab or adalimumab. Patients were classified into primary responders ( = 27) and non-responders to anti-TNF therapy ( = 6). Response to treatment could not be analyzed in 10 patients. Response was defined as a decrease in over 15 points in the disease activity indexes from week 0 to week 10 of infliximab treatment or from week 0 to week 26 of adalimumab treatment. The expression profiles of nine genes in total RNA isolated from the whole-blood of pediatric IBD patients taken before biologic administration and after 2 weeks were analyzed using qPCR and the 2 method. Before initiation and after 2 weeks of treatment the expression of was decreased in patients who were considered as non-responders ( value < 0.05). Changes in expression were also observed for at T0 and T2, although that did not reach the level of statistical significance. In addition, the expression of decreased 1.75-fold during the first 2 weeks of anti-TNF treatment in responders, whereas no changes were observed in non-responders. Expression of the gene is a pharmacogenomic biomarker of early response to anti-TNF agents in pediatric IBD. and need to be validated in larger studies.

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