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 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). An 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). A new index (ADMIT-ASC) predicting steroid-responsiveness on the day of admission with acute severe colitis has been developed in Oxford and validated in Delhi and Brisbane.
• 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 being introduced into Phase 2 and 3 trials and clinical practice. This has reduced variance in endoscopic reporting from 73% to 14%, correlates closely with histology and  predicts outcomes. Currently working with a Canadian group (Satisfai) to develop AI reading of disease activity.
• Evaluation of novel therapies for inflammatory bowel disease (IBD): Global or National Chief Investigator of many clinical trials of therapy for IBD, some through to registration including budesonide MMX, a first in class small molecule for ulcerative colitis, stem cell transplantation for Crohn’s, post-operative prevention studies and devices. 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.
• Biology of IBD: Collaborating with scientists on multiomic and metabolomic evaluation of response to therapies for IBD, through A-TAP and others, to understand the drivers of inflammation, help select the most appropriate therapy for the individual patient and understand the molecular basis of symptoms in IBD. 
• 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 GI cohort for the Translational Gastroenterology Unit (Chief Investigator) in the clinical description/ research database and genetic characterisation of >3500 patients with IBD.   
• Outcomes and monitoring in IBD: Chair of a global group to develop patient outcome measures for IBD. Established real-time digital data collection for ulcerative colitis and Crohn’s disease using validated indices (TrueColours-IBD) in daily clinical practice, which monitors symptoms, quality of life (fortnightly) and outcomes (quarterly) in >2200 patients. The InSpectrum project in collaboration with the mathematical Institute involves multidimensional analysis of response to therapies and stochastical events  
• Gastrointestinal bleeding: The paradigm of liberal blood transfusion for acute gastrointestinal bleeding was challenged through the UK’s first cluster-randomised trial (Lancet 2015). On the steering group for the UK’s first national re-audit of GI bleeding, transfusion practice and outcomes (2021).

Simon Travis is the author of 7 books, 30 chapters and >300 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 24 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). Editorial Board of Gut (2015-20, IF 23.059) and Journal of Crohn’s & Colitis (IF 9.485), among other journals.