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
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The only end-points of therapy that matter are mucosal healing, normal blood work, and negative radiologic studies. Robert N. Baldassano, MD Colman Family.
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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 IBDProfessor 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 usingclinical symptoms as our end-point??
Cosnes J, et al. Gut. 2005;54:237.
1978-82 1983-87 1988-92 1993-97 1998-2002
120 24 36 48 60
20
40
60
Months After Diagnosis
% o
f P
atie
nts
Intestinal Resectionin Different Cohorts
P = 0.81
0
No change inoperative rates
6MP was standard therapy at this time
Treat the patientnot the lab tests
Crohn’s Disease Progression on “Conventional” Therapy in Children: 1988-2002
Vernier-Massouille et al. Gastroenterology 2008;135:1106
Inflammatory
Stricturing
Penetrating
34% at 5 yrs
3
Shifting CD Therapeutic Goals
PREVIOUS GOALSInduce & maintain clinical remission Improve quality of lifeMinimize drug toxicity Optimize surgical outcomes
ADDED GOALSHeal the mucosa Modify the natural history of diseasePrevent 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
• 91 consecutive patients with CD or IBS• Higher CDAIs in IBS
patients • Pain scores higher
The CDAI- Subjective and Non-Specific
Lahiff C. et al. Aliment Pharmacol Ther. 2013; 37(8):786- 94
Mea
n C
DA
I S
core
183
157
(p=0.1)
Relationship Between Clinical Symptoms and Endoscopic Indices at Presentation of Acute CD
R=0.13; NS
Croh
n’s
Dis
ease
Acti
vity
Inde
x( C
DAI
)Cr
ohn’
s D
isea
se A
ctivi
ty In
dex
( CD
AI )
Crohn’s Disease Endoscopic Index of Severity (CDEIS)
00
100
200
300
400
500
600
5 10 15 20 25 30 35
Modigliani R et al. Gastroenterology. 1990;98:811.
Lack of Correlation Between Endoscopyand 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
• 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-TargetIBD
• 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
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
EXTEND Study
Colombel JF, et al. Clin Gastro Hep ; 2014 (in press)
Spryliving.com March 2012 http://spryliving.com/articles/8-ways-to-a-hassle-free-colonoscopy/