Study: Genetic Variant Leads to Antibody Response in Patients with Crohn Disease

The largest study of its kind has found that 40% of the European population carries a genetic variant that leads to antibody resistance against anti-tumor necrosis factor (TNF) drugs, infliximab and adalimumab, and lose response.

Published in Gastroenterology, the Personalized anti-TNF therapy in Crohn disease study (PANTS), the largest cohort of its kind, looked at the clinical data and genetics of 1240 patients with Crohn disease starting anti-TNF treatment at 120 hospitals in the United Kingdom.

According to the press release, one of the major reasons that patients with Crohn and colitis lose response over time to anti-TNF treatment is the development of an immune response to the drug, or immunogenicity. Repeated administration of anti-TNF drugs causes the immune system to recognize the drug as a potential threat rather than a medicine, leading to the production of antibodies against the treatment.

In addition to reducing the efficacy 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% of the European population that increases risk of development of antibodies against infliximab and adalimumab 2-fold.

According to the Crohn’s and Colitis Foundation, Crohn disease is an inflammatory bowel disease that causes chronic inflammation of the gastrointestinal tract. The disease most commonly presents in young adults, adolescents, and children. Symptoms include urgent diarrhea, rectal bleeding, abdominal pain, profound fatigue, and weight loss.

The study researchers at the University of Exeter concluded 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.¹

Reference

• Crohn’s disease study identifies genetic variant with potential to personalise treatment [press release]. The University of Exeter website. Published October 7, 2019. http://www.exeter.ac.uk/news/featurednews/title_756823_en.html. Accessed October 9, 2019.
• Crohn’s & Colitis Foundation website. https://www.crohnscolitisfoundation.org/. Accessed October 9, 2019.