William J. Sandborn, MD
Professor of Clinical Medicine
Chief, Division of Gastroenterology
Director, UCSD IBD Center
University of California San Diego
La Jolla, California, USA
What is Mucosal Healing?
Objectives
• Describe the strengths and weaknesses of various measures of mucosal healing in ulcerative colitis
• Identify the mucosal healing rates of key therapies and combinations of treatments for ulcerative colitis
• Describe the relative value of clinical end points vs mucosal healing in following patients with ulcerative colitis See comment on application addendum
Mucosal Healing in Ulcerative Colitis
How do you Measure Mucosal Healing in Ulcerative Colitis?
• Baron score
• Mayo/Sutherland ulcerative colitis disease
activity index (UCDAI) composite instruments
with endoscopy sub-score
• Ulcerative colitis endoscopic index of severity
(UCEIS)
• Ulcerative colitis colonoscopic index of severity
(UCCIS) Baron JH. Br Med J 1964;1:89-92.
Schroeder et al. N Engl J Med 1987;317:1625-1629.
Sutherland. Gastroenterology 1987.
Travis SPL. Gut 2012;61:535-542.
Thia KT, Sandborn WJ. Inflammatory Bowel Diseases 2011;17:1257-1254.
Samuel S, Sandborn WJ. Clinical Gastroenterology & Hepatology 2012 (In Press).
Baron Score
Score Description
0 Normal: mat mucosal, ramifying vascular pattern clearly visible
throughout, no spontaneous bleeding, no bleeding to light touch
1 Abnormal but not hemorrhagic: appearances between “0” and “2”
2 Moderately hemorrhagic: bleeding to light touch, but no spontaneous
bleeding seen ahead of instrument on initial inspection
3 Severely hemorrhagic: spontaneous bleeding seen ahead of instrument at
initial inspection, and bleeds to light touch
Baron JH. Br Med J 1964;1:89-92.
Mayo Scoring System for Assessment of UC Activity
• Four components
– Stool frequency
– Rectal bleeding
– Findings of endoscopy
• 0 = Normal or inactive disease
• 1 = Mild disease (erythema, decreased vascular pattern, mild
friability)
• 2 = Moderate disease (marked erythema, absent vascular pattern,
friability, erosions)
• 3 = Severe disease (spontaneous bleeding, ulceration)
– Physicians global assessment
• Used for FDA approval of Asacol and Remicade Schroeder et al. N Engl J Med 1987;317:1625-1629.
Sutherland Index (UCDAI)
• 12 point index with 4 components
• Stool frequency (0-3)
• Rectal bleeding (0-3)
• Mucosal appearance (0-3)*
– 0 = Normal
– 1 = Mild friability
– 2 = Moderate friability
– 3 = Exudation, spontaneous hemorrhage
• Physicians global rating (0-3)
• Used for FDA approval of Rowasa and Lialda
* Modified in Lialda trials so that friability is a score of >/= 2 points
Sutherland. Gastroenterology 1987.
Ulcerative Colitis Endoscopic Index of Severity (UCEIS)
• Validated instrument
• Developed from a library of flexible sigmoidoscopy videos using different combinations of descriptors predicting the overall assessment of severity using VAS
• Three descriptors
– Vascular pattern (normal – 1, patchy obliteration – 2, obliterated – 3)
– Bleeding (none – 1, mucosal – 2, luminal mild – 3, luminal moderate or severe – 4)
– Erosions and ulcers (none – 1, erosions – 2, superficial ulcer – 3, deep
ulcer – 4)
• The score from each of the descriptors are added to calculate the UCEIS score
• The UCEIS score accounts for 90% of the overall assessment of endoscopic severity as judged by VAS (pR2=0.90)
Travis SPL. Gut 2012;61:535-542.
Ulcerative Colitis Colonoscopic Index of Severity (UCCIS)
• Validated instrument
• Developed from a library of colonoscopy videos (with 5 segments of colon scored)
using different combinations of descriptors to predict the global or segmental
assessment of endoscopic severity (GAES or SAES) or VAS
• Four descriptors
– Vascular pattern (normal – 0, partially visible – 1, complete loss – 2)
– Granularity (normal – 0, fine – 1, course - 2)
– Ulceration (normal – 0, erosions – 1, shallow – 2, deep – 3, diffuse > 30% deep - 4)
– Bleeding/friability (normal – 0, friable – 1, spontaneous bleeding – 2)
• The UCCIS score is 3.1 X vascular pattern + 3.6 X granularity + 3.5 X ulceration +
2.5 X bleeding/friability
• The UCCIS score accounts for 74-81% of the variance in the GAES score and 80-
85% of the variance in the VAS score
• Results were similar for GAES and SAES
Thia KT, Sandborn WJ. Inflammatory Bowel Diseases 2011;17:1257-1254.
