Dr Tariq Ahmad

2011 - Guts UK Development Grant

Title: UK IBD Genetics Consortium Study of anti-TNF pharmacogenomics – predicting response and toxicity to anti-TNF drugs

Project Start Date: 7 November 2011

Completion Date: March 2016

The introduction of drugs directed against tumour necrosis factor alpha (anti-TNF) has greatly advanced the treatment of Crohn’s disease. Infliximab and Adalimumab are effective in severe Crohn’s disease, lead to healing of the inflamed bowel, reducing hospital admissions and surgery, and improving quality of life for patients. However anti-TNF drugs are expensive (~£15,000 per patient per year), 10-30% of patients fail to respond, and a further 20-50% lose response after 12 months of treatment. Other patients experience unpredictable serious side effects such as infections, cancers and disorders of the nervous system. An ability to predict which patients are likely to benefit, and least likely to suffer side effects will allow these drugs to be used in a safer, more cost-effective manner, tailored to the individual patient.

Recent advances in genetic technology have been successfully employed to unravel the genes that cause Crohn’s disease. We will utilise the same genetic technology to investigate the causes for anti-TNF non-response, loss of response and serious drug side effects. We hope that the data generated will permit the development of predictive tests that can be used in the clinic to personalise care for patients with Crohn’s disease.

The UKIBD Genetic Consortium will conduct 2 parallel UK wide pharmacogenetic projects supported by Guts UK, the International Serious Adverse Events Consortium and the NIHR. Response to anti-TNF drugs will be investigated in a prospective study using strict definitions of response assessed at week 14 and 54. The collection of clinical data will be aligned and supported by the Royal College of Physicians IBD Biologics Database and research visits will be scheduled to coincide with clinic or infusion appointments. Serious side effects to anti-TNF drugs will be studied in a case control study and patients will be asked to attend a single research visit.