Treatment Algorithms in Crohn’s DiseaseTreatment Algorithms in Crohn’s Disease

Gary R. Lichtenstein, M.D.Gary R. Lichtenstein, M.D.Professor of MedicineProfessor of Medicine

University of Pennsylvania School of MedicineUniversity of Pennsylvania School of MedicineHospital of the University of PAHospital of the University of PA

PhiladelphiaPhiladelphiaPennsylvaniaPennsylvania

Premise and PreviewPremise and Preview

In Most Clinical Scenarios ofIn Most Clinical Scenarios ofCrohn’s DiseaseCrohn’s Disease

Therapy is SequentialTherapy is Sequential

Goals of Therapy for IBDGoals of Therapy for IBD

• Inducing remissionInducing remission

• Maintaining remissionMaintaining remission

• Restoring and maintaining nutritionRestoring and maintaining nutrition

• Maintaining patient’s quality of lifeMaintaining patient’s quality of life

• Surgical intervention (selection of optimal Surgical intervention (selection of optimal time for surgery)time for surgery)

Crohn’s Disease:Crohn’s Disease:Anatomic DistributionAnatomic Distribution

Small bowelSmall bowelalonealone(33%)(33%)

Colon aloneColon alone(20%)(20%)

IleocolicIleocolic(45%)(45%)

LeastLeastMostMost

Freq of involvementFreq of involvement

Long-term Evolution of Long-term Evolution of Disease Behavior in CDDisease Behavior in CD

Cosnes J et al. Inflamm Bowel Dis. 2002;8:244.

24022821620419218016815614413212010896847260483624120

0

10

20

30

40

50

60

70

80

90

100

Cum

ulat

ive

Pro

babi

lity

(%)

Patients at risk:Months

2002 552 229 95 37N =

Penetrating

StricturingInflammatory

0.0

0.2

0.4

0.6

0.8

1.0

0 20 40 60

Proportion of CD Patients in Each Proportion of CD Patients in Each Treatment State by Year Treatment State by Year

Since CD DiagnosisSince CD Diagnosis

Silverstein MD et al. Gastroenterology 1999;117:49

Years after Diagnosis

Pro

bab

ilit

y

Post-surgeryremissionSurgeryDrug refractoryDrug dependentDrug responsiveMildRemission

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

Cumulative Incidence of Surgical Resection Over 1 Year in CD Cumulative Incidence of Surgical Resection Over 1 Year in CD Patients Starting CorticosteroidsPatients Starting Corticosteroids

Days

Cu

mu

lativ

e P

rob

ab

ility

(%

)

0

20

40

60

80

100

0 30 60 90 182 365

Faubion WA Jr et al. Gastroenterology. 2001;121:255.N = 77.

Inductive TherapiesInductive Therapiesfor Crohn’s Diseasefor Crohn’s Disease

• AminosalicylatesAminosalicylates

• AntibioticsAntibiotics

• CorticosteroidsCorticosteroids

• InfliximabInfliximab

Therapeutic PyramidTherapeutic Pyramidfor Active Crohn’s Diseasefor Active Crohn’s Disease

SevereSevere

ModerateModerate

Aminosalicylates/AntibioticsAminosalicylates/Antibiotics

CorticosteroidsCorticosteroids

ImmunomodulatorsImmunomodulators

SurgerySurgery

InfliximabInfliximab

??(Prednisone)(Prednisone)

MildMild

(Budesonide)(Budesonide)

Treatment of Mild-ModerateTreatment of Mild-ModerateCrohn’s DiseaseCrohn’s Disease

NCCDS: Response to Therapy for NCCDS: Response to Therapy for Active Crohn’s DiseaseActive Crohn’s Disease

NCCDS, National Cooperative Crohn’s Disease Study.Summers RW et al. Gastroenterology 1979;77:847-869

PatientsPatients(%)(%)

Weeks after RandomizationWeeks after Randomization00 55 1010 1515

Sulfasalazine 1 g/15 kg (5 g)Sulfasalazine 1 g/15 kg (5 g)

PlaceboPlacebo

6060

5050

4040

3030

2020

1010

00

7070

13%13%

Meta-Analysis of PentasaMeta-Analysis of Pentasa®® (4g/day) (4g/day) in Active Crohn’s Diseasein Active Crohn’s Disease