Samuel S, Sandborn WJ. Clinical Gastroenterology & Hepatology 2012 (In Press).
History of the Evolution of the Endpoint of Mucosal Healing in Ulcerative Colitis
• Improvement - change by 1 point on endoscopy subscore, remission =
score of 0 points
• 2005 - Mucosal healing definition in infliximab trials –
– Inclusion criteria
• Endoscopic evidence of moderate or severe UC (endoscopy score 2) and total Mayo
score of 6-12
– Mucosal healing definition - endoscopy sub-score 0 or 1
• 2007 - Modified Sutherland (UCDAI) in MMX mesalamine trials
– Mucosal appearance
• 0 = Normal or inactive disease
• 1 = Mild disease (erythema, decreased vascular pattern, minimal granularity)
• 2 = Moderate disease (marked erythema, friability, granularity, absent vascular
pattern, bleeding minimal trauma, no ulcerations)
• 3 = Severe disease (ulcerations, spontaneous bleeding)
Rutgeerts P. NEJM 2005;353:2462-2476.
Lichtenstein GR. Clinical Gastroenterology & Hepatology 2007;5:95-102.
What are the Mucosal Healing Rates with Various Therapies in Ulcerative Colitis?
• Mesalamine
• Steroids
• Anti-TNF
– Infliximab
– Adalimumab
• Combination therapy
Delayed Release Oral Mesalamine: Mild-to-Moderate Active Ulcerative Colitis
*Mucosal healing not assessed
†Defined as “in remission” (complete resolution of all symptoms with all assessment scores = 0), OR “improved”
(reduction in PGA score and 1 other component score and no score increased) ‡P=.03 §P=.003
Sninsky CA et al. Ann Intern Med. 1991;115:350.
‡ §
* † * P
erc
en
t o
f p
ati
en
ts
Perc
en
t o
f p
ati
en
ts
Su
bje
cts
(%
)
Kamm MA et al. Gastroenterology. 2007;132:66.
Sigmoidoscopic Score of Zero at Week 8: MMX Delayed Release Mesalamine in Mild to Moderate UC
Delayed-Release Oral Mesalamine: Maintenance of Endoscopic Remission of UC
† “Maintenance of endoscopic remission at 6 months” (score of 0 out of 3 on sigmoidoscopic scale) ‡ P=.05; §P=.005.
Hanauer et al. Ann Intern Med. 1996;124:204.
Maintenance of endoscopic remission at 6 months in the per-protocol population and in the intent-to-treat population..
D’Haens GR, Sandborn WJ, et al. Am. J Gastroenterology 2012;107:1067-1077.
Per-protocol population Intent-to-treat population
Once Daily MMX Mesalamine 2.4 g for Maintenance of Endoscopic Remission in Ulcerative Colitis
Oral Cortisone: Mild-to-Severe Active Ulcerative Colitis: Mucosal Healing at 6 Weeks
*Defined as normal or near normal (slight hyperemia or granularity) mucosa
Truelove SC. Br Med J. 1954;4884:375.
P=.02
*
Infliximab Induction and Maintenance Therapy in Patients with Ulcerative Colitis: Mucosal Healing
Mucosal healing = endoscopic subscore of 0 or 1
‡
ACT 1 ACT 2
†
‡ ‡
‡ ‡
‡ ‡ ‡ ‡
†P.009 vs placebo ‡P<.001 vs placebo
Rutgeerts P et al. N Engl J Med. 2005;353:2462.
Mucosal Healing at Week 8
ACT 1 & ACT 2
*p<0.001
Rutgeerts P et al. N Engl J Med. 2005;353(23):2462-2476.
33.9
ACT 1 ACT 2
62 * 59 *
30.9
60.3 * 61.7 *
= Mayo Score of 0
= Mayo Score of 1
Mucosal Healing at Week 30
ACT 1 & ACT 2
Rutgeerts P et al. N Engl J Med. 2005;353(23):2462-2476.
