1. How Should We be Assessing and Documenting Endoscopies in IBD: Incorporating Standard Scoring Systems into Patient Care
Gary R Lichtenstein, MD
Director, Center for IBD
University of Pennsylvania School of Medicine
Hospital of the University of PA
Philadelphia, PA

2. Uses of Endoscopy in IBD
Diagnosis
Disease extent
Prognostication
Assessment of Activity/Healing
Stricture evaluation and dilation
Dysplasia Surveillance
Diagnose/Control Bleeding
Pouch Evaluation
Endoscopic Ultrasound
Video Capsule Endoscopy

3. I. Mucosal Healing
UC and Crohn’s disease characterized by the presence of gut inflammation accompanied by areas of ulceration
Mucosal healing is becoming increasingly important in the clinical management of UC and Crohn’s disease, as well as being used as an end point in clinical trials.
Achieving mucosal healing has unequivocally been associated with better outcomes, and for these reasons, it has become an important treatment goal.

4. I. Mucosal Healing
Multiple methods to score endoscopic disease activity in both UC and Crohn’s disease.
Those used most frequently or that have been validated:
Mayo Endoscopic Score
Ulcerative Colitis Endoscopic Index of Severity (UCEIS)
Crohn’s Disease Endoscopic Index of Severity (CDEIS),
Simple Endoscopic Score for Crohn’s Disease (SES-CD),
Rutgeerts Postoperative Endoscopic Index for Crohn’s disease.

5. II. Definition of Mucosal Healing
Mucosal healing in the context of IBD refers to the endoscopic assessment of disease activity.
Simply stated, mucosal healing should imply the absence of ulceration and erosions.
There is currently no validated definition of mucosal healing in IBD.

6. III. Inflammation in UC
The pattern of inflammation in UC is associated with several mucosal changes, initially
vascular congestion,
erythema, and
granularity.
As inflammation becomes more severe,
friability (bleeding to light touch),
spontaneous bleeding, and
erosions and
ulcers develop.

7. What Is the Definition of Mucosal Healing?

8. AGA Consensus on Efficacy End Points: Endoscopic Healing in Ulcerative Colitis
“Absence of friability, blood, erosions, and ulcers in all visualized segments are the required components of genuine endoscopic healing.”
D’Haens G et al. Gastroenterology 2007;132(2):763–86. 8

9. Mucosal Healing in Ulcerative Colitis Disease: The Issues
What is the definition of mucosal healing?
Depends on finding a scoring system of your choice
some studies allow erythema and friability in the
definition of mucosal healing 1
Many different endoscopic indices for UC have been
used in clinical trials, only one UCEIS - validated in prospective studies; this creates problems when comparing trials.
1.) Dave M, et al Gastroenterol Hepatol 2012;8(1):29–38. 9

10. Mucosal Abnormalities in Crohn’s Disease
The SB has limited ways to demonstrate injury:
Mucosal Disruption
Erosions
Ulcers
Erythema
Villous Blunting
Strictures
These findings are easily captured by capsule endoscopy, but are not pathognomonic of IBD.

11. Hypothesis Erythema and Villous Blunting Aphthous Ulcers VCE +
Superficial Ulceration
Serpiginous or Linear Ulcers
Rad +
Cobblestone Appearance
Transmural Inflammation
Strictures, Fistulas
Carucci LR et al: GI Clinics NA 31:93-117, 2002

12. What Is the Definition of Mucosal Healing in Crohn’s Disease?
CDEIS: Deep ulceration, superficial ulceration, and inflammation1
Complex (many variables and scores range from 0 to 44)
Experience is required
Difficult to use in clinical practice
No validated definition of mucosal healing
SES-CD: Ulcers, inflammation, and narrowing2
Validated in only 1 study
Scores range from 0 to 60
Rutgeerts Score: Aphthoid lesions, inflammation, ulcers, nodules, and narrowing3
Only applicable to postoperative recurrence
No endpoint for endoscopic remission in the trials
CDAI = Crohn’s Disease Activity Index; SES-CD = Simple Endoscopic Score for Crohn's Disease. 1. Mary JY et al. Gut. 1989;30: ; 2. Daperno M et al. Gastroenterology. 2002;122:A216; 3. Rutgeerts P et al. Gastroenterology. 1990;99: 12

