1. Therapeutic algorithms for Crohn’s disease: Where are we in 2012?

2. Classic management of CD is sequential

3. A competing treatment concept!

4. Most Crohn’s disease patients will require surgery

5. Mortality in Crohn’s disease

6. Case presentation: Active CD

7. Endoscopy shows both TI and cecal involvement

8. Endoscopic image showing deep ulcerations

9. National Cooperative Crohn's Disease Study (NCCDS): Induction of remission in Crohn's disease

10. Mesalamine (5-ASA): Induction of remission in Crohn's disease

11. 5-ASA for induction of remission in Crohn's disease: A meta-analysis

12. Corticosteroids in IBD

13. Budesonide absorption and metabolism

14. Budesonide vs mesalamine: Induction of remission

15. Azathioprine (AZA) maintenance therapy after corticosteroid-induction in Crohn's disease

16. Combination induction therapy 6-mercaptopurine (6-MP) + prednisone

17. Rates of surgery for CD and the use of immunosuppressives over 3 decades

18. Methotrexate: Widely used to treat severe arthritis in the past

19. Methotrexate results: Remission

20. Results: Time to relapse

21. Anti-TNFα-inhibitors

22. Maintenance of remission in Crohn's disease

23. Adalimumab + methotrexate in early rheumatoid arthritis: PREMIER study

24. Remission rate at Week 52 in CHARM by immunosuppressive use

25. Azathioprine monotherapy vs infliximab + azathioprine in steroid-dependent CD

26. Early combination therapy vs conventional management of Crohn’s disease

27. Use of drug with conventional or early aggressive therapy

28. Early aggressive therapy vs conventional management of Crohn’s disease

29. Early combination therapy vs conventional management of Crohn’s disease: Complete disappearance of ulceration

30. SONIC: Clinical remission without corticosteroids at Week 26

31. Optimum efficacy by treatment of patients with objective measures of inflammation

32. Schematic overview of COMMITT trial design

33. COMMITT: Proportion of patients with treatment success

34. OK, so we just treat everyone with combination therapy forever!!??

35. Predictors of rapid progression to surgery

36. Prognosis of CD patients with severe colonic ulceration

37. Positive serology and risk of progression

38. High risk patients should be considered for early treatment with combined therapy

39. Back to our CD case

40. Kaplan-Meier CD-related hospitalization: CHARM

41. Safety data from the TREAT registry

42. Lymphoma risk and IBD  Lymphoma risk is well established  Special case of HTCL  Non-melanoma skin cancer similarly elevated  Highly concerning to patients

43. Methotrexate and lymphoma risk “The hypothesis that disease-modifying drugs, and in particular methotrexate, would increase the lymphoma risk receives little support.” Baecklund et al, Current Opinion Rheumatology 2004; 16(3): 254–61 “Insufficient data are available to fully assess the risk of lymphoma and malignancies, although there is no strong evidence of increased risk.” Salliot & van der Heijde, Ann Rheum Dis 2009; 68: 1100–4 “Recent work suggests that it is the disease itself, not its treatment, that is associated with increased risk of lymphoma in patients with rheumatoid arthritis.” Kaiser, Clinical Lymphoma Myeloma 2008; 8(2): 87–93

45. Four emerging concepts in CD  Objective evidence of the presence of inflammation should drive clinical decision making, not the presence of symptoms in isolation  The pharmacokinetics of TNFα-inhibitors are complex and therapy should be optimized for individual patients  Combining antimetabolite therapy and a TNFα-inhibitor results in optimal efficacy and protects the latter against sensitization  Step-care is obsolete (CD vs UC?)