Genotyping DNA variants before starting treatment in pediatric patients with inflammatory bowel disease (IBD) may help identify long-term responders to anti-tumor necrosis factor (anti-TNF) therapy and foster more personalized treatment, according to results from an observational, longitudinal, ambispective study published in the Journal of Pediatric Gastroenterology and Nutrition.
Researchers identified a cohort of 209 children with an IBD diagnosis from 17 pediatric IBD units in Spain between 2016 and December 2018. To be included in the study, patients had to be younger than18 years, diagnosed with Crohn disease (CD) or ulcerative colitis (UC), and have been previously treated with infliximab or adalimumab. Patients in treatment with either drug during recruitment were also included in the analysis.
In patients with CD (n=147), clinical remission was defined as a weighted Pediatric Crohn Disease Activity Index <12.5 points, and a response was defined as a >17.5 point change from the initial index. For patients with UC (n=62), remission was identified as a Pediatric Ulcerative Colitis Activity Index <10 points, with a response defined as a change of ≥20 points. Blood samples were collected for the analyses and investigators genotyped 21 single nucleotide polymorphisms (SNPs) that were previously studied in adults with CD using a real time polymerase chain reaction system. Using a log rank test, researchers analyzed the association of SNPs and time to failure of treatment.
While the findings for all other variables were similar for pediatric patients with UC and CD, patients with UC showed significant differences in anti-TNF treatment (P =.007) and response rate (P =.006) when compared with patients with CD. Moreover, investigators identified 3 SNPs in IL10, IL17A, and IL6 that were significantly associated with long term response to anti-TNF treatment in patients diagnosed with CD (rs1800872-HR, 4.749 [95%CI, 1.156-19.517], P <.031; rs2275913-HR, 0.320 [95%CI, 0.111-0.920], P <.034; and rs10499563-HR, 0.210 [95%CI, 0.047-0.947], P =.042, respectively). Among pediatric patients diagnosed with UC, one SNP in LY96 was significantly associated with long term response to anti-TNF treatment (rs-11465996-HR, 10.220 [95%CI, 1.849-56.504]; P <.05).
One limitation of this study was its small sample size. Although this cohort of pediatric patients with IBD “is one of the largest in the world,” it did not allow researchers to stratify their results according to the type of treatment failure. Moreover, there was a lower than expected rate of failure of anti-TNF treatment, and the Hardy-Weinberg equilibrium was not attained for r21800872 and r210499563.
Investigators noted, “This observation could improve our ability to adapt anti-TNF treatment in patients with pediatric IBD based on whether the disease takes the form of CD or UC.”
Salvador-Martín S, Bossacoma F, Pujol-Muncunill D, et al. Genetic predictors of long-term response to anti-TNF agents in pediatric inflammatory bowel disease. J Pediatr Gastroenterol Nutr. Published online August 5, 2020. doi:10.1097/MPG.0000000000002840