Crohn’s Disease: Managing and Monitoring
Mucosal Healing in the Small Bowel
5-000-482
Mucosal Healing
• Mucosal healing after one year of treatment is
predictive of reduced subsequent disease activity and
decreased need for active treatment1
• These results strengthen the use of mucosal healing as a
clinical indicator and treatment goal in inflammatory
bowel disease (IBD)1
• Results from an endoscopic substudy of ACCENT 1 (A
Crohn’s disease Clinical trial Evaluating infliximab in a
New long term Treatment regimen) suggest that
objective endpoints such as mucosal healing may end up
being clinically meaningful, and that treatment directed
toward such endpoints may result in improved long-term
outcomes in Crohn’s disease (CD)2
1. Froslie KF et al. Gastroenterology. 2007;133(2):412-422.
2. Loftus EV. Rev Gastroenterol Disord. 2007;7(suppl 2):S8-S16.
Mucosal Healing: Long-term Outcomes
in Crohn’s Disease
• Mucosal healing by long-term maintenance
infliximab treatment was associated with an
improved long-term outcome of disease, especially
with a lower need for hospitalization and major
abdominal surgeries
Schnitzler R et al. Inflamm Bowel Dis. 2009;15(9):1295-301.
Does Mucosal Healing Matter?
• In most recent pharmaceutical trials, the
documentation of endoscopic healing has become a
critical component of outcome measurement
• Additionally, studies are needed to demonstrate
that mucosal healing, in addition to symptom
control, should be a primary goal of therapy for CD
• Capsule endoscopy (CE) may play a role in
demonstrating/monitoring mucosal healing
Shergill AK et al. World J Gastroenterol. 2008;14(17):2670-2677.
Capsule Endoscopy Images of Mucosal Healing
Before and After Therapy
• The aim of this study was to evaluate the efficacy of infliximab as a
treatment of chronic refractory pouchitis complicated by ileitis as
diagnosed by CE
• Short-term treatment with infliximab determined clinical remission in 90% of
patients with chronic refractory pouchitis and/or ileitis
• Endoscopic/histologic healing of lesions in 80% of patients with refractory
pouchitis and/or ileitis
• Only one patient’s disease was unresponsive to therapy
Capsule Endoscopy Images:
Before Therapy
After Therapy
Calabrese et al. Aliment Pharmacol Ther. 2008;27(9):759-764.
Mucosal Healing Measured by Capsule Endoscopy:
Published Trial
• Efthymiou et al assessed correlation between
clinical response and mucosal healing of the small
bowel using CE
• In this small study (n=40), the number of large
ulcers showed statistically significant improvement
after treatment (p=.01)
• In this study, the endoscopic lesions of 42.5% of
patients would not have been able to be assessed
by ileocolonoscopy alone (the lesions were more
proximal SB)
• CE was able to detect more small bowel lesions and
monitor their healing more than would have been
possible with ileocolonoscopy alone
Efthymiou A et al. Inflamm Bowel Dis. 2008;14(11):1542-1547.
Endoscopic Parameters
Before and After Treatment
Before
Treatment
After Treatment
p
Number of large
ulcersa
8.3 ± 1.4
5.0 ± 0.8
.01
Number of
aphthous ulcersa
26.5 ± 7.5
12.7 ± 2.3
.07
Time percentage
of lesions visiblea
22.0 ± 3.1
17.8 ± 2.5
.08
Efthymiou A et al. Inflamm Bowel Dis. 2008;14(11):1542-1547.
a Mean
± SEM.
Mucosal Healing Measured by Capsule
Endoscopy: Case Study
• Female patient diagnosed with CD using CE after
other modalities failed to identify moderate to
severe disease limited to the small bowel
• Only reported symptoms of obscure GI bleeding and
occasional loose stools
• Complete mucosal healing observed by CE after 7
months of treatment with 6-mercaptopurine and
mesalamine
• Monitoring response to therapy necessitated serial
CE to demonstrate mucosal healing over time
Akhtar RY et al. Am J Gastroenterol. 2009;104(4):1065-1067.
