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Management of Perianal Crohn’s Disease Yousif, A Qari MD, FRCPc, ABIM Department of Medicine Division of Gaseroenteroloy King Abdulaziz University Jeddah, Saudi Arabia

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Management of Perianal Crohn ’s Disease. Yousif, A Qari MD, FRCPc, ABIM Department of Medicine Division of Gaseroenteroloy King Abdulaziz University Jeddah, Saudi Arabia. Perianal fistulas in CD. - PowerPoint PPT Presentation

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Page 1: Management of Perianal Crohn ’s Disease

Management of Perianal Crohn’s Disease

Yousif, A Qari MD, FRCPc, ABIMDepartment of Medicine

Division of Gaseroenteroloy King Abdulaziz University

Jeddah, Saudi Arabia

Page 2: Management of Perianal Crohn ’s Disease

Perianal fistulas in Perianal fistulas in CDCD

Perianal fistulas are a frequent Perianal fistulas are a frequent manifestation of Crohn's disease that can manifestation of Crohn's disease that can result in significant morbidity, including result in significant morbidity, including scarring, faecal incontinence, and even scarring, faecal incontinence, and even proctectomy in up to 10–18% of patients. proctectomy in up to 10–18% of patients.

Page 3: Management of Perianal Crohn ’s Disease

Long-Term Long-Term Treatment of Treatment of

Fistulizing Crohn’s Fistulizing Crohn’s DiseaseDisease

Epidemiology/ClassificationEpidemiology/Classification

Therapeutic goalsTherapeutic goals

Conventional therapiesConventional therapies

Anti-TNF- Anti-TNF- αα therapy therapy

Other therapiesOther therapies

Page 4: Management of Perianal Crohn ’s Disease

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

240228216204192180168156144132120108968472604836241200

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

Long-term evolution of Long-term evolution of Disease Disease

Behaviour in CDBehaviour in CD

Page 5: Management of Perianal Crohn ’s Disease

Cumulative incidence of Cumulative incidence of fistulafistula

0

10

20

30

40

50

60

1 year 5 years 10 years 20 years

Time from diagosis

Cum

ulat

ive

inci

denc

e %

All fisulasPerianal fistulas

Schwartz DA et a, Gastroenterology.2002;122;875 Cumulative incidence of perianal fistula is 23-38%.

Page 6: Management of Perianal Crohn ’s Disease

The risk of developing perianal The risk of developing perianal fistulas increases when the fistulas increases when the

disease involves the distal boweldisease involves the distal bowel

12

92

0

20

40

60

80

100

120

Ileal disease Rectal involvement

Ris

k of

dev

elop

ing

peria

nal f

istu

lae

Hellers G et at. Gut 1980; 21: 525–7.

Page 7: Management of Perianal Crohn ’s Disease

Distribution of Distribution of fistulaefistulae

Perianal 52%

Enteroenteric24%

Others15%

Retovaginal9%

From patients in the Olmstead County, Minnesota.Crohn's disease cohort, from 1970 to 1995

Schwartz DA et al. Gastroenterology 2002; 122: 875–80.

Page 8: Management of Perianal Crohn ’s Disease

The natural history of fistulizing The natural history of fistulizing Crohn's diseaseCrohn's disease

Crohn’s withPerianal fistulae

31%Medical treatment

69%Surgical treatment

69%Conservative

perianal surgery

31%Proctotectomy

Schwartz D. Gastroenterology 2000; 118(4): A337

population based study

Page 9: Management of Perianal Crohn ’s Disease

Accurately defining perianal Accurately defining perianal fistulae is a prerequisitefistulae is a prerequisite for for

medical and surgical treatment medical and surgical treatment strategiesstrategies

The course of the tracts through the anal sphincter The course of the tracts through the anal sphincter structuresstructures

NumberNumber

ComplexityComplexity

The presence of abscess.The presence of abscess.

the presence of stricturing intestinal disease the presence of stricturing intestinal disease

Schwartz DA,et al. Gastroenterology 2001; 121: 1064–72.

