![Page 1: Therapeutic algorithms for Crohn’s disease: Where are we in 2012?](https://reader036.vdocuments.net/reader036/viewer/2022062516/56649dd35503460f94aca32b/html5/thumbnails/1.jpg)
Therapeutic algorithms for Crohn’s disease:
Where are we in 2012?
![Page 2: Therapeutic algorithms for Crohn’s disease: Where are we in 2012?](https://reader036.vdocuments.net/reader036/viewer/2022062516/56649dd35503460f94aca32b/html5/thumbnails/2.jpg)
Classic management of CD is sequential
![Page 3: Therapeutic algorithms for Crohn’s disease: Where are we in 2012?](https://reader036.vdocuments.net/reader036/viewer/2022062516/56649dd35503460f94aca32b/html5/thumbnails/3.jpg)
A competing treatment concept!
![Page 4: Therapeutic algorithms for Crohn’s disease: Where are we in 2012?](https://reader036.vdocuments.net/reader036/viewer/2022062516/56649dd35503460f94aca32b/html5/thumbnails/4.jpg)
Most Crohn’s disease patients will require surgery
![Page 5: Therapeutic algorithms for Crohn’s disease: Where are we in 2012?](https://reader036.vdocuments.net/reader036/viewer/2022062516/56649dd35503460f94aca32b/html5/thumbnails/5.jpg)
Mortality in Crohn’s disease
![Page 6: Therapeutic algorithms for Crohn’s disease: Where are we in 2012?](https://reader036.vdocuments.net/reader036/viewer/2022062516/56649dd35503460f94aca32b/html5/thumbnails/6.jpg)
Case presentation: Active CD
![Page 7: Therapeutic algorithms for Crohn’s disease: Where are we in 2012?](https://reader036.vdocuments.net/reader036/viewer/2022062516/56649dd35503460f94aca32b/html5/thumbnails/7.jpg)
Endoscopy shows both TI and cecal involvement
![Page 8: Therapeutic algorithms for Crohn’s disease: Where are we in 2012?](https://reader036.vdocuments.net/reader036/viewer/2022062516/56649dd35503460f94aca32b/html5/thumbnails/8.jpg)
Endoscopic image showing deep ulcerations
![Page 9: Therapeutic algorithms for Crohn’s disease: Where are we in 2012?](https://reader036.vdocuments.net/reader036/viewer/2022062516/56649dd35503460f94aca32b/html5/thumbnails/9.jpg)
National Cooperative Crohn's Disease Study (NCCDS): Induction of remission in Crohn's disease
![Page 10: Therapeutic algorithms for Crohn’s disease: Where are we in 2012?](https://reader036.vdocuments.net/reader036/viewer/2022062516/56649dd35503460f94aca32b/html5/thumbnails/10.jpg)
Mesalamine (5-ASA): Induction of remission in Crohn's disease
![Page 11: Therapeutic algorithms for Crohn’s disease: Where are we in 2012?](https://reader036.vdocuments.net/reader036/viewer/2022062516/56649dd35503460f94aca32b/html5/thumbnails/11.jpg)
5-ASA for induction of remission in Crohn's disease: A meta-analysis
![Page 12: Therapeutic algorithms for Crohn’s disease: Where are we in 2012?](https://reader036.vdocuments.net/reader036/viewer/2022062516/56649dd35503460f94aca32b/html5/thumbnails/12.jpg)
Corticosteroids in IBD
![Page 13: Therapeutic algorithms for Crohn’s disease: Where are we in 2012?](https://reader036.vdocuments.net/reader036/viewer/2022062516/56649dd35503460f94aca32b/html5/thumbnails/13.jpg)
Budesonide absorption and metabolism
![Page 14: Therapeutic algorithms for Crohn’s disease: Where are we in 2012?](https://reader036.vdocuments.net/reader036/viewer/2022062516/56649dd35503460f94aca32b/html5/thumbnails/14.jpg)
Budesonide vs mesalamine: Induction of remission
![Page 15: Therapeutic algorithms for Crohn’s disease: Where are we in 2012?](https://reader036.vdocuments.net/reader036/viewer/2022062516/56649dd35503460f94aca32b/html5/thumbnails/15.jpg)
Azathioprine (AZA) maintenance therapy after corticosteroid-induction in Crohn's disease
![Page 16: Therapeutic algorithms for Crohn’s disease: Where are we in 2012?](https://reader036.vdocuments.net/reader036/viewer/2022062516/56649dd35503460f94aca32b/html5/thumbnails/16.jpg)
Combination induction therapy 6-mercaptopurine (6-MP) + prednisone
![Page 17: Therapeutic algorithms for Crohn’s disease: Where are we in 2012?](https://reader036.vdocuments.net/reader036/viewer/2022062516/56649dd35503460f94aca32b/html5/thumbnails/17.jpg)
Rates of surgery for CD and the use of immunosuppressives over 3 decades
