Crohn’s disease study identifies genetic variant with potential to personalise treatment
The largest study ever to look at why an expensive and commonly used group of drugs fails some patients with Crohn's disease has identified a genetic marker which could individualise drug treatment.
A UK wide collaboration led by the University of Exeter, Royal Devon & Exeter NHS Foundation Trust and the Wellcome Sanger Institute, has demonstrated that a genetic variant carried by 40% of the population explains why some patients develop antibodies against the anti-TNF drugs, infliximab and adalimumab and lose response. The authors conclude that a further trial is required to confirm that genetic testing prior to treatment will reduce the rate of treatment failure by facilitating the most effective choice of therapy for individual patients.
Anti-tumour necrosis factor (TNF) drugs, infliximab and adalimumab, are used to treat patients with moderate to severe Crohn’s disease and ulcerative colitis when other treatments have not worked. Also known as biological medicines, these drugs work by blocking TNF, a protein which drives persistent gut inflammation. Introduced in the 1990s, anti-TNF drugs now rank in the top five by drug spend in the NHS.
Although anti-TNF drugs have given new hope for people with Crohn’s and Colitis, and provided an important treatment option, many patients lose response over time. One of the major reasons patients lose response is the development of an immune response to the drug (immunogenicity).
Anti-TNF drugs are large, complex molecules, made inside living cells. Repeated administration causes the immune system to recognise the drug as a potential threat rather than a medicine, leading to the production of antibodies against the drug. These antibodies increase the rate at which the drugs are removed from the body. As well as reducing the effectiveness of treatment, antibodies may also cause adverse drug reactions at the time of injection or infusion.
This research identified a genetic marker HLA-DQA1*05, carried by 40 per cent of the European population that increases risk of development of antibodies against infliximab and adalimumab 2-fold.
Helen Terry, Director of Research, Crohn’s and Colitis UK said: “The future of Crohn’s and Colitis treatment is personalised medicine, so the identification of a genetic marker that explains why anti-TNF drugs don’t work for some people with Crohn’s is highly significant. These results are extremely promising and with further research could lead to individualised treatment and better outcomes for the people living with these debilitating conditions.”
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