Page 10: Management of Perianal Crohn ’s Disease

Normal AnatomyNormal Anatomy

Page 11: Management of Perianal Crohn ’s Disease

Classification of Perianal Classification of Perianal FistulaFistula

A A Superficial fistulaSuperficial fistula B B Intersphincteric fistulaIntersphincteric fistula

CC Transsphincteric fistula Transsphincteric fistula

D D Suprasphincteric fistulaSuprasphincteric fistula

EE Extrasphincteric fistula Extrasphincteric fistula

Parks AG et al. Br J Surg 1976; 63(1): 1–12.

Park’s classification

Page 12: Management of Perianal Crohn ’s Disease

Classification proposed by AGA Classification proposed by AGA technical review on perianal Crohn's technical review on perianal Crohn's

diseasediseaseSimple fistulaSimple fistula

SuperficialSuperficial Inter-sphinctericInter-sphincteric low trans-sphinctericlow trans-sphincteric

One openingOne opening

NO abscessNO abscess

NO connection to an NO connection to an adjacent structure.adjacent structure.

Complex fistulaComplex fistula

Involves more of the Involves more of the anal sphincters anal sphincters High trans-sphincteric High trans-sphincteric

oror Extra-sphincteric orExtra-sphincteric or Supra-sphinctericSupra-sphincteric

Multiple openingsMultiple openings

Associated with:Associated with: perianal abscess perianal abscess Connects to an Connects to an

adjacent structure, adjacent structure, such as the vagina or such as the vagina or bladder. bladder.

AGA medical position statement: perianal Crohn's disease. Gastroenterology 2003; 125(5): 1503–7.

Page 13: Management of Perianal Crohn ’s Disease

Outcome Outcome measuresmeasures

Irvine EJ et al. McMaster IBD Study Group. J Clin Gastroenterol 1995; 20: 27–32.

Perianal Disease Activity Index

Page 14: Management of Perianal Crohn ’s Disease

Outcome measuresOutcome measures MRI-based score

Van Assche G et al. Am J Gastroenterol 2003; 98(2): 332–9.

Page 15: Management of Perianal Crohn ’s Disease

The optimal way to define a The optimal way to define a fistulafistula

Combination of two of the following Combination of two of the following tests:tests:

Magnetic resonance imaging (MRI) of the Magnetic resonance imaging (MRI) of the pelvispelvis

Endoscopic ultrasound (EUS)Endoscopic ultrasound (EUS)

Examination under anaesthesia Examination under anaesthesia Schwartz DA,et al. Gastroenterology 2001; 121: 1064–72.

Page 16: Management of Perianal Crohn ’s Disease

Spontaneous healing rate of Spontaneous healing rate of fistulae in patients with Crohn’s fistulae in patients with Crohn’s

diseasedisease TrialTrialActive Active

medicatiomedication n evaluatedevaluated

Number Number of of patientspatients

Time at Time at response response evaluateevaluatedd

Complete Complete closure of closure of fistulae (%)fistulae (%)

PresentPresent et al et al.¹.¹MPMP17171 year1 year1 (6)1 (6)

Present Present et alet al.².²InfliximabInfliximab313118 weeks18 weeks4 (13)4 (13)

Sandborn Sandborn et et alal.³.³

TacrolimusTacrolimus252510 weeks10 weeks2 (8)2 (8)

TotalTotal73737 (10)7 (10)

1. Present DH. N Engl J Med 1980; 302:981–7.

2. Present DH. N Engl J Med 1999; 340: 1398–405.

3. Sandborn WJ. Gastroenterology 2003;125: 380–8.

Page 17: Management of Perianal Crohn ’s Disease

Therapeutic Therapeutic approachapproach

Page 18: Management of Perianal Crohn ’s Disease

Therapeutic Goals in the Therapeutic Goals in the Management of Fistulizing Crohns Management of Fistulizing Crohns

DiseaseDisease Control overall disease activityControl overall disease activity

Induce closure of fistulasInduce closure of fistulas

Maintain closure of fistulasMaintain closure of fistulas

Limit scope of surgical interventionLimit scope of surgical intervention

Improve quality of lifeImprove quality of life

Page 19: Management of Perianal Crohn ’s Disease

Efficacy of agents evaluated to Efficacy of agents evaluated to treat fistulizing Crohn’s diseasetreat fistulizing Crohn’s disease

