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Inflammatory Bowel Inflammatory Bowel DiseaseDisease
DefinitionDefinition
Inflammatory bowel disease (IBD) is a term Inflammatory bowel disease (IBD) is a term encompassing a number of chronic encompassing a number of chronic inflammatory disorders leading to damage of inflammatory disorders leading to damage of the gastrointestinal tract. the gastrointestinal tract.
Crohns diseaseCrohns disease
Symptoms of CDSymptoms of CD
The presentation depends on the site, extent, severity, and The presentation depends on the site, extent, severity, and complications of intestinal and extraintestinal disease.complications of intestinal and extraintestinal disease.
Fevers, night sweats, and weight loss.Fevers, night sweats, and weight loss.
Abdominal pain Abdominal pain
Nausea and vomiting Nausea and vomiting
DiarrheaDiarrhea
Rectal bleedingRectal bleeding
Extraintestinal Manifestations of Extraintestinal Manifestations of
Inflammatory Bowel DiseaseInflammatory Bowel Disease MusculoskeletalMusculoskeletal
Peripheral arthritis Peripheral arthritis Sacroiliitis Sacroiliitis Ankylosing spondylitis Ankylosing spondylitis OsteoporosisOsteoporosis
DermatologicDermatologic Erythema nodosum Erythema nodosum Pyoderma gangrenosum Pyoderma gangrenosum Aphthous stomatitisAphthous stomatitis
Hepatobiliary DiseaseHepatobiliary Disease Primary sclerosing cholangitisPrimary sclerosing cholangitis
OcularOcular Uveitis Uveitis Scleritis Scleritis EpiscleritisEpiscleritis
VascularVascular Thromboembolic eventsThromboembolic events
RenalRenal NephrolithiasisNephrolithiasis
Physical Examination in CDPhysical Examination in CD
Weight loss and pallor.Weight loss and pallor. Clubbing of the fingers.Clubbing of the fingers. Abdominal distension Abdominal distension
Tenderness in the area of involvement Tenderness in the area of involvement
Abnormal bowel sounds. Abnormal bowel sounds.
Presence of an inflammatory mass are common. Presence of an inflammatory mass are common.
Perianal abscess, fistula, skin tags, or anal stricture.Perianal abscess, fistula, skin tags, or anal stricture.
Laboratory StudiesLaboratory Studies
AnemiaAnemia Deficiencies of iron, vitamin B12, or folic acid Deficiencies of iron, vitamin B12, or folic acid Anemia of chronic disease. Anemia of chronic disease.
LeukocytosisLeukocytosis ThrombocytosisThrombocytosis Elevated ESR and C-reactive protein levels Elevated ESR and C-reactive protein levels Decreased Serum albumin levels Decreased Serum albumin levels Urinalysis commonly demonstrates calcium oxalate crystals.Urinalysis commonly demonstrates calcium oxalate crystals. Stoolanalysis for fecal leukocytesStoolanalysis for fecal leukocytes Serologic markers with high specificity for CD.Serologic markers with high specificity for CD.
Anti-Anti-Saccharomyces cerevisiaeSaccharomyces cerevisiae antibody(ASCA) antibody(ASCA) Antibody to the outer core membrane of Antibody to the outer core membrane of E. coliE. coli (OmpC) (OmpC)
Imaging StudiesImaging Studies
Plain abdominal x- rayPlain abdominal x- ray Barium studiesBarium studies
Small bowel enema (enteroclysis) / follow-throughSmall bowel enema (enteroclysis) / follow-through Large bowel enemaLarge bowel enema
U/S Abdomen and Pelvis / Transrectal U/SU/S Abdomen and Pelvis / Transrectal U/S CT Abdomen and PelvisCT Abdomen and Pelvis MRIMRI
CDCD
Aphthoid ulceration of terminal ileum (small arrows)- Note also "cobblestoning" (larger arrows).
Typical features of Crohn's disease of the distal ileum including fissure ulcers (small arrows), longitudinal ulcers (arrowhead), "cobblestoning" (open arrows), aphthoid ulcers (curved arrow) and stricturing. ic=ileocaecal valve.