![Page 18: Therapeutic algorithms for Crohn’s disease: Where are we in 2012?](https://reader036.vdocuments.net/reader036/viewer/2022062516/56649dd35503460f94aca32b/html5/thumbnails/18.jpg)
Methotrexate: Widely used to treat severe arthritis in the past
![Page 19: Therapeutic algorithms for Crohn’s disease: Where are we in 2012?](https://reader036.vdocuments.net/reader036/viewer/2022062516/56649dd35503460f94aca32b/html5/thumbnails/19.jpg)
Methotrexate results: Remission
![Page 20: Therapeutic algorithms for Crohn’s disease: Where are we in 2012?](https://reader036.vdocuments.net/reader036/viewer/2022062516/56649dd35503460f94aca32b/html5/thumbnails/20.jpg)
Results: Time to relapse
![Page 21: Therapeutic algorithms for Crohn’s disease: Where are we in 2012?](https://reader036.vdocuments.net/reader036/viewer/2022062516/56649dd35503460f94aca32b/html5/thumbnails/21.jpg)
Anti-TNFα-inhibitors
![Page 22: Therapeutic algorithms for Crohn’s disease: Where are we in 2012?](https://reader036.vdocuments.net/reader036/viewer/2022062516/56649dd35503460f94aca32b/html5/thumbnails/22.jpg)
Maintenance of remission in Crohn's disease
![Page 23: Therapeutic algorithms for Crohn’s disease: Where are we in 2012?](https://reader036.vdocuments.net/reader036/viewer/2022062516/56649dd35503460f94aca32b/html5/thumbnails/23.jpg)
Adalimumab + methotrexate in early rheumatoid arthritis: PREMIER study
![Page 24: Therapeutic algorithms for Crohn’s disease: Where are we in 2012?](https://reader036.vdocuments.net/reader036/viewer/2022062516/56649dd35503460f94aca32b/html5/thumbnails/24.jpg)
Remission rate at Week 52 in CHARMby immunosuppressive use
![Page 25: Therapeutic algorithms for Crohn’s disease: Where are we in 2012?](https://reader036.vdocuments.net/reader036/viewer/2022062516/56649dd35503460f94aca32b/html5/thumbnails/25.jpg)
Azathioprine monotherapy vs infliximab + azathioprine in steroid-dependent CD
![Page 26: Therapeutic algorithms for Crohn’s disease: Where are we in 2012?](https://reader036.vdocuments.net/reader036/viewer/2022062516/56649dd35503460f94aca32b/html5/thumbnails/26.jpg)
Early combination therapy vs conventional management of Crohn’s disease
![Page 27: Therapeutic algorithms for Crohn’s disease: Where are we in 2012?](https://reader036.vdocuments.net/reader036/viewer/2022062516/56649dd35503460f94aca32b/html5/thumbnails/27.jpg)
Use of drug with conventional or early aggressive therapy
![Page 28: Therapeutic algorithms for Crohn’s disease: Where are we in 2012?](https://reader036.vdocuments.net/reader036/viewer/2022062516/56649dd35503460f94aca32b/html5/thumbnails/28.jpg)
Early aggressive therapy vs conventional management of Crohn’s disease
![Page 29: Therapeutic algorithms for Crohn’s disease: Where are we in 2012?](https://reader036.vdocuments.net/reader036/viewer/2022062516/56649dd35503460f94aca32b/html5/thumbnails/29.jpg)
Early combination therapy vs conventional management of Crohn’s disease:
Complete disappearance of ulceration
![Page 30: Therapeutic algorithms for Crohn’s disease: Where are we in 2012?](https://reader036.vdocuments.net/reader036/viewer/2022062516/56649dd35503460f94aca32b/html5/thumbnails/30.jpg)
SONIC: Clinical remission without corticosteroids at Week 26
![Page 31: Therapeutic algorithms for Crohn’s disease: Where are we in 2012?](https://reader036.vdocuments.net/reader036/viewer/2022062516/56649dd35503460f94aca32b/html5/thumbnails/31.jpg)
Optimum efficacy by treatment of patientswith objective measures of inflammation
![Page 32: Therapeutic algorithms for Crohn’s disease: Where are we in 2012?](https://reader036.vdocuments.net/reader036/viewer/2022062516/56649dd35503460f94aca32b/html5/thumbnails/32.jpg)
Schematic overview of COMMITT trial design
![Page 33: Therapeutic algorithms for Crohn’s disease: Where are we in 2012?](https://reader036.vdocuments.net/reader036/viewer/2022062516/56649dd35503460f94aca32b/html5/thumbnails/33.jpg)
COMMITT: Proportion of patients with treatment success
![Page 34: Therapeutic algorithms for Crohn’s disease: Where are we in 2012?](https://reader036.vdocuments.net/reader036/viewer/2022062516/56649dd35503460f94aca32b/html5/thumbnails/34.jpg)
OK, so we just treat everyone with combination therapy forever!!??