13. Limitations of Endoscopic Scores of Bowel Lesions in Crohn’s Disease?
No validated endpoints for:
Endoscopic response
Endoscopic remission
Complete mucosal healing = total disappearance of all ulcers
Does the mucosal activity reflect transmural damage?
No controlled studies have evaluated endoscopic score correlation with the entire thickness of the intestinal wall
What is the spontaneous variation of endoscopic activity in Crohn’s disease?
Study of the placebo effect 13

14. Limitations of Endoscopic Scores of Bowel Lesions in Crohn’s Disease?
Does not access small bowel other than terminal ileum
Makes assumption that changes to the lesions in terminal ileum reflect what transpires in remainder of the small bowel 14

15. Actual Endoscopic Indices
Ulcerative Colitis
Mayo Score
UCIEIS
Crohn’s Disease
UCEIS
SES-CD
Rutgeerts Score 15

16. UC Endoscopic Indices
Table Source- Walsh A, et al. Gastrointest. Endoscopy Clin. N. Am. 2014; 24: 367–378 16

17. Mayo Scoring System1 for Assessment of UC Activity
Stool frequency: 0 = Normal number of stools for this patient
1 = 1 to 2 stools more than normal
2 = 3 to 4 stools more than normal
3 = 5 or more stools more than normal
Rectal bleeding: 0 = None
1 = Streaks of blood with stool less than half the time
2 = Obvious blood with stool most of the time
3 = Blood alone passes
Endoscopic findings: 0 = Normal or inactive disease
1 = Mild disease (redness, decreased vascular
pattern visible, friability)
2 = Moderate disease (redness, no vascular
pattern visible, friability, erosions)
3 = Severe disease (bleeding, ulceration)
Physician’s global assessment of disease activity: 0 (normal) to 3 (severe)
Schroeder KW, et al. N Engl J Med. 1987;317(26):

18. Mayo Score: Practical Points
Overlap in the features of the different levels of this endoscopic index, which causes high interobserver variation.
The most troublesome component of this index is friability, as this is subjective and leads to inconsistent results.1
This inconsistency has lead to an adaptation of the index to remove friability. 2,3
1.) D’Haens G, et al Gastroenterology2012;143(6):1461–9.
2.) Kamm MA, et al. Gastroenterology2007;132(1):66–75.
3.) Lichtenstein GR, et al Clinical Gastroenterol Hepatol. 2007; 2007;5: 95–102. 18

19. Mayo Score: Practical Points
The value of this index is its widespread use in clinical trials.
Mucosal healing – 0 or 1- or a deceases from the subscores of 2 or 3.1
In Active Ulcerative Colitis Trials, patients with a post-treatment Mayo score of grade 1 were no more likely to undergo a colectomy than those with a score of 0. 1
1.) Rutgeerts P , et al N Engl J Med 2005;353(23):2462–76. 19

20. UCEIS for Assessment of UC Activity
Table Source- Walsh A, et al. Gastrointest. Endoscopy Clin. N. Am. 2014; 24: 367–378

21. UCEIS: Practical Points
In practical terms, the most severely affected part of the mucosa is scored.
Limitations-
Thresholds for remission and mild, moderate, and severe disease have yet to be set.
The extent to which full colonoscopy may influence the score compared with the flexible sigmoidoscopy on which it was based, has only started to be evaluated .1
1- Thia KT et al, Inflamm Bowel Dis. 2011;17(6):1257–64. 21