EndoscopyEndoscopy
Upper and Lower EndoscopyUpper and Lower Endoscopy Capsule EndoscopyCapsule Endoscopy
CDCD
CDCD
CDCD
Granuloma in CDGranuloma in CD
ACG Practice Guidelines:ACG Practice Guidelines:Definitions of Disease SeverityDefinitions of Disease Severity
Ambulatory patientsAmbulatory patients Patients who are able to tolerate oral alimentationPatients who are able to tolerate oral alimentation Patients without manifestations ofPatients without manifestations of
DehydrationDehydration Toxicity ( high fever, rigors, prostration )Toxicity ( high fever, rigors, prostration ) Abdominal tendernessAbdominal tenderness Painful massPainful mass Obstruction Obstruction >10% weight loss>10% weight loss
Mild – Moderate CD :
Hanauer et al A J Gastroenterology 2001,96,635
ACG Practice Guidelines:ACG Practice Guidelines:Definitions of Disease Severity (cont.)Definitions of Disease Severity (cont.)
Patients who have failed to respond to treatment Patients who have failed to respond to treatment for mild-moderate diseasefor mild-moderate disease
Patients with more prominent symptom of:Patients with more prominent symptom of: FeverFever Significant weight lossSignificant weight loss Abdominal pain or tendernessAbdominal pain or tenderness Intermittent nausea or vomiting (Intermittent nausea or vomiting (without without
obstructive findingsobstructive findings)) Significant anemiaSignificant anemia
Moderate-Severe CD:
Hanauer et al A J Gastroenterology 2001,96,635
ACG Practice Guidelines:ACG Practice Guidelines:Definitions of Disease Severity (cont.)Definitions of Disease Severity (cont.)
Patients with persistent symptoms despite the Patients with persistent symptoms despite the introduction of steroids as out patientintroduction of steroids as out patient
Individuals presenting with: Individuals presenting with: High feverHigh fever Persistent vomitingPersistent vomiting Evidence of intestinal obstructionEvidence of intestinal obstruction Rebound tenternessRebound tenterness CachexiaCachexia, or, or Evidence of Evidence of abscessabscess
Sever –Fulminant CD:
Hanauer et al A J Gastroenterology 2001,96,635
ACG Practice Guidelines:ACG Practice Guidelines:Definitions of Disease activityDefinitions of Disease activity
Patients who are asymptomatic or without Patients who are asymptomatic or without inflammatory sequelaeinflammatory sequelae
Patients who have responded to acute medical Patients who have responded to acute medical interventionintervention oror have udergone surgical resection have udergone surgical resection without gross evidence of residual diseasewithout gross evidence of residual disease
NB:NB: Patients requiring steroids to maintain well-being are Patients requiring steroids to maintain well-being are considered to be “steroid-dependen”and are usually considered to be “steroid-dependen”and are usually notnot cosidered to be “in remission.” cosidered to be “in remission.”
CD in remission:
Hanauer et al A J Gastroenterology 2001,96,635
Long-term disease evolution Long-term disease evolution behavior in CDbehavior in CD
penetrating
stricturing
0
10
20
30
40
50
60
70
80
90
100
0 12 24 36 48 60 72 84 96 108 120 132 144 156 168 180 192 204 216 228 240
Months
cu
mu
lati
ve
pro
ba
bili
ty(%
)
inflammatory
Cosnes J et al. Inflamm Bowel Dis 2002;8;244
Medical treatment of IBDMedical treatment of IBD
Yousef A. Qari Yousef A. Qari MD,FRCPC,ABIMMD,FRCPC,ABIM
Consultant GastroenterologistConsultant GastroenterologistKing Abdulaziz University HospitalKing Abdulaziz University Hospital
Jeddah, Saudi Arabia Jeddah, Saudi Arabia
Current Expectations for IBD TherapyCurrent Expectations for IBD Therapy
Induce clinical remissionInduce clinical remission Maintain clinical remissionMaintain clinical remission Improve quality of lifeImprove quality of life
PlusPlus Heal mucosaHeal mucosa Decrease hospitalization / surgery / overall costsDecrease hospitalization / surgery / overall costs Minimize disease- related and therapy-related Minimize disease- related and therapy-related
complicationscomplications
ACG Practice Guidelines:ACG Practice Guidelines:Recommended treatmentRecommended treatment
AminosalicylatesAminosalicylates Sulphasalazine (3-6g/d)Sulphasalazine (3-6g/d) Mesalamine (3.2-4.0g/d) Mesalamine (3.2-4.0g/d) 40-50%40-50%
Antibiotics (CD involving colon)Antibiotics (CD involving colon) Metronidasole (10-20mg/kg) 50%Metronidasole (10-20mg/kg) 50% Ciprofloxacin (1g/d)Ciprofloxacin (1g/d) Metro+Cipro (250mg 2-3 times/d +500mg 2 times/d) Metro+Cipro (250mg 2-3 times/d +500mg 2 times/d) 76%76%
Budesonide (CIR) (9mg/d)Budesonide (CIR) (9mg/d) For ileal & Rt colonic disease For ileal & Rt colonic disease 69%69%
Mild – Moderate CD :
Remission
ACG Practice Guidelines:ACG Practice Guidelines:Recommended treatmentRecommended treatment
CorticosteroidsCorticosteroids Appropriate antibiotics therapy or drainageAppropriate antibiotics therapy or drainage
(surgical/percutaneous) required for infection (surgical/percutaneous) required for infection or abscessor abscess
InflximabInflximab infusion infusion Effective adjunctEffective adjunct Possible alternative to steroid therapy in selected Possible alternative to steroid therapy in selected
patients in whom corticosteroids are patients in whom corticosteroids are contraindicated or ineffective.contraindicated or ineffective.