24.8
ACT 1 ACT 2
50.4 * 49.2 *
30.1
46.3 †
56.7 *
= Mayo Score of 0
= Mayo Score of 1 *p < 0.001 †p = 0.009
Adalimumab Induction and Maintenance of Mucosal Healing Response at Week 8 and 52 in Ulcerative Colitis
ITT analysis set: NRI
Mucosal healing: endoscopy subscore of 0 or 1
0
10
20
30
40
Mu
co
sal
healin
g (
%)
Week 8
31.7%
50
41.1%
Week 52
15.4%
25.0%
Placebo
ADA 160/80/40 mg
p=0.032
p=0.009
Sandborn WJ, et al. Gastroenterology 2012
Infliximab, Azathioprine, or Infliximab + Azathioprine for Treatment of Moderate to Severe UC: UC SUCCESS Trial
n=28
P=0.295
P=0.028
P=0.001
28/76 42/77 49/78
37%
55% 63%
0
20
40
60
80
100
Pati
en
ts (
%)
Secondary End Point: Mucosal Healing at Week 16
Panaccione R et al. Presented at: DDW 2011; Chicago, IL; May 9, 2011. Abstract 835.
AZA
IFX
IFX + AZA
Does the Achievement of Mucosal Healing in Patients with Ulcerative Colitis Alter Clinical Outcomes?
• Steroid free remission
• Colectomy
Mucosal Healing and Time to Colectomy in Infliximab-treated Patients: Endoscopy Subscore
1 = MILD 2 = MODERATE 3 = SEVERE 0 = NORMAL
Colombel JF, Sandborn WJ, et al. Gastroenterology 2011;141:1194-1201.
Week 8 Mayo endoscopy
sub-score
Corticosteroid-free symptomatic
remission, % P value
0 46 < 0.001
1 34
2 11
3 6.5
Colombel JF. Gastroenterology 2011
Association Between Week 8 Mayo Endoscopy Sub-score and and Corticosteroid-Free Symptomatic
Remission at Week 30 During Anti-TNF Antibody Therapy
Frøslie KF, et al. Gastroenterology. 2007;133:412-422.
Pro
po
rtio
ns
of
UC
pa
tie
nts
no
t c
ole
cto
mis
ed
Time in years afer 1 year visit
1,00
0,98
0,96
0,94
0,92
0,90
0 1 2 3 4 5 76 8
Pts with MH at 1 year
Pts without MH at 1 year
p=0.02
Mucosal Healing After Treatment as Predictor of Subsequent Disease Course in Ulcerative Colitis
Mucosal Healing in Crohn’s Disease
How do you Measure Mucosal Healing in Crohn’s Disease?
• Crohn’s Disease Endoscopic Index of Severity (CDEIS)
• Simplified Endoscopic Score – Crohn’s Disease (SES-CD)
• Resolution of ulcers
• Rutgeert’s score
The Crohn’s Disease Endoscopic Index of Severity (CDEIS)
Deep
ulcerations
12 points
Superficial
ulcerations
6 points
Surface of
ulcerations
(0–10 cm)
Surface
of lesions
(0–10 cm)
Ileum 0 or 12 0 or 6 0–10 0–10
Right colon 0 or 12 0 or 6 0–10 0–10
Transverse 0 or 12 0 or 6 0–10 0–10
Left colon 0 or 12 0 or 6 0–10 0–10
Rectum 0 or 12 0 or 6 0–10 0–10
Total (sum of all cases) N
Total/number of explored segments N/1-5
+ 3 if ulcerated stenosis 0-3
+ 3 if nonulcerated stenosis 0-3
CDEIS 0 to 44
Simplified Endoscopic Score – Crohn’s Disease (SES-CD)
0 1 2 3
Presence and size
of ulcers 0.1 – 0.5 cm 0.5 – 2.0 cm > 2.0 cm
Extent of
ulcerated surface - < 10% 10% - 30% > 30%
Extent of affected
surface - < 50% 50% - 75% > 75%
Presence and
type of narrowing - single multiple
Endoscope
doesn't pass
Daperno et al. Gastrointest Endosc 2004
The score should be evaluated for the 5 segments
Rutgeerts Gastroenterology 1990
Grade Endoscopic Findings
0 No lesions in the distal ileum
1 5 aphthous lesions
2
> 5 aphthous lesions with normal mucosa between the lesions, or skip areas
of larger lesions or lesions confined to ileocolonic anastomosis
(i.e. < 1 cm in length)
3 Diffuse aphthous ileitis with diffusely inflamed mucosa
4 Diffuse inflammation with already larger ulcers, nodules, and/or narrowing
Assessment of Post-Operative Disease Recurrence: Rutgeert’s Endoscopic Scoring System
• Steroids
• Azathioprine
• Anti-TNF
– Infliximab
– Adalimumab
– Certolizumab pegol
• Combination therapy
What are the Mucosal Healing Rates with Various Therapies in Crohn’s Disese?
