Reducing risk, improving outcomes: development of personalised strategies to reduce the impact of immunogenicity to biologic therapies

Summary

Lay summary  

Infliximab and adalimumab are anti-TNF medicines used to treat ulcerative colitis and Crohn’s disease. These medicines work by blocking a protein in the body call tumour necrosis factor (TNF). TNF plays an important part in the immune system, but in some people the body produces too much, which causes inflammation and damage to the gut.  These medicines work well for most people, but unfortunately over time, often stop working. One of the reasons why these drugs stop working is because the body recognises infliximab and adalimumab as a possible threat, rather than a medicine, leading to the production of antibodies. Antibodies are important proteins that usually protect us from infection. However, when antibodies target infliximab and adalimumab they stop the medicines working properly and can also cause skin rash, difficulty breathing and low blood pressure. Our previous research has found that some people have changes in their DNA (body building blocks) that promote these antibodies against anti-TNF drugs, whilst other people can successfully continue on treatment without forming antibodies.

Using clinical, laboratory and genetic data held by the Gut Reaction - NIHR IBD Bioresource we aim to further investigate genetic causes for why people develop antibodies to anti-TNF medicines. We will also identify if these DNA changes are associated with loss of response and side effects with infliximab, adalimumab and other medicines used to treat people with ulcerative colitis and Crohn’s disease. 

Patient Benefit 

We hope this research will lead to the development of a genetic test which will identify which patients are more likely to form antibodies to infliximab and adalimumab. This test will be carried out at the time of diagnosis and help doctors and nurses choose the safest and most effective medicines for patients with ulcerative colitis and Crohn’s disease.