Moderate –Severe CD
Oral Budesonide for active CDOral Budesonide for active CD
0
10
20
30
40
50
60
(n=66) 3mg (n=67) 9mg(n=61) 15mg(n=64)
placebo Budesonide
Pat
ien
ts i
n r
emis
sio
n(%
)
2 wk
4 wk
8 wk
Greenberg etal . N Engl J Med 1994;331;836-41
ACG Practice Guidelines:ACG Practice Guidelines:Recommended treatmentRecommended treatment
CorticosteroidsCorticosteroidsBudesonide 9mg/d Budesonide 9mg/d ororPrednisone (0.5-0.75mg/kg) Prednisone (0.5-0.75mg/kg) or or 40mg/d40mg/d
5o-70% remission rate in 8-12 weeks5o-70% remission rate in 8-12 weeks Until resolution of symptoms and resumption of weight Until resolution of symptoms and resumption of weight
gain, generally 7-28 days.gain, generally 7-28 days. Steroid refractory & steroid dependent ≈ 50%Steroid refractory & steroid dependent ≈ 50%
SmookingSmooking Colonic diseaseColonic disease
Not Not effective for maintenanceeffective for maintenance
Moderate –Severe CD:
Clinical response and remission in Infliximab-Clinical response and remission in Infliximab-treated patientstreated patients
17
4
48
81
0
25
50
75
100
4-weeks clinicalresponse
4-weeks clinicalremission
% p
ati
en
ts placebo(n=25)
Infliximab5mg/kg(n=27)
Clinical response : ≥70 points decrease in CDAI from baseline
Clinical remission : a CDAI of < 150
Targan SR et al, N Engl J Med. 1997:337:1029
Moderate-Severe CD:
Clinical Response at Week 52*Clinical Response at Week 52*
53
43
17
0
10
20
30
40
50
60
70
80
90
100
Single dose(n=110)
5mg/kg Q8w (n=113)
10mg/kg Q8w
(n=111)
Pro
po
rtio
n o
f p
atie
nts
(%)
P<0.001
P<0.001
P=NS
*Week-2 Responders
Clinical Remission at Week 54*Clinical Remission at Week 54*
38
28
14
0
10
20
30
40
50
60
Pro
po
rtio
n o
f P
ati
en
ts(%
)
Single dose(N=110)
5mg/kgQ 8w
(N=113)
10mg/kgQ 8w
(N=112)
P<0.007
P<0.001
P=NS
*Week-2 Responders
ACG Practice Guidelines:ACG Practice Guidelines:Recommended treatmentRecommended treatment
Hospitalization required for :Hospitalization required for : patients with persistent symptoms despite introduction of oral patients with persistent symptoms despite introduction of oral
steroids or infliximabsteroids or infliximab
Patients presenting with high fever, frequent vomiting, evidence Patients presenting with high fever, frequent vomiting, evidence of intestinal obstruction, rebound tenderness, cachexia, or an of intestinal obstruction, rebound tenderness, cachexia, or an abscessabscess
Surgical consultation is warranted for patients with Surgical consultation is warranted for patients with obstruction or tender abdominal mass.obstruction or tender abdominal mass.
