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News — A study from Michigan Medicine researchers has investigated possible genetic factors for drug efficacy for children with Crohn’s disease.

The resulting paper, “” appeared in the American Journal of Gastroenterology.

Previous studies of adults with Crohn’s disease had found that the allele HLA-DQA1*05 was associated with developing anti-drug antibodies to a group of medicines known as tumor necrosis factor antagonists (anti-TNF).

These anti-inflammatory drugs, including infliximab and adalimumab, are a mainstay of treatment for Crohn’s Disease.

For many pediatric patients prescribed anti-TNF medicines, the drugs stop working, resulting in about . 

This is a serious problem since while there are other few medications approved for treating adults, no other medicines are approved for children with Crohn’s disease.

In this latest study, HLA DQA1*05 positive children just taking the anti-TNF mediation had the highest rate of drug failure.

Children without the genetic marker—and who were also taking methotrexate—had the lowest rate of drug failure and anti-drug antibody development.

“The big issue in pediatric Crohn’s Disease is that it’s a lifelong disease,” said Jeremy Adler, M.D., M.Sc., U-M clinical professor of Pediatrics and lead author on the paper.

“We don't have a cure. So that's why drug persistence is one of the main things we looked at. We want the drug to work and to keep working.”

When anti-TNF medicines stop working in children with Crohn’s disease, physicians weigh various options: increasing the dose, adding methotrexate, or using other medicines such as more expensive off-label medicines approved only for adults with Crohn’s disease.

Introducing methotrexate carries some risks, as the child’s immune system becomes further suppressed. Researchers hope a further investigation of why drugs stop working will help physicians as they navigate these decisions.

This research utilized existing blood samples from a previous multi-center,  conducted by the same group, which compared the efficacy of patients taking anti-TNF medications on their own to taking them in combination with methotrexate. The initial results of the trial, published in 2023, showed that the combined therapy led to a two-fold reduction in treatment failure.

In this trial, 43% of patients were HLA DQ-A1*05 positive, and 30% experienced treatment failure. HLA DQ-A1*05 positive children were twice as likely to develop antidrug antibodies, though the results were not statistically significant. 

Still, Adler hopes one day a blood screen for this genetic marker will be a standard part of treating children with Crohn’s Disease. 

“I’m not testing everybody yet,” said Adler. “But if somebody has developed anti-drug antibodies, or I need to escalate the dose, or they've already had reactions—those are the people I'm checking.” 

HLA DQ-A1*05 can help planning next steps for treatment escalation, combination therapy, or switching to a second anti-TNF medication.