P=0.005P=0.005

P=0.7P=0.7 P=0.5P=0.5

P=0.04P=0.04

Hanauer, Stromber. Clinical Gastroenterology & Hepatology 2004

P=0.005P=0.005

P=0.7P=0.7

P=0.05P=0.05P=0.04P=0.04

-80

-70

-60

-50

-40

-30

-20

-10

0

Crohn's I

n=155

Crohn’s II

n=150

Crohn's III

n=310

Overall

n=615

Ch

an

ge

fro

m b

as

eli

ne

in

CD

AI

sc

ore

Pentasa® 4 g Placebo

-60

-50

-40

-30

-20

-10

0

Crohn's I

n=155

Crohn's II

n=150

Crohn's III

n=310

Overall

n=615

Pentasa® 4 g minus Placebo

Antibiotics in Active CDAntibiotics in Active CD

0

10

20

30

40

50

60

70

Metro + CiproMetro + Cipro MetroMetro CiproCiprovs. Me-Predvs. Me-Pred vs. SASPvs. SASP vs. Mesalaminevs. Mesalamine

% R

emis

sio

n

Prantera 1996; Ursing 1982; Colombel 1999

Corticosteroids in Crohn’s DiseaseCorticosteroids in Crohn’s Disease

Faubion et al (Olmsted County, 1970-93)Faubion et al (Olmsted County, 1970-93)

““Only 43% of inception cohort everOnly 43% of inception cohort everrequired steroids”required steroids”

Corticosteroids in CD:Corticosteroids in CD:Induction of RemissionInduction of Remission

*Randomized controlled trial†Multicenter prospective trial

Malchow H et al. Gastroenterology. 1984;86:249.Modigliani R et al. Gastroenterology. 1990;98:811.

Summers RW et al. Gastroenterology. 1979;77:847.

Clinical Remission

% P

atie

nts

30%

82%*

38%

p not calculated92%

†

60%*

17 weeks 18 weeks 7 weeksNCCDS ECCDS GETAID

0

20

40

60

80

100 Corticosteroids

Placebo

Corticosteroid Therapy for Corticosteroid Therapy for Crohn’s DiseaseCrohn’s Disease

*30 days after initiating corticosteroid therapy

Complete Remission

58%(n = 43)

PartialRemission

26%(n = 19)

Immediate Outcome*(n = 74)

1-YearOutcome(n = 74)

Steroid Dependent

28%(n = 21)

Prolonged Response

32%(n = 24)

Surgery 38%

(n = 28)

NoResponse

16%(n = 12)

Faubion W et al. Gastroenterology 2001;121:225

Outcome of Corticosteroid Outcome of Corticosteroid Therapy for CDTherapy for CD

Remission48%

Improved 32%

No change20%

12-monthoutcomes

1-monthoutcomes

Remission54%

Relapse46%

Improved57%

Relapse43%

Munkholm. Gut 1994;35:360-362

* Remission at 12 Months = 25%

23%

75%

30%

76%

0

10

20

30

40

50

60

70

80

Smith Summers Malchow

Steroid

Placebon=59; p=NS

Corticosteroids: Corticosteroids: Maintenance of RemissionMaintenance of Remission

% P

atie

nts

in

Rem

issi

on

n=274; p=NS

n=237; p=NS

36 months 12 months 24 months

Smith RC et al. Gut. 1978;19:606.Summers RW et al. Gastroenterology. 1979;77:847.

Bergman L et al. Scand J Gastroenterol. 1976;11:651.Malchow H et al. Gastroenterology. 1984;86:249.

55%58%

Overview of Corticosteroids in CDOverview of Corticosteroids in CD

• Induce remission (NCCDS,Induce remission (NCCDS,** ECCDS, ECCDS,†† GETAIDGETAID‡‡))

• Provide rapid symptomatic relief (NCCDS,Provide rapid symptomatic relief (NCCDS,** ECCDS,ECCDS,†† GETAID GETAID‡‡))

• Frequent corticosteroid dependency with Frequent corticosteroid dependency with prolonged useprolonged use

• DO NOT maintain remissionDO NOT maintain remission• Dose- and duration-related adverse events Dose- and duration-related adverse events

with acute and chronic therapywith acute and chronic therapy

Faubion WA Jr et al. Gastroenterology. 2001;121:255.Keenan GF et al. Clin Chest Med. 1997;18:507.

Munkholm P et al. Gut. 1994;35:360.Singleton JW et al. Gastroenterology. 1979;77:870.