22. UCEIS: Practical Points
Knowledge of symptoms does not materially influence the score, and a comparison with the Mayo Clinic endoscopy subscore shows that the UCEIS is less subject to variation by a central reader.
UCEIS is simple enough to use in clinical practice and should achieve its goal of reducing variation in endoscopic assessment of activity between observers.
Patients admitted with acute severe colitis with a score of 7 or 8 (out of 8) on admission predicted an inadequate response to intravenous steroids and the need for rescue therapy with cyclosporine or infliximab1.
Easy for in office use
1.) Conte CJ, et al. Gastroenterology 2013; 144(5): S-102. 22

23. Crohn’s Disease: Endoscopy
Table Source- Walsh A, et al. Gastrointest. Endoscopy Clin. N. Am. 2014; 24: 367–378 23

24. Crohn’s Disease Endoscopic Index of Severity
Prospectively developed instrument constructed to detect changes in disease activity1.
Examines 4 endoscopic variables
In each of the following locations: rectum, sigmoid and left colon, transverse colon, and right colon and ileum
CDEIS scores range from 0 to 44.
Mary JY, et al. Gut 1989;30(7): 983–9. 24

25. Crohn’s Disease Endoscopic Index of Severity
CDEIS Evaluates:
Deep ulcerations: score 0 if absent or 12 if present.
Superficial ulcerations: score 0 if absent or 6 if present.
Length of ulcerated mucosa (0-10cm): score 0 to 10 according to length in centimeters
Length of diseased mucosa (0-10cm): score 0 to 10 according to length in centimeters.
1.) Conte CJ, et al. Gastroenterology 2013; 144(5): S-102
. 25

26. Crohn’s Disease Endoscopic Index of Severity
The numbers are added up in each segment and divided by the number of segments evaluated.
An additional 3 points is given if an ulcerated stenosis is present, and a further 3 points if a nonulcerated stenosis is present.
Mary JY, et al. Gut 1989;30(7): 983–9. 26

27. Crohn’s Disease Endoscopic Index of Severity
Table Source- Walsh A, et al. Gastrointest. Endoscopy Clin. N. Am. 2014; 24: 367–378 27

28. Crohn’s Disease Endoscopic Index of Severity
CDEIS Definitions:
Endoscopic remission (minor or no lesions) is defined as a CDEIS score less than or equal to 6 or less than or equal to 7
Complete endoscopic remission (mucosal healing, i.e., no lesions at all or scarred lesions only) is defined as a CDEIS score less than or equal to 3 or less than or equal to 4.
Endoscopic response is a decrease from baseline CDEIS score of at least 4 or 5 points.
.
Mary JY, et al. Gut 1989;30(7): 983–9. 28

29. Crohn’s Disease Endoscopic Index of Severity
Critque:
It is the standard index and it is reproducible.
It is complex
Requires training and experience
To estimate ulcerated or disease mucosal surface areas
To distinguish between superficial and deep ulcerations.
It is cumbersome to use in clinical practice.
Mary JY, et al. Gut 1989;30(7): 983–9. 29

30. Simplified Endoscopic Score for Crohn’s Disease
Daperno M, et al. Gastrointest Endoscopy 2004; 60: 30

31. Crohn’s Disease Endoscopic Index of Severity
Critque:
The SES-CD correlates well with the CDEIS
Correlation coefficient (r=0.920)
Interobserver reliability (kappa )
Easy to use
Less complex than the CDEIS
No cutoff values have been determined for this
Mucosal healing not defined.
Daperno M, et al. Gastrointest Endoscopy 2004; 60: 31

32. The Natural Course of Postop CD
Recurrence is clinically silent initially
Histologic
Endoscopic
Radiologic
Clinical
Surgical
30% 3 yr
60% 5 yr
Within
1 week
70-90%
by 1 yr
Tissue damage
50% by 5 yrs
Surgery
[1] D’Haens G, Geboes K, Peeters M, et al. Gastroenterology 1998;114:
[2] Olaison G, S medh K, Sjodahl R. Gut 1992;33:
[3] Rutgeerts P, Geboes K, Vantrappen G, et al Gastroenterology 1990;99:
[4] Sachar DB. Med Clin North Am 1990;74:

