Variation in Single Gene May Determine Response to Humira in IBD Patients, Study Reports

Variation in Single Gene May Determine Response to Humira in IBD Patients, Study Reports

A single variation in the DNA sequence of a particular gene, called ATG16L1, was associated with response to Humira (adalimumab) treatment in a group of people with inflammatory bowel disease (IBD), a disease in which genetics is known to play a role and newer therapies have had a somewhat mixed response.

Humira, with Remicade (infliximab), is an anti-tumor necrosis factor-alpha (anti-TNFα) known to be capable of inducing and maintaining remission in certain IBD cases, but “are not effective in 20–40% of IBD patients and loss of response and/or is seen in a substantial proportion of the patients,” the researchers wrote.

Their study “Genetic polymorphism in ATG16L1 gene is associated with adalimumab use in inflammatory bowel disease,” published in the Journal of Translational Medicine, investigated possible reasons for this, and if findings might support better personalized treatment.

Single nucleotide polymorphisms (SNPs) are a single natural variation in the DNA, where one nucleotide (building block) is changed. Recent genome-wide studies have identified more than 163 SNPs that associate with IBD.

Researchers in Rotterdam evaluated whether the genetic profile of IBD patients, including IBD-associated SNPs, were able to predict patient response to anti-TNFα treatment, such as Remicade and Humira.

They analyzed DNA samples from 570 patients at the Erasmus MC University Medical Center: Crohn’s disease was present in 71.9% (411 patients), ulcerative colitis in 26% (148 patients), and unclassified IBD in 1.9% (11 patients).

Most patients were using either Remicade (211 patients) or Humira (179 patients) as therapy, or a combination of Remicade and Humira (111 patients). The team evaluated patients’ response and loss of response to treatment, as well as side effects.

The analysis included SNPs in nine IBD related genes – the IRGM, ATG16L1, NOD2, XBP1, LRRK2, IL23R, CCR6, STAT3 and NCF4.

“The only significant association between anti-TNF alpha use and genetic risk variants was found for ATG16L1,” the researchers wrote.

IBD and CD patients carrying the SNP — referred to as rs10210302 — in the ATG16L1 gene were more likely to be treated with Humira, even after researchers adjusted the results for patients’ age and disease phenotype and behavior. No association was found for the SNP and the use of Remicade.

Previous results have shown that variants in the ATG16L1 gene strongly associate with IBD incidence. These variants may affect the process by which immune cells clear bacteria, leading to an imbalance of the bacterial burden in patients with IBD.

Overall, “genetic polymorphisms in the ATG16L1 gene correlate with ADA [adalimumab] treatment, for which a previously unidentified disease phenotype may be responsible,” the scientists wrote.

These findings suggest that “genetic make-up of IBD patients may in future help physicians decide on personalized treatment strategies,” the study concluded, recommending further research into these findings.

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