Steinhart AH et al. Cochrane Database Syst Rev. 2003;CD000301.

*Summers RW et al. Gastroenterology. 1979;77:847.†Malchow H et al. Gastroenterology. 1984;86:249.‡Modigliani R et al. Gastroenterology. 1990;98:811.

Remission Rates in Acute Crohn’s StudiesRemission Rates in Acute Crohn’s Studieswith Budesonide CIRwith Budesonide CIR

Bud CIRBud CIR Bud CIRBud CIR PlaceboPlacebo Pentasa Pentasa®® Prednisolone Prednisolone 9 mg QD9 mg QD 4.5 mg BID4.5 mg BID 2 g BID2 g BID 40 mg 40 mg

Remission rates atRemission rates at8 weeks (%)8 weeks (%)

Greenberg 1994; Rutgeerts 1994; Thomsen 1998

0

10

20

30

40

50

60

70

Maintenance TherapyMaintenance Therapyfor Crohn’s Disease: Issuesfor Crohn’s Disease: Issues

• Definition of remissionDefinition of remission– Clinical, endoscopic, radiologic, laboratoryClinical, endoscopic, radiologic, laboratory

• Induction therapyInduction therapy– 5-ASA, steroids, antibiotics, immunomodulators5-ASA, steroids, antibiotics, immunomodulators– SurgerySurgery

• Disease location Disease location • Disease behaviorDisease behavior

– Inflammatory, fibrostenotic, fistulizingInflammatory, fibrostenotic, fistulizing

• SmokingSmoking

Months after RandomizationMonths after Randomization

Summers. Gastroenterology 1979

NCCDS - Response to Therapy for NCCDS - Response to Therapy for Crohn’s Disease Remission MaintenanceCrohn’s Disease Remission Maintenance

Mesalamine Maintenance ofMesalamine Maintenance ofRemission in Crohn’s DiseaseRemission in Crohn’s Disease

Camma. Gastro 1997Favors TreatmentFavors Treatment

StudyStudy YearYear Pts (n)Pts (n)CaprilliCaprilli 19941994 9595McLeodMcLeod 19951995 163163BrignolaBrignola 19951995 8787SutherlandSutherland 19971997 6666OverallOverall 411411

ThornsonThornson 19901990 248248PranteraPrantera 19921992 125125BrignolaBrignola 19921992 4444GendreGendre 19931993 161161BresciBresci 19941994 6666ThornsonThornson 19951995 286286ArberArber 19951995 5959ModiglianiModigliani 19961996 8585SutherlandSutherland 19971997 180180De FranchisDe Franchis 19971997 117117OverallOverall 1,3711,371

-0.5-0.5 -0.4-0.4 -0.3-0.3 -0.2-0.2 -0.1-0.1 0.00.0 0.10.1 0.20.2 0.30.3 0.40.4 0.50.5Favors ControlFavors Control

Risk Difference 95% CIRisk Difference 95% CI

Oral Budesonide as Maintenance Oral Budesonide as Maintenance Therapy for CDTherapy for CD

Adapted from Greenberg GR et al. Gastroenterology 1996;110:45-51

PP == nsns

Budesonide 6 mgBudesonide 6 mg

Budesonide 3 mgBudesonide 3 mg

PlaceboPlacebo

DaysDays00 100100 200200 300300

Cu

mu

lati

ve p

rob

abili

ty

Cu

mu

lati

ve p

rob

abili

ty

of

rem

issi

on

of

rem

issi

on

00

0.50.5

11

Outcomes for Mild-Moderate DiseaseOutcomes for Mild-Moderate Disease

Mild-Moderate Disease

AminosalicylateResponse 40-50%

Antibiotic(Colonic Disease)Response 40-50%

Budesonide(Ileum-Right Colon)Response 50-65%

PlaceboResponse 30-40%

““Evidence-Based” Approach of Evidence-Based” Approach of Sandborn and FeaganSandborn and Feagan

Mild-Moderate Mild-Moderate Crohn’s DiseaseCrohn’s Disease

Left-sided disease restricted to colon Disease involving the ileumLeft-sided disease restricted to colon Disease involving the ileum and/or ascending colonand/or ascending colon

SulfasalazineSulfasalazine16 weeks16 weeks

Budesonide capsulesBudesonide capsules8-16 weeks8-16 weeks

Sulfa-allergic/failed treatment Failed treatmentSulfa-allergic/failed treatment Failed treatment

