Translational Gastroenterology Unit, John Radcliffe Hospital

Podcast: Translational Gastroenterology Unit, John Radcliffe Hospital

Podcast: Clinical Trials in Gastroenterology

Ulcerative colitis and Crohn’s disease (‘IBD’) are one of the central clinical and scientific
problems in Gastroenterology, affecting the lives of over 2 million people in Europe and their families, costing over €4bn/yr. The causes are unknown, but the rapid rise in cases in the Gulf, Indian subcontinent, East Asia and Latin America mirror changes that happened in Western Europe and North America fifty years ago. Predicting the prognosis, reliable metrics for clinical trials and novel therapy are pivotal to progress in a condition that predominantly affects young people, has a definable mortality and cure is still impossible. Our clinical research into IBD includes:

• Predictive indices for ulcerative colitis. After developing the Oxford predictive index for acute severe colitis in 1996, the index has been independently validated (2009), incorporated into practice (four UK National IBD Audits since 2008 and all international guidelines) and been the basis of the CONSTRUCT HTA-funded trial (2009-14). A new index for predicting the risk of acute severe colitis (2013) over the next 3 years from diagnosis, has now been independently replicated in Cambridge and Uppsala (2014)
• Endoscopic assessment of ulcerative colitis. An international programme of the world's leading IBD specialists created the first validated endoscopic index for ulcerative colitis (UC), now (2015) being introduced into Phase 2 and 3 trials and clinical practice. It is (2015) under consideration as the endoscopic index of choice for central reading in clinical trials. This has reduced variance in endoscopic reporting from 73% to 14%.
• Evaluation of novel therapies for inflammatory bowel disease (IBD): Global Chief Investigator of 8 clinical trials of therapy for IBD, some through to registration and UK CI or PI in 20 others, including a first in class small molecule for ulcerative colitis, stem cell transplantation for Crohn’s, anti-CD3 MAb for ulcerative colitis, post-operative prevention studies and devices (an adsorbent compound AST-120). As senior author on the first trial of an anti-IL17A MAb (secukinumab, Novartis), we were first to report that this exacerbated Crohn’s disease, in contrast to its therapeutic benefit in psoriasis and rheumatoid arthritis and that a SNP in the TLA1 gene might (in contrast) be associated with therapeutic benefit.
• Measurement of outcomes for clinical trials and practice: An explicit recommendation for defining robust criteria for entry into clinical trials of ulcerative colitis and endpoints helped reduce the placebo response from 20-30% in past trials of UC to <5% for budesonide MMX (Cosmo), leading to drug registration by the FDA and EMA (Global Chief Investigator). Development of the Oxford IBD cohort for the Translational Gastroenterology Unit (Co PI with Uhlig, Powrie, Keshav) in the clinical description/ research database and genetic characterisation of >2000 patients with IBD.   
• Gastrointestinal bleeding: The paradigm of liberal blood transfusion for acute gastrointestinal bleeding was challenged through the UK’s first cluster-randomised trial (Lancet 2015). Co-supervisor of the UK’s first prospective national audit of GI bleeding, transfusion practice and outcomes.
• Quality of life and burden of IBD: Chair of a global group to develop patient outcome measures for IBD through the Oxford Academic Health Sciences Network (2015-). Also developing real-time data collection in ulcerative colitis (TrueColours in IBD) to relate fluctuations in disease activity with the biology of the disease

Simon Travis is the author of 6 books, 29 chapters and over 230 papers. He was President of the European Crohn’s and Colitis Organisation (ECCO), an elected Member of the International Organisation of Inflammatory Bowel Disease and author of 22 peer-reviewed international guidelines. Member of Council of the British Society of Gastroenterology (2004-2007) and Chair of the scientific committee of ECCO (2007-2010). He is on the Editorial Board of Gut (IF 14.8) and Journal of Crohn’s & Colitis (IF 6.2), among other journals.