EffectivePossibly effectiveIneffectiveCiprofloxacinMetronidazoleMP/azathioprineTacrolimusInfliximab

CiclosporinGM-CSFHyperbaricoxygen

AminosalicylatesCorticosteroids

MP, mercaptopurine ;GM-CSF, granulocyte-macrophage colony-stimulating factor

Page 20: Management of Perianal Crohn ’s Disease

Onset of action of different Onset of action of different therapies on fistula closuretherapies on fistula closure

1 week 10 weeks 12 weeks 24 weeks

MP/Azathioprine

Infliximab

Cyclosporine & Tacrolimus

Antibiotics

2 weeks 4 weeks

Page 21: Management of Perianal Crohn ’s Disease

AntibioticsAntibiotics

Page 22: Management of Perianal Crohn ’s Disease

Antibiotics for Perianal Fistulas in Antibiotics for Perianal Fistulas in CDCD

Open trialsOpen trials

Complete healing reported in about 50%Complete healing reported in about 50%of patients receiving Metronidazole, aloneof patients receiving Metronidazole, aloneor in combination.¹or in combination.¹ ³³־־

Metronidazole20mg/kg/day

¹ Bernstein LH et al.Gastroenterology.1980;79;357² Schneider MU et al. DIsch Med Wochenschr 1981;106;1126³ Jakobvitz et al. Am J Gastroeterol.1984;79;533

Page 23: Management of Perianal Crohn ’s Disease

Antibiotics for Perianal Fistulas in Antibiotics for Perianal Fistulas in CDCD

Symptomatic recurrence in 78% of patients Symptomatic recurrence in 78% of patients within 4 months of stopping therapywithin 4 months of stopping therapy

Side effects of metronidazole include:Side effects of metronidazole include:

DyspepsiaDyspepsia Metallic taste Metallic taste A disulfiram-like response to alcohol intake. A disulfiram-like response to alcohol intake. Peripheral neuropathy and paresthesias Peripheral neuropathy and paresthesias

limit the use of this agent for long-term limit the use of this agent for long-term treatment.treatment.

Metronidazole

•Brandt LJ. Gastroenterology 1982; 83: 383–7.

Page 24: Management of Perianal Crohn ’s Disease

Antibiotics for Perianal fistulas in Antibiotics for Perianal fistulas in CDCD

TrialTrialNo. of No. of patientpatient

ss

Duration Duration of of

therapytherapy

ImprovemenImprovement of t of

symptomssymptoms(%)(%)

PersistencPersistence of e of

drainagedrainage

Closure Closure of of

fistulaefistulae

Turunen U Turunen U et al¹et al¹

883- 12 3- 12 monthsmonths

8 (100)8 (100)4400

Wolf J Wolf J et et al²al²

555 weeks5 weeks4 (80)4 (80)00

1 Turunen U et al. Scand J Gastroenterol 1989; 24 (Suppl. 48): 144.2 Wolf J et al. Gastroenterology 1990; 98: A212 (abstract).

Ciprofloxacin 500 - 1500mg/day

Page 25: Management of Perianal Crohn ’s Disease

Antibiotics for Perianal fistulas in Antibiotics for Perianal fistulas in CDCD

TrialTrialNo. of No. of patientspatients

Duration of Duration of therapytherapy

ImprovemenImprovement of t of

symptomssymptoms(%)(%)

Closure Closure of of

fistulaefistulae(%)(%)

Solomon et Solomon et alal

121212 weeks12 weeks9(75)9(75)3(25)3(25)

Solomon M et al, Can J Gastroenterol 1993; 7: 571–3.