Conventional steroidsConventional steroids

>60%>60% 45% acute45% acute80% 1 year80% 1 year

Sandborn, Feagan, 2003

Evidence/Experience Evidence/Experience Aminosalicylate InductionAminosalicylate Induction

Mesalamine/Sulfasalazine

Response No Response

Maintain Ileum-R. Colon Colon Moderate Disease

Budesonide AntibioticPrednisone/

Elemental DietInfliximab

Prescriptions are Written on Paper…Prescriptions are Written on Paper…Not in StoneNot in Stone

Until we can predict course in Until we can predict course in individual patients…individual patients…

Advance to more potent, more toxic Advance to more potent, more toxic agents if no initial response or relapse agents if no initial response or relapse

TopicsTopics

• Antimetabolite therapyAntimetabolite therapy

• Anti-inflammatory cytokinesAnti-inflammatory cytokines

• TNF blockade TNF blockade

0

20

40

60

80

% R

esp

on

se

0 10

Weeks

Prednisone Placebo AZA

P=0.17

NCCDS DataNCCDS Data

AZA: Induction of RemissionAZA: Induction of Remission

AZA and 6-MP: Induction of AZA and 6-MP: Induction of Remission in CDRemission in CD

Pearson DC et al. Ann Intern Med 1995;122:132-142.

Azathioprine for Crohn’s DiseaseAzathioprine for Crohn’s Disease

0 0

20 20

40 40

60 60

80 80

100 100

00 11 22 33 44 55 66 77 88 99 1010 1111 1212 1313 1414 1515

Duration of Trial (months)Duration of Trial (months)

AZAAZA PlaceboPlacebo

Per

cen

t o

n T

rial

Per

cen

t o

n T

rial

Candy S et al. Gut 1995

Combination Induction TherapyCombination Induction Therapy6-MP + Prednisone6-MP + Prednisone

• Pediatric CDPediatric CD

• Patients who required Patients who required steroid therapysteroid therapy

• 6-MP 1.5 mg/kg added 6-MP 1.5 mg/kg added as primary therapyas primary therapy

• Improved outcomesImproved outcomes

Markowitz J. Gastroenterology 2000;119:895-902

Days Since Steroids DiscontinuedDays Since Steroids Discontinued

00 100100 200200 300300 400400 500500 60060000

.25.25

.50.50

.75.75

1.001.00

Fra

ctio

n S

tero

id F

ree

Fra

ctio

n S

tero

id F

ree

Azathioprine and 6-Mercaptopurine Azathioprine and 6-Mercaptopurine in IBD: Toxicityin IBD: Toxicity

• CommonCommon– Gastrointestinal Gastrointestinal

intoleranceintolerance– MyalgiaMyalgia

• UncommonUncommon– Bone marrow Bone marrow

suppressionsuppression– PancreatitisPancreatitis– Allergic reactions Allergic reactions – Hepatic toxicityHepatic toxicity

Present DH. Gastroenterol Clin North Am 1989;18:57-71

– Opportunistic Opportunistic infection infection

– Neoplasm Neoplasm

MethotrexateMethotrexate

Historical OverviewHistorical Overview

• 1948 1948 –– first “designer drug” first “designer drug” specific antagonist of folic acidspecific antagonist of folic acid

• 1950’s 1950’s –– serendipitous discovery serendipitous discoveryof activity in psoriasisof activity in psoriasis

• 1960’s 1960’s –– widely used for widely used for psoriasis psoriasis –– hepatotoxic hepatotoxic

• 1966 1966 –– Enderlin reported use in Enderlin reported use in RARA

• 1985 1985 –– Wienblatt defines Wienblatt defines pharmacokinetics in RApharmacokinetics in RA

• 1980-2000 1980-2000 –– treatment of choice treatment of choicefor RAfor RA

Feagan. N Eng J Med. 1995;332(5):292-7

% R

esp

on

se

% R

esp

on

se

0 0

25 25

19.1%19.1% 39.4%39.4%

P P =0.025=0.025

PlaceboPlacebo MTXMTX

5050

MTX Results: RemissionMTX Results: Remission

Methotrexate: Time to RelapseMethotrexate: Time to Relapse%

Re m

issi

on

% R

e mis

sio

n

Weeks Since RandomizationWeeks Since Randomization

P P =0.044=0.044

MethotrexateMethotrexate

PlaceboPlacebo

Feagan BG. N Engl J Med 2000;342(22):1627-32

Methotrexate in IBD: ToxicityMethotrexate in IBD: Toxicity

• MajorMajor– HepaticHepatic– MyelosuppressiveMyelosuppressive– PulmonaryPulmonary– Fertility-relatedFertility-related– TeratogenicTeratogenic– Enteritic/coliticEnteritic/colitic

