The DNA Variants that can Predict Children’s IBD Treatment Response

Specific DNA variants are now known to be predictors of long-term response to antitumor necrosis factor (anti-TNF) drugs in children for treatment with Crohn’s disease or ulcerative colitis, types of inflammatory bowel disease (IBD), according to a paper published in the Journal of Pediatric Gastroenterology and Nutrition.

Investigators from Spain conducted a longitudinal cohort study of 209 children in order to study the long-term effects of anti-TNF drug treatment in children with IBD. The investigators also wanted to categorize anti-TNF treatment (specifically infliximab and adalimumab) failure by genotype.

The study authors said it is important to optimize IBD treatment in children because they have to live with the disease for much longer, and it is also more complex in this population. The children involved in the study were diagnosed with IBD and treated with anti-TNF drugs between 2016-2018.

The median age at diagnosis with IBD was 10.6 years, the study authors reported, and the median treatment initiation after diagnosis was 9.6 months. There were 31 patients who experienced clinical activity of IBD during the anti-TNF treatment, and time to treatment failure in these patients was a median of 15.2 months, the study authors learned.

Patients with Crohn’s disease or ulcerative colitis who failed anti-TNF treatment showed no significant differences in age at diagnosis, age at start of treatment, months from diagnosis to onset of therapy, sex, or other factors compared to those who did not fail treatment, the study authors said.

The investigators found 4 single-nucleotide polymorphisms (SNPs) associated with response to anti-TNF treatment among Crohn’s disease patients. One of these was predictive of a longer time to failure to treat with anti-TNF therapy, another two were predictive of a longer time to failure or better response to anti-TNF therapy, and the final one was also predictive of a longer-term response.

There was 1 SNP related to response among ulcerative colitis patients, which was associated with a longer-term response to anti-TNF treatment.

“These SNPs were not associated with the response to anti-TNF therapy in adults with Crohn’s disease,” corresponding study author Luis López-Fernández told HCPLive^(R). “This observation could improve our ability to adapt anti-TNF treatment in patients with IBD based on whether the disease takes the form of Crohn’s disease or ulcerative colitis.”

The study authors also found a previous study that examined adults with Crohn’s disease and response to anti-TNF with respect to the 4 related SNPs. However, the study authors said that there was no association between their findings and the response to anti-TNF treatment in adults related to the 4 SNPs. However, they believed this may be due to differences in the populations that limited comparisons between pediatric and adult data sets.

The study authors also noted that their sample size in this cohort did not allow them to categorize their results according to the type of treatment failure, whether it was immunogenic, pharmacokinetic, or pharmacodynamic.

“Our pediatric IBD cohort is one of the largest in the world, and the conclusions we reached could encourage other authors to validate the associations described here in other cohorts before application in clinical practice,” López-Fernández concluded.