Ciprofloxacin 1000 - 1500mg/day + Metronidazole 500-1500mg/day

Uncontrolled trial

Page 26: Management of Perianal Crohn ’s Disease

Antibiotics for Perianal fistulas in Antibiotics for Perianal fistulas in CDCD

Antibiotics are not the ideal solution to the Antibiotics are not the ideal solution to the problemproblem

Side effectsSide effects

Low rate of fistula closureLow rate of fistula closure

Recuurence on D/CRecuurence on D/C

Bridge strategy for azathioprine therapy ?Bridge strategy for azathioprine therapy ?

Page 27: Management of Perianal Crohn ’s Disease

Onset of action of different Onset of action of different therapies on fistula closuretherapies on fistula closure

1 week 10 weeks 12 weeks 24 weeks

MP/Azathioprine

Infliximab

Cyclosporine & Tacrolimus

Antibiotics

2 weeks 4 weeks

Page 28: Management of Perianal Crohn ’s Disease

Antibiotic and AZA for the Antibiotic and AZA for the treatment of perianal fistulas in treatment of perianal fistulas in

Crohn'sCrohn's disease.disease.

WithoutAZA

With AZA

After antibiotic Treatment Without antibiotics

Response41%

Response54%

No AZA

)n=19(

AZA

)n=14(

Response16%

Response50%

Continued

AZA (n=15)Response

47%

Week 8 Week 20

Relapse

Maintainedresponse

Maintainedresponse

Week 32

C. Dejaco et al Aliment Pharmacol Thera Volume 18 Issue 11-12 Page 1113 - 2003

(n=35)

(n=17)

Cipro+/-Flagyl

Page 29: Management of Perianal Crohn ’s Disease

Ciprofloxacin 500mg BID combined Ciprofloxacin 500mg BID combined with Infliximab for Perianal Fistulas in with Infliximab for Perianal Fistulas in

CDCD

9173

15

62 62

39

9

91

0

20

40

60

80

100

120

140

Week 6 Week 8 Week 12 Week 18

Time

Clin

ical

resp

onse

%

Cipro+Infliximab Placebo+Infliximab

P=1.0

P=0.17 P=0.17P=0.12

Inflx Inflx Inflx

West RL et al, Aliment Pharmacol Ther 2004; 20: 1329–36.

24 Patients

Page 30: Management of Perianal Crohn ’s Disease

MERCAPTOPURINEMERCAPTOPURINE AND AND

AZATHIOPRINEAZATHIOPRINE

Page 31: Management of Perianal Crohn ’s Disease

A meta-analysis incorporating five A meta-analysis incorporating five randomized,randomized,

placebo-controlled trials of MP or placebo-controlled trials of MP or azathioprineazathioprine

with fistula response as a secondary with fistula response as a secondary outcomeoutcome

21

54

79

46

0%10%20%30%40%50%60%70%80%90%

100%

Placebo AZT

No ResponseResponse

Pearson DC et al, A meta-analysis.Ann Intern Med 1995; 123: 132–42.

29 Patients

41 patients

Response : Either complete healing or decreased discharge from fistulae.

Page 32: Management of Perianal Crohn ’s Disease

Predicting clinical response to 6-MP/AZT using a combination of the 6-TGN metabolite level and TPMT activity

6-Thioguanine (6-TGN)A marker for drug efficacy

6-methylmercaptopurine (6-MMP)Associated with hepatotoxicity

6-MP/AZT

Allopurinol *

Thiopurine methyltransferase (TPMT)

5 ASA

Higher 6-MMP/6-TGN ratiosHigher relaps

Lower response

* Witte TN. Am J Gastroenterol. 2006;101:S432-433. [Abstract 1105]

Page 33: Management of Perianal Crohn ’s Disease

Improved efficacy of MP or azathioprine by tailoring of doses

using MP metabolites

Erethrocyte 6-thioguanine; 6-TGN) levelsErethrocyte 6-thioguanine; 6-TGN) levels(>250 pmol/8 ×10 red blood cells).(>250 pmol/8 ×10 red blood cells).

Could optimize clinical responseCould optimize clinical response

Cuffari C, et al. Gut 2001; 48: 642–6.