Change From Baseline in CDEIS
50
0
-50
-100
-150
-200
-250
-300
-350 -20 -18 -16 -14 -12 -10 -8 -6 -4 -2 0 2
Ch
an
ge F
rom
Baselin
e i
n C
DA
I
r=0.561
P=0.002
Placebo
Infliximab
Assessment Of Efficacy Of Medical Therapy: CDAI Versus CDEIS During Treatment With Infliximab
D’Haens Gastroenterology 1999
100
Rutgeerts Gastrointestinal Endosocopy 2006
Pati
en
ts D
em
on
str
ati
ng
Mu
co
sal
Healin
g (
%)
10/32 1/14 5/11 8/15 0/17
53%
46%
7%
31%
p = 0.010
p = 0.007
p = 0.026
Single Dose
Combined dose group
(5 mg/kg & 10 mg/kg
infliximab maintenance)
5 mg/kg infliximab
maintenance
10 mg/kg infliximab
maintenance
ACCENT 1 Infliximab in Active Crohn’s Disease (Naïve): Mucosal Healing at 10 and 54 Weeks in Week 2 Responders
SONIC: Mucosal Healing at Week 26
17
30
44
0
20
40
60
80
100
Pro
po
rtio
n o
f P
ati
en
ts (
%)
P<0.001
P=0.023 P=0.055
18/109 28/93 47/107
AZA + placebo
IFX + placebo
IFX + AZA
Colombel JF, et al. Infliximab, azathioprine, or combination therapy for Crohn's disease. N Engl J Med. 2010 Apr 15;362(15):1383-1395. © 2010 Massachusetts Medical Society. All rights reserved.
8/61 17/62 15/62 0/61
% o
f P
ati
en
ts P < 0.001
7/56 17/61
ITT, intention to treat; NRI, nonresponder imputation.
*NRI for missing ulceration at Weeks 12 and 52 and for missing ulceration and ulceration assessment of switched patients at
Week 52. Treatment displayed is original treatment at randomization. Analyzed using Cochran-Mantel-Haenszel test.
†Per protocol represents all ITT patients who did not have a significant protocol deviation.
Rutgeerts P, et al. Gastroenterology. 2009;136(Suppl 1):A-116.
P = 0.056 P = 0.046
†
13 13
27 28
24
0
5
10
15
20
25
30
35
40
45
50
Week 12, ITT Week 12, Per Protocol † Week 52, ITT
Adalimumab Induction Only Continuous Adalimumab
Adalimumab in Crohn’s Disease Complete Mucosal Healing at Weeks 12 and 52 NRI Analysis*
P = 0.007†
14/65 28/64 1/65
16/64
% o
f P
ati
en
ts
*NRI for missing CDEIS values at visit; ITT=129 randomized patients irrespective of presence of mucosal ulceration at screening
(as judged by review committee).
†From CMH test.
Rutgeerts P, et al. Gastroenterology. 2009;136(Suppl 1):A-116.
P < 0.001†
22
44
25
2
0
10
20
30
40
50
60
Week 12, ITT Week 52, ITT
Adalimumab Induction Only Continuous Adalimumab
Adalimumab in Crohn’s Disease CDEIS Remission at Weeks 12 and 52 (CDEIS Score ≤4): NRI Analysis*
p < 0.001*
*From analysis of covariance (ANCOVA) with treatment, CR-70 status at Week 4, and baseline value as factors. Treatment
displayed is original treatment at baseline.
SES-CD = Simplified endoscopic score-Crohn’s disease.
Rutgeerts P, et al. Gastroenterology. 2009;136(Suppl 1):A-116.