33. Endoscopic Recurrence Score
Endoscopic Remission
i0: no lesions
i1: < 5 aphthous lesions
i2: > 5 aphthous lesions with normal intervening mucosa
i3: diffuse aphthous ileitis with diffusely inflamed mucosa
i4: diffuse inflammation with large ulcers, nodules, and/or narrowing
Endoscopic Recurrence
Rutgeerts P, Geboes K, Vantrappen G, et al Gastroenterology 1990;99:

34. >70% of Pts Have i2,3,4 Recurrence 1 Year after Surgery – Rutgeerts et al Gastro 1990
i0 and i1 remission
-low likelihood of progression
i,3 i4
i2,i3,i4 recurrence
Likely progression
to another surgery

35. Actuarial Rate of Symptomatic Recurrence
Those individuals with grade 3 and 4 lesions at one year postoperatively during
colonoscopy were more likely to have symptomatic recurrences earlier than
those with individuals with grade 1 and 2 lesions.
1.0
Grade 0 and Grade 1
0.8
% symptom free survival
0.6
Grade 2
0.4
0.2
Grade 4
Grade 3 1 1 2 3 4 5 6 7 8 9 10
Rutgeerts P, Geboes K, Vantrappen G, et al Gastroenterology 1990;99:

36. POCER Study: Postoperative Crohn’s Disease Endoscopic Recurrence
Methods: Multicentre RCT
No Endoscopy (“Standard”)
Risk driven best drug therapy
1/3 of patients
All patients: Metronidazole: 0-3 months
Randomization
Low risk: No further treatment
High risk: Thiopurine or adalimumab if thiopurine intolerant
18 Month Colonoscopy
RISK Stratification:
Low or High
(High risk: smoker,
≥ second operation,
perforating disease)
2/3 of patients
6 Month Colonoscopy
Step up Rx if ≥ i2 on Rutgeerts scale
Endoscopic Intervention
(“Active”)
SURGERY: Curative resection
De Cruz P, et al. Presented at DDW; May Abstract 925J.

37. POCER Study: Postoperative Crohn’s Disease Endoscopic Recurrence
Results:
32% dropout rate; no difference between both study arms
174 randomized: 122 Active/ 52 Standard
6-month (short-term) endoscopic recurrence: ADA better than thiopurine in high-risk patients (P=0.028)
Stepping up at 6 months if ≥i2 brought 39% into endoscopic remission at 18 months
Remission at 6 months colonoscopy, 39% endoscopic recurrence at 18 months
Conclusions regarding postoperative recurrence of Crohn’s:
Treatment according to risk of recurrence at 6 month colonoscopy, is superior to drug therapy alone
Step-up with anti-TNF therapy, based on colonoscopy findings at 6 months, is a viable strategy in high-risk patients
Rutgeerts ≤ i2 at 18 months
Active Care (n=122)
62/122 (51%)
P= 0.028
Standard Care (n=52)
17/52 (33%)
Adalimumab Immediately Postop (n=28)
16/28 (57%)
P = 0.2
Adalimumab Initiated if i≥2 at 6 Months (n=32)
13/32 (41%)
De Cruz P, et al. Presented at DDW; May 21, Abstract 925J.

38. CONCLUSION
The colonoscopic assessment of mucosal inflammation and healing is important for assessment of patients with UC and CD
All clinicians should try to achieve mucosal healing in patients with IBD
Multiple endoscopic indices for UC exist but only one, the UCEIS is validated
The CDEIS and SES-CD are validated in CD
The Rutgeerts postoperative endoscopic index is useful for predicting the clinical course in patients with ileocecal CD undergoing ileocecal resections 38