8

Page 34: Management of Perianal Crohn ’s Disease

Adverse events while on MP or Adverse events while on MP or azathioprineazathioprine

Pancreatitis (3%)Pancreatitis (3%) Allergic reactionsAllergic reactions InfectionsInfections LeucopoeniaLeucopoenia Drug-induced hepatitis Drug-induced hepatitis Small increase in risk of lymphomaSmall increase in risk of lymphoma

Page 35: Management of Perianal Crohn ’s Disease

Ciclosporin Ciclosporin and and

TacrolimusTacrolimus

Page 36: Management of Perianal Crohn ’s Disease

Ciclosporin may have a role in the Ciclosporin may have a role in the acute management of fistulizing acute management of fistulizing

Crohn’s disease.Crohn’s disease.

10 case series10 case series 64 patients64 patients

Initial response rate 83%Initial response rate 83% Sustained response 38%Sustained response 38%

Page 37: Management of Perianal Crohn ’s Disease

Ciclosporin may have a role in the Ciclosporin may have a role in the acute management of fistulizing acute management of fistulizing

Crohn’s disease.Crohn’s disease. Improvement typically within 1 weekImprovement typically within 1 week

Relapse rate is high on D/CRelapse rate is high on D/C ??Rescue therapy to induce fistula closure??Rescue therapy to induce fistula closure

??Bridge therapy to maintenance ??Bridge therapy to maintenance treatment with other slower acting treatment with other slower acting immune modifier agents, such as immune modifier agents, such as azathioprine or mercaptopurineazathioprine or mercaptopurine. .

Page 38: Management of Perianal Crohn ’s Disease

Side effects of Ciclosporin Side effects of Ciclosporin include:include:

HypertensionHypertension HeadacheHeadache HirsutismHirsutism HypertrichosisHypertrichosis HypertriglyceridaemiHypertriglyceridaemi

aa NauseaNausea Gingival hyperplasiaGingival hyperplasia TremorTremor ParesthesiaParesthesia nephropathy nephropathy ImmunosuppressionImmunosuppression..

Page 39: Management of Perianal Crohn ’s Disease

Tacrolimus (FK-506) in the treatment Tacrolimus (FK-506) in the treatment of fistulizing Crohn’s diseaseof fistulizing Crohn’s disease

43

8

0102030405060708090

100

Tacrolimus0.2mg/kg/d

Placebo

Fisu

la im

prov

emen

t %

Tacrolimus 0.2mg/kg/dPlacebo

Randomized double-blind placebo-controlled multicentre trial 43

patientsP= 0.004

Fistula improvement defined as: closure of ‡50% of fistulae that were draining at baseline and maintenance of closure for ‡4 weeks)

Sandborn WJ et al, Gastroenterology 2003; 125: 380–8.

Therapy for 10 weeks

Abdominal fistulae failed to close

Page 40: Management of Perianal Crohn ’s Disease

Tacrolimus (FK-506) in the Tacrolimus (FK-506) in the treatment of fistulizingtreatment of fistulizing Crohn’s Crohn’s

diseasediseaseSubanalysis of the same study:Subanalysis of the same study:

15 patients treated with infliximab in the 15 patients treated with infliximab in the pastpast

47% improved on tacrolimus.47% improved on tacrolimus. ?? alternative therapy in patients ?? alternative therapy in patients

Intolerant to infliximab Intolerant to infliximab Refractory to infliximabRefractory to infliximab

Sandborn WJ et al, Gastroenterology 2003; 125: 380–8.

Page 41: Management of Perianal Crohn ’s Disease

Tacrolimus should likely remain Tacrolimus should likely remain an agent of last resort.an agent of last resort.

Known side effects of Tacrolimus:Known side effects of Tacrolimus:

HeadacheHeadache InsomniaInsomnia ParesthesiaParesthesia Tremor Tremor Increased serum creatinineIncreased serum creatinine

Page 42: Management of Perianal Crohn ’s Disease

The Perianal Disease Activity Index

The PDAI score is a simple 5-point index Scores range from 0 to 20 Higher scores indicate more severe disease activity. The five elements are

The presence or absence of discharge Pain or restriction of daily living activities Restriction of sexual activity The type of perianal disease The degree of induration

Irvine EJ et al. McMaster IBD Study Group. J Clin Gastroenterol 1995; 20: 27–32.

