Therapeutic algorithms for Crohn’s disease:

Where are we in 2012?

Classic management of CD is sequential

A competing treatment concept!

Most Crohn’s disease patients will require surgery

Mortality in Crohn’s disease

Case presentation: Active CD

Endoscopy shows both TI and cecal involvement

Endoscopic image showing deep ulcerations

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

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

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

Corticosteroids in IBD

Budesonide absorption and metabolism

Budesonide vs mesalamine: Induction of remission

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

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

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

Methotrexate: Widely used to treat severe arthritis in the past

Methotrexate results: Remission

Results: Time to relapse

Anti-TNFα-inhibitors

Maintenance of remission in Crohn's disease

Adalimumab + methotrexate in early rheumatoid arthritis: PREMIER study

Remission rate at Week 52 in CHARMby immunosuppressive use

Azathioprine monotherapy vs infliximab + azathioprine in steroid-dependent CD

Early combination therapy vs conventional management of Crohn’s disease

Use of drug with conventional or early aggressive therapy

Early aggressive therapy vs conventional management of Crohn’s disease

Early combination therapy vs conventional management of Crohn’s disease:

Complete disappearance of ulceration

SONIC: Clinical remission without corticosteroids at Week 26

Optimum efficacy by treatment of patientswith objective measures of inflammation

Schematic overview of COMMITT trial design

COMMITT: Proportion of patients with treatment success

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

Predictors of rapid progressionto surgery

Prognosis of CD patients with severe colonic ulceration

Positive serology and risk of progression

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

Back to our CD case

Kaplan-Meier CD-related hospitalization: CHARM

Safety data from the TREAT registry

Lymphoma risk and IBD

Lymphoma risk is well established

Special case of HTCL

Non-melanoma skin cancer similarly elevated

Highly concerning to patients

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

Four emerging concepts in CD

Objective evidence of the presence of inflammation should drive clinical decision making, not the presenceof 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?)