Severe-Severe-Fulminant CD:Fulminant CD:
Hanaur S et al. Am J Gastroenterology; 96; 635
ACG Practice Guidelines:ACG Practice Guidelines:Recommended treatmentRecommended treatment
Exclude abscessExclude abscess Abd USAbd US Abd CTAbd CT
Parentral corticosteroids equivalent to Parentral corticosteroids equivalent to 40-60mg prednisone40-60mg prednisone If abscess has been excludedIf abscess has been excluded If the patient has been receiving oral setroidsIf the patient has been receiving oral setroids
Severe-Severe-Fulminant CD:Fulminant CD:
Drainage
PercutaneousSurgical
ACG Practice Guidelines:ACG Practice Guidelines:Recommended treatmentRecommended treatment
Parentral broad spectrum antibioticsParentral broad spectrum antibiotics High feverHigh fever Toxic appearanceToxic appearance Inflammatory massInflammatory mass
Nutritional support: (Elemental or TPN)Nutritional support: (Elemental or TPN) TPN in addition to steroids plays no specific roleTPN in addition to steroids plays no specific role IndicationsIndications
For patients unable to maintain nutritional requirments For patients unable to maintain nutritional requirments after 5-7 daysafter 5-7 days
Preoperative managementPreoperative management Pediatric age groupsPediatric age groups
Severe-Severe-Fulminant CD:Fulminant CD:
Therapeutic Options for Therapeutic Options for Perianal Fistulas in CDPerianal Fistulas in CD
Possible efficacyPossible efficacy Antibiotics Antibiotics AZT/6-MP AZT/6-MP
CyclosporineCyclosporine
Proven efficacyProven efficacy InfliximabInfliximab
Therapeutic Options forTherapeutic Options for Perianal Fistulas in CD Perianal Fistulas in CD
AZT/6-MP
21
54
0
10
20
30
40
50
60
70
80
90
100
Placebo AZT/6-MP
% p
atie
nts
with
Fis
tula
re
spo
nse
6/29 22/41
Compleate healing or decreased discharge΅
Pearson DC et al. Ann Intern Med.1995;122;132
Therapeutic Options forTherapeutic Options for Perianal Fistulas in CD Perianal Fistulas in CD
38
55
13
0
20
40
60
80
100
Placebo Infliximab 5 mg/kg
Infliximab10 mg/kg
% p
atie
nts
with
com
plea
t c
losu
re o
f al
l Fis
tula
s
%
%
%
Infliximab
Present DH et al. N Engl J Med. 1999;34;1398
P=0.001
P=0.04
Newly Diagnosed Crohn (N = 129)
Step-up (N = 64)
steroids
Top-down (N = 65)
IFX (0/2/6) + AZA
steroids
steroids
+ AZAMTX
+ IFX IFX + AZA
+ (epis) IFX
steroids
Step-up versus Top-down TrialStep-up versus Top-down Trial
relapserelapse
Step Up treatment paradigm driven by Step Up treatment paradigm driven by cost, safety and adverse eventscost, safety and adverse events
Aminosalicylates
SteroidsElemental dietAntibiotics
Infliximab
Immunosuppressives
The classical Step-Up-treatment paradigm
Surgery
Azathioprine is the best conventional Azathioprine is the best conventional drug to maintain clinical remissiondrug to maintain clinical remission
80
60
40
20
0
Placebo (n=30)
AZA 2.5 mg/kg per d (n=33)80
60
40
20
0
Placebo (n=30)
AZA 2.5 mg/kg per d (n=33)80
60
40
20
0
Placebo (n=30)
AZA 2.5 mg/kg per d (n=33)
% P
atie
nts
No
t F
aili
ng
Tri
al
Duration of Trial (Months)
Candy S et al. Gut. 1995;37:674.
0 15
Remission induced by prednisolone; tapered over 12 wk
100
ster +AZA AZA
Continuous Immunotherapy is Continuous Immunotherapy is required to treat a Chronic Diseaserequired to treat a Chronic Disease
0.0
0.2
0.4
0.6
0.8
1.0
0 6 12 18
Months After Randomization
Per
cent
age
of P
atie
nts
in
Rem
issi
on
Azathioprine
Placebo
Remission (months)mean ± SE17.3 ± 0.515.9 ± 0.7
% relapse
7.9
21.3
Lemann et al. Gastroenterol. 2005 Jun;128(7):1812-8.