Page 43: Management of Perianal Crohn ’s Disease

MethotrexateMethotrexate

Page 44: Management of Perianal Crohn ’s Disease

MethotrexatMethotrexatee

Has been shown to induce and maintain Has been shown to induce and maintain remission in patients with Crohn’s diseaseremission in patients with Crohn’s disease

But its role in treating Crohn’s disease But its role in treating Crohn’s disease fistulae has not been adequately studied. fistulae has not been adequately studied.

TrialNo. of patients

Duration of treatment

Partial fistula closure(%)

Comlete fistula closure (%)

Soon SY et alMethotrexate for fistulizing CD

186 months44%22%

Soon SY. Eur J GastroenterolHepatol 2004; 16: 21–6.

A retrospective review of a single centre’s experience

Page 45: Management of Perianal Crohn ’s Disease

Fistula Response to Fistula Response to Methotrexate in Crohn's Methotrexate in Crohn's Disease: A Case SeriesDisease: A Case Series

3125

0102030405060708090

100

Response Closure

Mean treatment duration 15.5 months

% o

f pat

ient

s

A retrospective chart review of 16 patients with fistulizing crohn’s diseas 1989 - 1997

U. Mahadevan Aliment Pharmacol Ther 18(10):1003-1008, 2003 .

Page 46: Management of Perianal Crohn ’s Disease

Adverse events of Adverse events of MethotrexateMethotrexate

Intestinal distress and alopecia are dose related and indicators of Intestinal distress and alopecia are dose related and indicators of unacceptable toxicityunacceptable toxicity

Idiosyncratic allergic-type reactions Idiosyncratic allergic-type reactions Rash Rash Pneumonitis in 3-11%Pneumonitis in 3-11%

Liver toxicityLiver toxicity Abnormal serum ALT (30%)Abnormal serum ALT (30%) Histological abnormalitiesHistological abnormalities

95% mild95% mild 2% hepatic fibrosis.2% hepatic fibrosis.

Contraindications: Contraindications: Other risk factors for liver diseaseOther risk factors for liver disease Men and women attempting conceptionMen and women attempting conception

Page 47: Management of Perianal Crohn ’s Disease

Infliximab (Anti-TNF-Infliximab (Anti-TNF-αα ) )

Page 48: Management of Perianal Crohn ’s Disease

Infliximab for fistulizing Infliximab for fistulizing CDCD

Randomized, multicenter, double blind placebo controlled trial

26

62

0

20

40

60

80

100

% o

f pat

ient

s ac

hiev

ing

prim

ary

end

poin

t

Placebo Infliximab

W0 W2 W6 W10 W14 W18

Treatment period

Primary end point : at least 50% reduction from baseline of the number of draining fistulae on at least two consecutive assessments )performed at times of infusion

and at 10, 14 and 18 weeks( .Present DH. N Engl J Med 1999; 340: 1398–405.

94 patients

P=0.002

Response

Page 49: Management of Perianal Crohn ’s Disease

Infliximab for fistulizing Infliximab for fistulizing CDCD

Randomized, multicenter, double blind placebo controlled trial

13

46

0

20

40

60

80

100

% o

f pat

ient

s ac

hiev

ing

com

plet

e cl

osur

e of

fist

uae

Placebo Infliximab

W0 W2 W6 W10 W14 W18

Treatment period

A complete response )defined as the absence of any draining fistulae at two consecutive visits(

Present DH. N Engl J Med 1999; 340: 1398–405.