N=64 N=62 N=50 N=43 Mean
Ch
an
ge F
rom
Baselin
e
p < 0.001*
4.1
6.4
8.4
11.6
0
2
4
6
8
10
12
14
16
18
20
Week 12, ITT Week 52, ITT
Adalimumab Induction Only Continuous Adalimumab
Adalimumab in Crohn’s Disease Mean Change From Baseline in Total SES-CD
CDEIS = Crohn’s Disease Endoscopic Index of Severity Score.
Mary et al. Gut 2005;54 (Suppl. VII):A50 (OP-G-223); UCB, data on file.
61.5
42.3
11.5
0
20
40
60
80
100
Endoscopic response*, CDEIS decrease > 5
Endoscopic remission*, CDEIS < 6
Complete endoscopic remission*, CDEIS <3
% o
f p
ati
en
ts
MUSIC: Certolizumab in Active Crohn’s Disease Endoscopic Response and Remission at Week 10, N=78
What’s Wrong with Using Clinical Endpoints Rather Than Mucosal Healing?
• Clinical endpoints don’t correlate with endoscopic findings
CDAI = Crohn’s Disease Activity Index; CDEIS = Crohn’s Disease Endoscopic Index of Severity.
Modigliani R, et al. Gastroenterology. 1990;98:811-818.
0
100
200
300
400
500
600
5 10 15 20 25 30 35 0
CDAI
Correlation of CDAI vs CDEIS at D0 (n = 142) CDEIS
R = 0.13 ; NS
Crohn’s Disease Symptoms (CDAI) versus Crohn’s Disease Endoscopic Findings (CDEIS) During Treatment
with Prednisolone
IL-6 Calprotectin Lactoferrin CDAI SES-CD
hsCRP 0.65 0.47 0.52 0.16 0.46
IL-6 0.45 0.55 0.15 0.43
Calprotectin 0.76 0.23 0.45
Lactoferrin 0.19 0.48
CDAI 0.15
Correlation coefficients highlighted in red were significant (P<0.05).
When stratified by extent, correlation coefficients were highest for colonic disease.
Jones JL et al. Clin Gastroenterol Hepatol. 2008.
CDAI, Crohn’s Disease Activity Index; SES-CD, Simple Endoscopic Score for Crohn's Disease
Correlations Between hsCRP, IL-6, Fecal Markers, CDAI, and Endoscopic Activity in Crohn’s Disease (N=164)
*Unable to determine
Colombel J-F et al. N Engl J Med. 2010;362:1383-1395.
SONIC
p<0.001
p=0.003 p=0.117
p=0.927
p=0.372 p=0.688
p=0.003
p=0.139 p=0.074
16/28 13/34 6/28 12/30 12/36 11/27 68/111 50/99 35/115
Pro
po
rtio
n o
f P
ati
en
ts (
%)
Corticosteroid-Free Clinical Remission at Week 26 by Baseline Endoscopy Status
Rutgeerts Gastroenterology 1990
1
0.8
0.6
0.4
0.2% S
ym
pto
m f
ree
su
rviv
al
0 1 2 3 4 5 6 7 8
Years
i4
i3
i2
i0 + i1
Assessment Of Post-Operative Disease Recurrence: Rutgeert’s Endoscopic Scoring System
Hanauer Gastroenterology 2004
Days since baseline visit
Clinical relapse-free survival
0
0.2
50
.00
0.5
00
.75
1.0
0
200 400
Placebo
Mesalamine
6-mercaplopurine
Placebo
Mesalamine
6-mercaplopurine
600 800Days since baseline visit
Endoscopic relapse-free survival
0
0.2
50
.00
0.5
00
.75
1.0
0
200 400 600 800
6-Mercaptopurine and Mesalamine for Prevention of Post-Operative Recurrence of Crohn’s Disease
Days since baseline visit
Clinical relapse-free survival
0
0.2
50
.00
0.5
00
.75
1.0
0
200 400
Placebo
Mesalamine
6-mercaplopurine
Placebo
Mesalamine
6-mercaplopurine
600 800Days since baseline visit
Endoscopic relapse-free survival
0
0.2
50
.00
0.5
00
.75
1.0
0
200 400 600 800
Does the Achievement of Mucosal Healing in Patients with Crohn’s Disease Alter Clinical Outcomes?
• Hospitalization
• Steroid free remission
• Surgery
Rutgeerts P, et al. Gastroenterology. 2004.
