Transcript IBDWG Audio Presentation

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 CHARM
by 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 patients
with 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 progression
to 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 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?)