Scientists have identified a genetic variant carried by 40% of the population that may explain why TNF treatments for Crohn’s Disease fail for some patients. The ground-breaking study marks further progress toward a personalised approach to the diagnosis and treatment of this debilitating condition.
Anti-tumour necrosis factor (TNF) drugs are prescribed to patients with severe Crohn’s disease and ulcerative colitis when other drugs haven’t worked. The drugs work by blocking a protein called TNF, which causes inflammation of the gut. It’s widely prescribed, but over time it becomes less effective. After repeated use, the body’s immune system sees the medication as a threat and produces antibodies to target the drug. These antibodies reduce the positive impact of the drug, causing symptoms to worsen.
During the Personalised anti-TNF therapy in Crohn’s disease study (PANTS), scientists examined the clinical data and genetic information of 1,240 from 120 hospitals to search for an explanation – and they’ve found one. Researchers were able to identify a genetic marker called HLA-DQA1*05 that doubles the risk of developing antibodies against infliximab and adalimumab.
The researchers hope that by identifying the gene responsible for the reduced response, they can develop more effective treatments for each patient. If patients have the gene for example, they may be prescribed alternative medication with a higher chance of success.
“The future of Crohn’s and Colitis treatment is personalised medicine,” said Helen Terry, Director of Research, Crohn’s and Colitis UK. “The identification of a genetic marker that explains why anti-TNF drugs don’t work for some people with Crohn’s is highly significant.”
The study provides exciting avenues for future studies, Terry believes. “Further research could lead to individualised treatment and better outcomes for the people living with these debilitating conditions.”
Researchers are making rapid progress in identifying the causes of Crohn’s disease, including the vital role our genes play. They’re being supported by innovative research collaborations, such as the IBD BioResource, an open-access platform that gives researchers genetic information on 25,000 patients, including serum, plasma and DNA sample, and genetic profiling.
Current treatments for Crohn’s Disease are typically made with a “one-size-fits-all approach,” conclude scientists writing in The Lancet Gastroenterology & Hepatology.
However, positive work such as the PANTS study gives scientists a greater understanding of the biological mechanisms at work. “These disease mechanisms can be used to develop clinically useful biomarkers, identify novel approaches to optimise disease control, and help deliver the goal of personalised medicine,” the authors believe.
One of the most important recent developments is the establishment of a link between mutations in the ATG16L1, IL23R, IRGM, and NOD2 genes and an increased risk of developing Crohn’s Disease. By identifying these mutations, patients can understand their risk of developing Crohn’s Disease.
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Our SNPs test uses your DNA to assess how you would respond to treatment with standard medications, including anti-inflammatories, antibiotics and anticoagulants.
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You can read the study, HLA-DQA1*05 Carriage Associated With Development of Anti-Drug Antibodies to Infliximab and Adalimumab in Patients With Crohn’s Disease, here.
You can read the paper, Personalised medicine in Crohn’s disease, here.