Egan LJ, Sandborn WJ. Mayo Clin Proc 1996;71:69-80

• MinorMinor– GastrointestinalGastrointestinal– Alopecia-inductiveAlopecia-inductive– AllergicAllergic– NeurologicNeurologic

CyclosporineCyclosporine

Cyclosporine in CDCyclosporine in CD

Feagan BG. Inflammatory Bowel Dis 1995;1:335-339

Biologic TherapyBiologic Therapy

Infliximab: Mechanism of ActionInfliximab: Mechanism of Action

Healing of Colonic UlcerationHealing of Colonic Ulcerationwith Infliximabwith Infliximab

Van Dullemen HM et al. Gastroenterology 1995;109:129-135

PretreatmentPretreatment 4 weeks 4 weeks post-treatmentpost-treatment

Median Time to Loss of ResponseMedian Time to Loss of ResponseThrough Week 54Through Week 54

Week 2 RespondersWeek 2 Responders

ACCENT I

Hanauer S, Feagan B. Lancet. 2002;359:1541-9

Clinical Remission at Week 54*Clinical Remission at Week 54*

*Week-2 responders

0

10

20

30

40

50

Single Dose(n=110)

Pro

po

rtio

n o

f P

atie

nts

(%

)

5 mg/kgq 8 wk(n=113)

10 mg/kgq 8 wk(n=112)

P<0.001

P=0.007 P=NS

14%

28%

38%

ACCENT IACCENT I

Hanauer SB, et al. Lancet 2002

REMICADEREMICADE®® (infliximab) in Patients (infliximab) in Patients with Fistulizing Crohn’s Diseasewith Fistulizing Crohn’s Disease

Complete Response: All Fistulas ClosedComplete Response: All Fistulas Closed

P=0.001

P=0.04

*Placebo=Conventional Therapy*

Present, et al.

Present D, et al. N Engl J Med. 1999;340:1398-1405.

Fistula Response at Week 54Fistula Response at Week 54

23%27%

49%

40%

0

20

40

60

80

100

Fistula Response Complete Response

Placebo maintenance 5 mg/kg infliximab maintenance

P=0.014

Pat

ien

ts i

n R

esp

on

se (

%)

P=0.002

Sands BE, et al NEJM 2004

ACCENT IIACCENT II

Among Patients Responding at Weeks 10 and 14Among Patients Responding at Weeks 10 and 14

41/8324/89 41/8324/89

Fistula Response at Week 54Fistula Response at Week 54

23%27%

49%

40%

0

20

40

60

80

100

Fistula Response Complete Response

Placebo maintenance 5 mg/kg infliximab maintenance

P=0.014

Pat

ien

ts i

n R

esp

on

se (

%)

P=0.002

Sands, B et al. NEJM 2004

ACCENT IIACCENT II

Among Patients Responding at Weeks 10 and 14Among Patients Responding at Weeks 10 and 14

41/8324/89 41/8324/89

Incidence of Antibodies-to-Infliximab (ATI) Incidence of Antibodies-to-Infliximab (ATI) Maintenance Studies*Maintenance Studies*

Maintenance StudiesMaintenance Studies

% of Pts without ATI% of Pts without ATI% of Pts with ATI% of Pts with ATI % of Patients Inconclusive% of Patients Inconclusive††

* pts with evaluable samples* pts with evaluable samples

ACCENT I ACCENT I CDCD

n = 514n = 514Week 72Week 72

16

2758

ACCENT IIACCENT IICDCD

n = 258n = 258Week 54Week 54

17

52

31

ATTRACTATTRACTRARA

n = 295n = 295Week 102Week 102

9

56

36

Antibody-to-Infliximab (ATI) StatusAntibody-to-Infliximab (ATI) Status

†† pts with long-lasting serum concentrations of infliximab and never ATI (+)pts with long-lasting serum concentrations of infliximab and never ATI (+)

