Investigation of the Clinical,Serological and Genetic Factors That Determine Primary Non-response, Loss of Response and Adverse Drug Reactions to Anti-TNF Drugs in Patients With Active Luminal Crohn's Disease

This is a prospective uncontrolled cohort study investigating primary non-response (PNR), loss of response (LOR) and adverse drug reactions (ADR) to IFX and ADA in patients with severe active luminal Crohn's disease. The primary objective of this study is to investigate the mechanisms that underlie PNR, LOR, ADRs and remission after anti-TNF withdrawal. The secondary aims are to develop personalised anti-TNF treatment strategies, through the identification of clinically meaningful serological and genetic predictive markers.

This study builds on the achievements of the UK and international IBDGC in identifying IBD susceptibility genes. These discoveries have provided important insights into disease pathogenesis but are not expected to have an impact in the clinic for a number of years. This study aims to take genetics and biomarker discovery into the IBD clinic to address questions of immediate clinical importance.

The study will commence in February 2013 utilising the network of 120 UK hospitals currently participating in the UK IBDGC pharmacogenetic programme (www.ibdresearch.co.uk). The collection of clinical data is aligned with the data being collected by the Royal College of Physicians UK IBD Biologics Audit. The clinical data for PANTS will be collected separately using a dedicated application held within the N3 network (www.pantsdb.co.uk). In order to avoid duplicate data entry we will share relevant anonymised data with the UK IBD Biologics Audit (and in due course with the UK IBD registry). The PANTS study aims to build a bio-resource for use by the UK IBD scientific community. Anonymised data will be made available to interested parties following appropriate ethical approval and consideration by the scientific management committee.

Patients will not be randomly allocated to one therapy or another and no attempt will be made to match populations including control for disease activity. Therefore the study has not been designed to directly compare PNR or LOR rates between IFX and ADA.

This observational study is funded by CORE, the British Society of Gastroenterology research charity and by unrestricted educational grants from Merck Sharp & Dohme (MSD) and AbbVie. The sponsor of the study is the Royal Devon and Exeter NHS Foundation Trust.