Number per
100 patients
34 4 6
46
8
25
0 0 0 0
100
Number of
hospitalizations
Number of Crohn’s-related
surgeries
Patients with no healing (N=74)
Patients with healing at 1 visit (10 or 54 wks) (N=16)
Patients with healing at both visits (10 and 54 wks) (N=9)
*Endoscopic assessment at weeks 0, 10 and 54; mucosal healing was defined as the absence of mucosal ulceration
ACCENT 1: Infliximab – Hospitalization and Surgery Rate by Mucosal Healing Status
P=.0028
D’Haens G, et al. Lancet. 2008; Baert F, et al. Gastroenterology. 2010.
% o
f P
ati
en
ts
Simple endoscopic score 0
Simple endoscopic score 1-9
% o
f P
ati
en
ts in
Re
mis
sio
n
…and these patients did better in the next 2 yrs!
Steroid Avoidance Had More Endoscopic Healing at 2 Years: Secondary Endpoint of the Top-down/Step-up Trial
EXTEND: Deep Remission* Rates with Adalimumab at 1 Year
Colombel JF, Sandborn WJ, et al. J Crohn’s Colitis 2010;4:S11: OP31 at ECCO 2010
* Deep remission defined as clinical remission (CDAI <150) and complete mucosal healing in EXTEND
All patients (n=135) received adalimumab 160/80 mg induction therapy, before randomisation (n=129) to adalimumab
40 mg eow or to placebo. Deep remission was assessed in those who had ulceration at baseline (n=123).
CDAI: Crohn’s disease activity index; eow: every other week
0
5
10
15
20
25
Pati
en
ts i
n
dee
p r
em
iss
ion
* (%
)
Week 12
6/61 10/62
10
16
p=0.34
12/62 0/61
19
p<0.001
Week 52
Placebo Adalimumab 40 mg eow
Colombel JF, Sandborn WJ, et al. Gut 2010;59(Suppl 3):A80: OP371 at UEGW 2010
All-cause hospitalization
through Week 52
CD-related hospitalization
through Week 52
17
0
5
10
15
20
0/11 9/53 All h
osp
italizati
on
(%
)
9
0
5
20
0/11 5/53 C
D-r
ela
ted
ho
sp
italizati
on
(%
) Deep
remission*
(Week 12)
Non-deep
remission*
(Week 12)
Deep
remission*
(Week 12)
Non-deep
remission*
(Week 12)
10
15
* Deep remission defined as clinical remission (CDAI <150) and complete mucosal healing in EXTEND
CD: Crohn’s disease; CDAI: Crohn’s disease activity index
EXTEND: Patients who Achieved Deep Remission* with Adalimumab at Week 12 And Hospitalization Rates
MH = mucosal healing.
Frøslie KF, et al. Gastroenterology. 2007;133:412-422.
Pts with MH at 1 year
Patients without MH at 1 year
Pro
po
rtio
n o
f C
D p
ati
en
ts n
ot
rese
cte
d
0.6
0.7
0.8
0.9
1.0
0 1 2 3 4 5 6 7
Time in years after 1 year visit
Mucosal Healing After Treatment as Predictor of Subsequent Disease Course in Crohn’s Disease
Mucosal Healing Predicts Long-term Outcome of Maintenance Therapy with Infliximab in CD
Schnitzler F, et al. Inflamm Bowel Dis. 2009.
Sustained clinical benefit long-term with respect to mucosal healing during
IFX treatment
1.0
0.0 0
Proportion of patients with sustained clinical benefit (%)
12 24 36 48 60 72 84 96 Follow-up since first IFX (months)
At risk: 75 67 52 41 26 19 15 10 4 27 23 17 14 11 7 3 2 2
Breslow: P=.239
LogRank: P=.058
Mucosal healing (N=75) No mucosal healing (N=27)
Need for major abdominal surgeries by degree of mucosal healing
(median 22.3 months follow-up)
40
0 Complete mucosal healing (N=85)
Partial mucosal healing (N=43)
No mucosal healing (N=86)
Patients needing surgery (%)
14.1% 14%
38.4%
P<.0001
12/85 6/43 33/86
Conclusions
• Mucosal healing
– Is measurable
– Is achievable
– May
• Increase steroid free remission
• Reduce hospitalization
• Reduce surgery