Clinical Impact of Capsule Endoscopy Findings of
Mucosal Healing in the Management of Crohn’s Disease
• Multiple studies determined that CE can detect subtle
mucosal abnormalities of the small bowel (fissures,
aphthous ulcers) that may be missed by other
modalities1
• CE is a valuable tool not only in the evaluation of CD, but also
in the evaluation of its endoscopic severity1
• High diagnostic yield of CE influences disease
management and clinical outcomes2,3
• As a result of CE findings, CD therapy was changed in 64% of
cases3
1. Efthymiou et al. Inflamm Bowel Disease 2008;14(11):1542-1547.
2. Toy E et al. Am J Gastroenterol. 2008;103(12):3022-3028.
3. Lorenzo-Zúñiga V et al. Dig Dis Sci. 2010;55(2):411-4.
Need for a Capsule Endoscopy Scoring Index
• Lack of unified method of categorizing findings of
CE considered a limitation of early adoption
• No standard when describing small bowel inflammatory
lesions in terms of their extent and severity
• No one language for findings, no severity scale of mucosal
disease activity or threshold for disease diagnosis
• Capsule Endoscopy Scoring Indices
• Capsule Endoscopy Crohn's Disease Activity Index (CECDAI)
• Lewis Score
Lewis B. World J Gastroenterol. 2008;14(26):4137-4141.
Capsule Endoscopy Crohn's Disease Activity
Index (CECDAI)
• Scoring system for CECDAI
• Endoscopic score based on:
•
•
•
•
Inflammation score
Extent score
Stricture score
The proximal and distal segments are evaluated separately
• The total score is the sum of proximal and distal scores
• Simple, easy to learn, and has a strong inter-observer
correlation
• May serve as a convenient, reliable, and reproducible
diagnostic and follow-up tool for use by experienced
endoscopists in the evaluation of patients with CD of the small
bowel
Gal E et al. Dig Dis Sci. 2008;53(7):1933-1937.
Gralnek IM et al. Aliment Pharmacol Ther. 2008;27(2):146-154.
Gurudu SR et al. Inflamm Bowel Dis. 2009;15(10):1607-8.
Lewis Score
• Developed to assess mucosal change in the small bowel detected by
direct visualization with CE
• Objective measure of disease activity used to monitor therapy and
measure mucosal healing
• Based on Crohn’s Disease Endoscopic Index of Severity (CDEIS)
• Score provides a common language to quantify mucosal changes
associated with any inflammatory process
• Differentiates normal small bowel from diseased states
• May help establish the diagnosis of small bowel CD when combined
with other clinical signs and symptoms, including patient history,
clinical presentation, and laboratory values
• Could potentially be used to measure and document mucosal healing
in response to therapy
• Can provide one more point of evaluation with other patient data to
assist in determining appropriate disease management
Gralnek IM et al. Aliment Pharmacol Ther. 2008;27(2):146-154.
Lewis B. World J Gastroenterol. 2008;14(26):4137-4141.
Scoring Indices Key Points
• Symptom assessment is a poor indicator of severity and
extent of disease
• Clinical response does not correlate with mucosal healing or
staging of disease
• Mucosal healing may be associated with better long-term
outcomes
• Before CE there was no good direct measure of mucosal
disease activity in the small intestine
• Early clinical scoring systems were based on report of symptoms
and not on endoscopic findings or evidence of mucosal healing
• Lewis Score was developed to assess mucosal change in
the small bowel detected by direct visualization with CE
• Provides a common language to quantify mucosal changes
associated with any inflammatory process
Mucosal Healing and CE Key Points
• CE was able to detect more small bowel lesions and
monitor their healing more than would have been
possible with conventional ileocolonoscopy alone
• In a case study of a patient diagnosed with CD, serial CE
exams with Lewis Score demonstrated the utility of
monitoring response to therapy
• High diagnostic yield of CE influences disease
management and clinical outcomes
• Mucosal healing after one year of treatment is predictive
of reduced subsequent disease activity and decreased
need for active treatment
• Healing is associated with less need for hospitalization and major
abdominal surgeries