1. The only end-points of therapy that matter are mucosal healing, normal blood work, and negative radiologic studies.
Robert N. Baldassano, MD
Colman Family Chair in Pediatric IBD
Professor of Pediatrics
University of Pennsylvania School of Medicine Director, Center for Pediatric IBD
The Children's Hospital of Philadelphia

2. Are we changing the Natural History by using
clinical symptoms as our end-point??
Intestinal Resection
in Different Cohorts
Treat the patient
not the lab tests
No change in
operative rates 60
P = 0.81 40
% of Patients 20 12 24 36 48 60
Months After Diagnosis
6MP was standard
therapy at this time
Cosnes J, et al. Gut. 2005;54:237.

3. Crohn’s Disease Progression on “Conventional” Therapy in Children: 1988-2002
Inflammatory
34% at 5 yrs
Stricturing
Penetrating
Vernier-Massouille et al. Gastroenterology
2008;135:1106

4. Shifting CD Therapeutic Goals
ADDED GOALS
Heal the mucosa
Modify the natural history
of disease
Prevent complications!!
PREVIOUS GOALS
Induce & maintain clinical
remission
Improve quality of life
Minimize drug toxicity
Optimize surgical outcomes

5. Does good symptom control mean good disease control?

6. Cannabis induces a clinical response in patients with CD
21 patients randomized to placebo vs. cannabis with THC
Significant “response” in CDAI in THC group (90% vs. 40%) at 8 weeks
NO change in HCT or CRP
Conclusion: getting high lowers your CDAI.
Naftali, et al. CGH 2013

7. The CDAI- Subjective and Non-Specific
91 consecutive patients with CD or IBS
Higher CDAIs in IBS patients
Pain scores higher
(p=0.1)
183
Mean CDAI Score
157
Lahiff C. et al. Aliment Pharmacol Ther. 2013; 37(8):

8. Relationship Between Clinical Symptoms and Endoscopic Indices at Presentation of Acute CD
600
500
400
Crohn’s Disease Activity Index
( CDAI )
300
200
100
R=0.13; NS 5 10 15 20 25 30 35
Crohn’s Disease Endoscopic Index of Severity (CDEIS)
Modigliani R et al. Gastroenterology. 1990;98:811.

9. Lack of Correlation Between Endoscopy and Clinical Symptoms (Which One is Really Measuring the Disease?)
Endoscopy is not a biomarker, endoscopy is physical (visual) examination of the ileum and colon
Analogies
Psoriasis – physical (visual) examination showing presence and severity of typical skin lesions
Rheumatoid arthritis – physical examination showing swollen and tender joints + biomarkers
Clinical symptoms are a surrogate for endoscopy findings, not the other way around

10. MR Enterography 50 CD patients Ileocolonoscopy and MRE
Strong correlation between CDEIS and wall thickness, ulceration, enhancement, edema
R=0.82 for MRE score and CDEIS
MRE highly accurate for assessment of active disease
Rimola et al Gut 2009

11. This strategy requires a new treatment target.
Treat-to-Target IBD
This strategy requires a new treatment target.
Clinical remission
Control of inflammation (mucosal healing)
Deep Remission

12. Treat-to-Target
This approach is taken with other chronic, progressive diseases where there are clearly defined treatment targets
Hypertension, Diabetes and Rheumatoid Arthritis
No longer sufficient to aim to treat to symptom control

13. Deep Remission Goals Prevention of bowel damage
Reduction of long-term disability
Maintenance of good quality of life

14. Deep Remission after 1 year of treatment for UC is predictive of a decreased rate of colectomy
Froslie KF, et al. Gastro 2007

15. EXTEND Study
Time to Loss of Response at week 52 with and without Deep Remission (DR) at week 12
Colombel JF, et al. Clin Gastro Hep; 2014 (in press)

16. EXTEND Study
Quality of life and Productivity at week 52 with and without Deep Remission (DR) at week 12
Colombel JF, et al. Clin Gastro Hep ; 2014 (in press)

17. Meaningful Response: The clinician’s perspective
Spryliving.com March
This is not the only reason for a colonoscopy.