William J. Sandborn, MD Professor & Chief, Division of Gastroenterology

1. Asymptomatic UC patients on an immunomodulator with persistent moderate mucosal inflammation should either add a biologic or switch to a biologic William J. Sandborn, MD Professor & Chief, Division of Gastroenterology Director, UCSD IBD Center

2. Arguments for treating to target in ulcerative colitis • It is feasible • It is associated with a reduced rate of colectomy and an increased rate of steroid-free remission • It is associated with a reduced rate of colorectal dysplasia and cancer • It is logical and obviously the right thing to do

3. It is feasible:Treating to target in ulcerative colitis

4. Bouguen G, Levesque BG, Sandborn WJ. Clin Gastroenterol Hepatol. 2014 (In Press) Treat-to-Target Algorithm ) CRP, C-reactive protein.

5. Study population 144 patients 31 patients Bougen G, Levesque B, Sandborn W. Inflam Bowel Dis 2014 (In Press) 53 patients 60 patients STUDY POPULATION 45 patients 15 patients

6. Endoscopicprocedures 159 endoscopic procedures 92 colonoscopy 67 flexible sigmoidoscopy 60 patients had at least 2 consecutive endoscopic procedures 26 patients (43%): 3 consecutive procedures 8 patients (13%): 4 consecutive procedures 2 patients (3%): 5 consecutive procedures median follow-up of 76 weeks (IQR75 54-92) Endoscopy 1 Median time 19 weeks Endoscopy 2 Median time 17 weeks Endoscopy 3 Median time 20 weeks Endoscopy 4 Bougen G, Levesque B, Sandborn W. Inflam Bowel Dis 2014 (In Press)

7. Adjustment in medicaltherapy and surgery Overall cohort : 5-ASA introduction: 2 events 5-ASA increase dose: 6 events Oral steroids introduction: 11 events Anti-TNF Introduction: 20 events Anti-TNF Optimization/switch: 11 events Immunosuppression introduction: 18 patients Surgery: 7 patients MEDIAN FOLLOW-UP = 76 weeks (IQR75 44-79) MEDIAN TIME BETWEEN PROCEDURE = 25 weeks (16-42) Bougen G, Levesque B, Sandborn W. Inflam Bowel Dis 2014 (In Press)

8. Cumulative probability of reaching mucosal healing and histologic healing Bougen G, Levesque B, Sandborn W. Inflam Bowel Dis 2014 (In Press)

9. Reaching mucosal healing according to medical management during follow up multivariate analysis: adjustments in medical therapy Bougen G, Levesque B, Sandborn W. Inflam Bowel Dis 2014 (In Press)

10. It is associated with a reduced rate of colectomy and an increased rate of steroid-free remission

11. Pts with MH at 1 year p=0.02 Pts without MH at 1 year Mucosal Healing after treatment as predictor of subsequent disease course in ulcerative colitis Frøslie KF, et al. Gastroenterology. 2007;133:412-422.

12. Mucosal Healing and Time to Colectomy in Infliximab-treated Patients: Endoscopy Subscore 0 = NORMAL 1 = MILD 2 = MODERATE 3 = SEVERE Colombel JF, Sandborn WJ, et al. Gastroenterology 2011;141:1194-1201.

13. Association Between Week 8 Mayo Endoscopy Sub-score and and Corticosteroid-Free Symptomatic Remission at Week 30 During Anti-TNF Antibody Therapy Colombel JF, Sandborn WJ. Gastroenterology 2011

14. It is associated with a reduced rate of colorectal dysplasia and cancer

15. Predicting cancer risk in UC 12 P<0.001 Odds ratio for colorectal cancer (95% CI) 10 Disease extent PSC Disease duration Family history of CRC 8 6 P=0.001 OR=5.13 4 OR=2.54 2 0 Histological inflammation score Colonoscopy inflammation score OR for each 1 point increase in inflammatory score Rutter et al Gastroenterology 2004;126:451

16. It is logical and obviously the right thing to do

17. Parachute use to prevent death and major trauma related to gravitational challenge: a systematic review of randomized controlled trials • Objectives: To determine whether parachutes are effective in preventing major trauma related to gravitational challenge • Design: Systematic review of randomized controlled trials • Data sources: Medline, Web of Science, Embase, and the Cochrane Library databases; appropriate internet sites and citation lists • Study selection: Studies showing the effects of using a parachute during free fall • Main outcome measure: Death or major trauma, defined as an injury severity score > 15 Gordon CS. BMJ 2003

18. Parachute use to prevent death and major trauma related to gravitational challenge: a systematic review of randomized controlled trials • Results: We were unable to identify any randomized controlled trials of parachute intervention • Conclusions: As with many interventions intended to prevent ill health, the effectiveness of parachutes has not been subjected to rigorous evaluation by using randomized controlled trials. Advocates of evidence based medicine have criticized the adoption of interventions evaluated by using only observational data. We think that everyone might benefit if the most radical protagonists of evidence based medicine organized and participated in a double blind, randomized, placebo controlled, crossover trial of the parachute Gordon CS. BMJ 2003

19. It is logical and obviously the right thing to do • You don’t need a randomized controlled trial to determine that using a parachute is the right thing to do • Do you need a randomized controlled trial to determine that healing the colon is the right thing to do?

20. Treating to Mucosal Healing in Ulcerative Colitis • It is feasible • It is associated with a reduced rate of colectomy and an increased rate of steroid-free remission • It is associated with a reduced rate of colorectal dysplasia and cancer • It is logical and obviously the right thing to do