11

49

40

ASPIREASPIRERARA

n = 629n = 629Week 54Week 54

ASPIRE: Integrated Safety Summary, Sep. 18, 2003

Infliximab and Antibody FormationInfliximab and Antibody Formation

• Cohort study (n = 125): mean of 3.9 infusions / Cohort study (n = 125): mean of 3.9 infusions / 10 months10 months

• 61% of patients developed ATI61% of patients developed ATI

• Antibody formation inversely associated with serum Antibody formation inversely associated with serum infliximab concentrationinfliximab concentration

• ATI formation > 8 ug predicted shorter duration of ATI formation > 8 ug predicted shorter duration of response (35 vs. 71 days) – present in 37%response (35 vs. 71 days) – present in 37%

• Approximately 2.5 times as likely to form ATI if Approximately 2.5 times as likely to form ATI if concomitant antimetabolite therapy was not usedconcomitant antimetabolite therapy was not used

Baert et al. N Engl J Med 2003;348:7

Prevention of ATIs Prevention of ATIs

• Avoid intermittent therapyAvoid intermittent therapy

• Use effective preventative strategies:Use effective preventative strategies:– 200 mg solucortef IV ADC at time of 200 mg solucortef IV ADC at time of

dosing if not on a therapeutic dose of dosing if not on a therapeutic dose of antimetabolite*antimetabolite*

– MTX/AZA for chronic useMTX/AZA for chronic use

* Farrell R. Gastroenterology 2003;124(4):917-24

CD: Mild to ModerateCD: Mild to ModerateActive symptoms/

flare

Budesonide

Observe Taper

Consider budesonidetitrated to symptoms

or6-MP/AZA

orMTX

Not confined to

Prednisone

Taper

6-MP/AZAor

MTX

Consider 5-ASAConsider Abx

ObserveNo flare No flare

Flare

Response

No response

Exclude entericpathogen

Flare

Response

Ileal/ R colonileal/ R colon

CD: Moderate to SevereCD: Moderate to SevereModerate CD

Observe TaperSuccess

PO Steroids

6-MP/AZA

Consider change to MTX

Add infliximab

Surgery or investigational

therapy

Severe CD

IV Steroids

Adequate response

Inadequate response

• Consider infliximab+ 6-MP/AZA or MTX

• Consider surgery

Adequate response

Failure

Maintain6-MP/AZA or MTX

Maintaininfliximab +

6-MP/AZA or MTX

Adequate response

Adequate response

Adequate response

Inadequate response

Inadequate response/intolerant

Inadequate response/intolerant

Inadequate response/intolerant

InfliximabInfliximabInfliximab indicated

• Exclude enteric pathogen

• Exclude abscess, stricture

• Exclude latent/active TB

Infliximab 5 mg/kg wks 0, 2, 6

• Consider steroid pre-treatment

• Consider acetaminophen, diphenhydramine pre-treatment

Infliximab 10 mg/kg

Surgery or investigational Rx

Observe up to 8 wks

Recurrent sx≤ 4 wks

Recurrent sx> 4 - < 8 wks

Recurrent sx≥ 8 wks

Response

Maintain infliximab5 mg/kg q 4-8 wks

Inadequate response

Escalate dose or shorten interval Maintain infliximab5 mg/kg q 8 wks

Loss of response

Inadequate response

Inadequate response

(Start 6-MP/AZA or MTX)

FistulaFistulaFistula

Diagnosticevaluation

Fistula type

Not superficial

Superficial

• Antibiotics• Consider

fistulotomy

Observe

FailureFailure

FailureDefinitivesurgery Maintain

6-MP/AZAand/or infliximab

Failure

Tacrolimus• Seton

• Antibiotics

• 6-MP/AZA ± infliximab

Final PointsFinal Points• There is no “one size fits all” to IBD therapyThere is no “one size fits all” to IBD therapy

– Therapy and decision making are tailored to the Therapy and decision making are tailored to the individualindividual

• Algorithms are based upon available evidenceAlgorithms are based upon available evidence– Evidence is in constant fluxEvidence is in constant flux

• Success of algorithms depends upon optimization Success of algorithms depends upon optimization of each step of therapy and considerable judgment of each step of therapy and considerable judgment about each outcomeabout each outcome– Skillful application of medical therapy makes all the Skillful application of medical therapy makes all the

difference in outcomesdifference in outcomes