Months after randomisation
Patients in clinical remission with AZA for at least 3.5 years before randomisation
Cumulative Probability of Cumulative Probability of Surgical Intervention in CDSurgical Intervention in CD
Munkholm P et al. Gastroenterology. 1993; 105:1716.
Years
Pro
babi
lity
(%)
Events (no.) 122 26 15 7 7 4 8 1 8 2 2 2 3 2 1
0
20
40
60
80
100
0 2 5 8 11 14 17 20
± 2 SD
Dx
Ulcerative colitisUlcerative colitis
DifinitionDifinition
A chronic disease charecterized by diffuse A chronic disease charecterized by diffuse mucosal inflammation limited to the colon. mucosal inflammation limited to the colon.
Age distribution of Ulcerative colitis in east and west Age distribution of Ulcerative colitis in east and west provinces of Saudi arabia provinces of Saudi arabia 188 CASES188 CASES
0
10
20
30
40
50
60
70
80
Less than 20 20-49 50 and above
West SA
East SA
Age(y) at presentation
1. Qari Y et al, under publication
2. Satti M et al, Ann Saudi Med 1996;16(6):637-640.
Sex distribution of UC in the GulfSex distribution of UC in the Gulf
0
10
20
30
40
50
60
70
80
Male Female
west SA(1)
Cent SA(2)
East SA(3)
Kuwait(4)
Iran(5)
1. Qari Y et al, under publication2. Hossain J et al. Ann Saudi Med 1991;11:40-6.3. Satti M et al, Ann Saudi Med 1996;16(6):637-
640.
4. Al-Nakib B et al. Am J Gastroenterology 1984;79:191-4 5. Mir-Madjlessi SH et al. Am J Gastroenterology 1985;11:862-6.
Pattern of UC in the GulfPattern of UC in the Gulf
0
10
20
30
40
50
60
70
80
90
100
Pancolitis Left colitis
West SA(1)
Cent SA(2)
East SA(3)
Kuwait(4)
Iran(5)
1. Qari Y et al, under publication
2. Hossain J et al. Ann Saudi Med 1991;11:40-6.
3. Satti M et al, Ann Saudi Med 1996;16(6):637-640.
.
4. Al-Nakib B et al. Am J Gastroenterology 1984;79:191-4 5. Mir-Madjlessi SH et al. Am J Gastroenterology 1985;11:862-6.
Epidemiological figures comparing Epidemiological figures comparing East vs WestEast vs West
Geographic location Gulf Region
Saudi Arabia
West Europe
and USA
Incidence 0.5 – 2.8 / 100 000 6 -8 / 100 000
Prevalence ≈ 5 / 100 000 70 -150 /100 000
Ulcerative colitisUlcerative colitis
UC NormalUC Normal
UCUC
UCUC
The goals for the management of The goals for the management of acute ulcerative colitisacute ulcerative colitis
Induction of remissionInduction of remission Prevention of relapse Prevention of relapse Treatment of complicationsTreatment of complications
Therapeutic decisionsTherapeutic decisions
Disea
se
Activ
ity ?
?
Extent of
Disease ??
Disease ActivityDisease Activity
MildMild ModerateModerate SevereSevere FulminantFulminant
Mayo score
Schroeder KW et al. N Engl J Med 1987; 317: 1625-9.
Endoscopy Photo: Sample ScoresEndoscopy Photo: Sample Scores
Endoscopy score 1Endoscopy score 1Endoscopy score 0Endoscopy score 0
Endoscopy score 2Endoscopy score 2 Endoscopy score 3Endoscopy score 3
Severe colitisSevere colitis
A bloody stool frequency of > 6/day with any one of A bloody stool frequency of > 6/day with any one of the following:the following:
Tachycardia (pulse > 90 beats/min)Tachycardia (pulse > 90 beats/min) Temperature (> 37.8 °C)Temperature (> 37.8 °C) Anaemia (Hg < 10.5 g/dL)Anaemia (Hg < 10.5 g/dL) Raised ESR (> 30 mm/h) Raised ESR (> 30 mm/h)
Extent of Disease
Medical TherapyMedical Therapy
Activity Extent
Superiority of topical 5-ASA to placebo in treatment of mild to moderate Distal UC.
