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

• 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-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/

Meaningful Response: The clinician’s perspective

This is not the only reason for a colonoscopy.