Transcript P - Advances in Inflammatory Bowel Diseases

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
Are we changing the Natural History by using
clinical symptoms as our end-point??
Treat the patient
not the lab tests
Intestinal Resection
in Different Cohorts
60
% of Patients
P = 0.81
No change in
operative rates
40
20
0
0
1978-82
1983-87
12
24
36
48
Months After Diagnosis
1988-92
60
1993-97
1998-2002
6MP was standard
therapy at this time
Cosnes J, et al. Gut. 2005;54:237.
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
3
Shifting CD Therapeutic Goals

PREVIOUS GOALS
Induce & maintain clinical
remission
 Improve quality of life
Minimize drug toxicity
 Optimize surgical outcomes

ADDED GOALS
Heal the mucosa
 Modify the natural history
of disease
Prevent complications!!
Does good symptom control mean
good disease control?
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
The CDAI- Subjective and Non-Specific
• Higher CDAIs in IBS
patients
• Pain scores higher
(p=0.1)
Mean CDAI Score
• 91 consecutive patients
with CD or IBS
183
157
Lahiff C. et al. Aliment Pharmacol Ther. 2013; 37(8):786- 94
Crohn’s Disease Activity Index
( CDAI )
Relationship Between Clinical Symptoms and
Endoscopic Indices at Presentation of Acute CD
600
500
400
300
200
100
R=0.13; NS
0
0
5
10
15
20
25
30
35
Crohn’s Disease Endoscopic Index of Severity (CDEIS)
Modigliani R et al. Gastroenterology. 1990;98:811.
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
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
Treat-to-Target
IBD
• This strategy requires a new treatment target.
– Clinical remission
– Control of inflammation (mucosal healing)
Deep Remission
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
Deep Remission
• Goals
– Prevention of bowel damage
– Reduction of long-term disability
– Maintenance of good quality of life
Deep Remission after 1 year of treatment for UC
is predictive of a decreased rate of colectomy
Froslie KF, et al. Gastro 2007
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)
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)
Meaningful Response: The clinician’s
perspective
This is not the only reason for a colonoscopy.
Spryliving.com March 2012 http://spryliving.com/articles/8-ways-to-a-hasslefree-colonoscopy/