Seven RCTs
Superiority of topical 5-ASA to placebo in treatment of mild to moderate Distal UC.
5-aminosalicylic acid preparations (all study arms) compared with placebo in active ulcerative colitis.
Adapted from Sutherland et al. Ann Intern Med 1993; 118: 540–9.
Combined oral and topical treatment with 5-ASA in active extensive UC, proximal to the splenic flexure.
344344
64
0
10
20
30
40
50
60
70
80
90
100
4 weeks 8 weeks
% R
emis
sio
n
4.0g PO/D
4.0g po + 1.0genema/D
Marteau P et al. Gut 2005; 54: 960–5.
(NS)
P =0.03
Topical 5-ASA have superior efficacy to oral mesalazine in Topical 5-ASA have superior efficacy to oral mesalazine in the maintenance of remission in Distal Colitisthe maintenance of remission in Distal Colitis
68
32
8474
0102030405060708090
100
One year Two years
%
in r
emis
sio
n
Oral Mesalazine1.5g/D
Rectal Mesalazine4g twice/W
Mantzaris GJ et al. Dis Colon Rectum 1994; 37: 58–62.
RCTs of mesalazine vs. placebo for preventing relapse in patients with UC
27. Ardizzone S et al.Aliment Pharmacol Ther 1999; 13: 373–9.23. Hanauer S et al .Ann Intern Med 1996; 124: 204–11.25. Hawkey CJ et al. Gastroenterology 1997; 112: 718–24.24. Miner P et al. Dig Dis Sci 1995; 40: 296–304.
Compliance is a problemCompliance is a problem
Patient Non-compliance with 5-ASA Patient Non-compliance with 5-ASA Treatment RegimensTreatment Regimens
80
50
0
10
20
30
40
50
60
70
80
90
100
% c
om
pli
ance
to
tre
atm
ent
Clinical trials Community based studies
Kane SV et al. Am J Gastroenterol 2001; 96: 2929-33.
Clinical Impact of Non-adherence to therapy for UCClinical Impact of Non-adherence to therapy for UC
11
61
0
10
20
30
40
50
60
70
80
90
100
% o
f p
ati
en
ts r
ela
ps
es
Compliant Non-compliant
Kane S. Am J Med 2003; 114: 39-43.
Greater risk of symptomatic relapse
(P = 0.001)
Clinical Impact of Non-adherence to therapy for UCClinical Impact of Non-adherence to therapy for UC
3
31
0
10
20
30
40
50
60
70
80
90
100
% o
f C
olo
n c
an
ce
r
Compliance Non-compliance
10 years follow up
Greater risk of colorectal cancer
(P < 0.001)
175 patients The lifetime risk of colorectal cancer among patients with UC is estimated to be approximately 20%
Brentnall TA. Curr Opin Gastroenterol 2003; 19: 64-8.
Mesalazine 2 g Mesalazine 2 g gelgel enema is as effective as and more enema is as effective as and more
convenient than mesalazine 2 g convenient than mesalazine 2 g foam foam enemaenema
6
26 2625
50 48
0
10
20
30
40
50
60
70
Difficulty inretention
Abd Bloating Discomfort durigadminstration
Gel enema (50)
Foam enema (53)P<0.05
P<0.005 P<0.05
103 patients
4 weeks
Remission rates were comparable between the two groups.
Gionchetti P. Aliment Pharmacol Ther 1999; 13: 381-8.
SPD476* for the induction of remission in SPD476* for the induction of remission in
patients with mild-moderate UCpatients with mild-moderate UC
3429
12.9
55.759.6
25.9
0
10
20
30
40
50
60
70
1.2g BID 4.8g OD Placebo
Remission
Improvement
280 patients
8 weeks R×
A once-daily high-dose 5-ASA formulation using a novel multimatrix technology to delivers 1.2 g of drug per tablet to the entire colon
Lichtenstein GR et al, A Phase III study. Am J Gastroenterol. 2005;100:S-291. [Abstract #787]
SPD476* for the induction of remission in SPD476* for the induction of remission in patients with mild-moderate UCpatients with mild-moderate UC
40.5 41.2
32.6
60.764.7
55.8
0
10
20
30
40
50
60
70
80
2.4g OD 4.8g OD 800mg TID
Remission
Improvement
Kamm MA et al, Am J Gastroenterol. 2005;100:S-291. [Abstract #786]