![Page 35: Therapeutic algorithms for Crohn’s disease: Where are we in 2012?](https://reader036.vdocuments.net/reader036/viewer/2022062516/56649dd35503460f94aca32b/html5/thumbnails/35.jpg)
Predictors of rapid progressionto surgery
![Page 36: Therapeutic algorithms for Crohn’s disease: Where are we in 2012?](https://reader036.vdocuments.net/reader036/viewer/2022062516/56649dd35503460f94aca32b/html5/thumbnails/36.jpg)
Prognosis of CD patients with severe colonic ulceration
![Page 37: Therapeutic algorithms for Crohn’s disease: Where are we in 2012?](https://reader036.vdocuments.net/reader036/viewer/2022062516/56649dd35503460f94aca32b/html5/thumbnails/37.jpg)
Positive serology and risk of progression
![Page 38: Therapeutic algorithms for Crohn’s disease: Where are we in 2012?](https://reader036.vdocuments.net/reader036/viewer/2022062516/56649dd35503460f94aca32b/html5/thumbnails/38.jpg)
High risk patients should be considered for early treatment with combined therapy
![Page 39: Therapeutic algorithms for Crohn’s disease: Where are we in 2012?](https://reader036.vdocuments.net/reader036/viewer/2022062516/56649dd35503460f94aca32b/html5/thumbnails/39.jpg)
Back to our CD case
![Page 40: Therapeutic algorithms for Crohn’s disease: Where are we in 2012?](https://reader036.vdocuments.net/reader036/viewer/2022062516/56649dd35503460f94aca32b/html5/thumbnails/40.jpg)
Kaplan-Meier CD-related hospitalization: CHARM
![Page 41: Therapeutic algorithms for Crohn’s disease: Where are we in 2012?](https://reader036.vdocuments.net/reader036/viewer/2022062516/56649dd35503460f94aca32b/html5/thumbnails/41.jpg)
Safety data from the TREAT registry
![Page 42: Therapeutic algorithms for Crohn’s disease: Where are we in 2012?](https://reader036.vdocuments.net/reader036/viewer/2022062516/56649dd35503460f94aca32b/html5/thumbnails/42.jpg)
Lymphoma risk and IBD
Lymphoma risk is well established
Special case of HTCL
Non-melanoma skin cancer similarly elevated
Highly concerning to patients
![Page 43: Therapeutic algorithms for Crohn’s disease: Where are we in 2012?](https://reader036.vdocuments.net/reader036/viewer/2022062516/56649dd35503460f94aca32b/html5/thumbnails/43.jpg)
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
![Page 44: Therapeutic algorithms for Crohn’s disease: Where are we in 2012?](https://reader036.vdocuments.net/reader036/viewer/2022062516/56649dd35503460f94aca32b/html5/thumbnails/44.jpg)
![Page 45: Therapeutic algorithms for Crohn’s disease: Where are we in 2012?](https://reader036.vdocuments.net/reader036/viewer/2022062516/56649dd35503460f94aca32b/html5/thumbnails/45.jpg)
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?)