94 patients

P=o.oo1

Complete closure

Page 50: Management of Perianal Crohn ’s Disease

Infliximab for fistulizing Infliximab for fistulizing CDCD

0

4

8

12

16

Infliximab5mg/kg

Infliximab10mg/kg

Total

Med

ian

dura

ton

of

fistu

la c

losu

re in

wee

ks

)n=21( )n=18( )n=39(

Present DH et al. N Engl J Med. 1999;340;1398

Page 51: Management of Perianal Crohn ’s Disease

Infliximab in maintaining closureInfliximab in maintaining closureof draining fistulaeof draining fistulae

Evaluation at week 54

All Patients, n = 306InfusionWeek 0 Infliximab 5 mg/kg

Week 2Week 6Week 14 Responders

n = 195 )69%(Non-responders

n = 87 )31%(

Week 22

Placebomaintenance

n = 99

Infliximab 5 mg/kg

maintenancen = 96

Infliximab5 mg/kg

q 8 weeks

Infliximab10 mg/kgq 8 weeks

Week 30

Week 38

Week 46

24 patients discontinued

ACCENT II

N Engl J Med 2004;350:876-85.

Page 52: Management of Perianal Crohn ’s Disease

Analysis at week Analysis at week 5454

Response

23

46

0

10

20

30

40

50

60

Placebo Infliximab

% w

ith re

spos

e

Compleate response

19

36

0

10

20

30

40

50

60

Placebo Infliximab

% w

ith a

ll fis

tula

e cl

osed

ACCENT II

195 patients

N Engl J Med 2004;350:876-85.

P=0.001P=0.001

Page 53: Management of Perianal Crohn ’s Disease

Major issues, to consider Major issues, to consider when starting infliximabwhen starting infliximab

Abscess formationAbscess formation:: Rapid closure of the cutaneous opening of the Rapid closure of the cutaneous opening of the

fistula fistula Reported incidence is 5 -15%¹Reported incidence is 5 -15%¹ ֿֿ³³ Risk is reduced by placement of a non-cutting Risk is reduced by placement of a non-cutting

seton before initiating infliximabseton before initiating infliximab

Infections

1 Ricart E. et al. Am J Gastroenterol 2001;96,3:722-729.2 Present DH,. N Engl J Med 1999; 340: 1398–405

3 Sands BEClin Gastroenterol Hepatol 2004;2: 912–204 Wise PE. Clin Gastroenterol Hepatol 2006; 4: 426–30.

4

Page 54: Management of Perianal Crohn ’s Disease

Draining seton helps to maintain Draining seton helps to maintain fistula drainage until the tract fistula drainage until the tract

becomes inactivebecomes inactive Single center experience: Complete response in 67%

Topstad DR et al. Dis Colon Rectum 2003; 46(5): 577–83.

Page 55: Management of Perianal Crohn ’s Disease

Infliximab both as an induction and maintenance agent; may not be the most cost-effective

treatment.

0102030405060708090

100

Com

plet

e fis

tula

clo

sure

%

75%

TNF AZT/6MP

A pilot study of 16 patients

Ochsenkuhn T et al. Am J Gastroenterol 2002; 97: 2022–5.

M10

Page 56: Management of Perianal Crohn ’s Disease

Advantages to concomitant AZA/6-MP Advantages to concomitant AZA/6-MP for patients on infliximabfor patients on infliximab

Decreased rate of adverse reactions related to Decreased rate of adverse reactions related to antibody formation to infliximabantibody formation to infliximab

Preservation of drug efficacyPreservation of drug efficacy Increased and more prolonged response rates.Increased and more prolonged response rates.

1. Ochsenkuhn T et al. Am J Gastroenterol 2002; 97(8): 2022–5.

2. Baert F. et al. N Engl J Med 2003; 348(7): 601–8.

Page 57: Management of Perianal Crohn ’s Disease

Infliximab may not be required for Infliximab may not be required for maintenance therapy if fistulae heal maintenance therapy if fistulae heal

completely

21 patients21 patients were treated with infliximab, were treated with infliximab, ciprofloxacin and MP for medical management of ciprofloxacin and MP for medical management of fistulizing CD fistulizing CD

In 18/21 patients (In 18/21 patients (86%86%), the fistulae stopped ), the fistulae stopped draining.draining.

11of these 18 patients (11of these 18 patients (52%52%) had fistula closure ) had fistula closure documented by EUSdocumented by EUS

7 of these 11(7 of these 11(33%33%) patients remained off infliximab ) patients remained off infliximab and ciprofloxacinand ciprofloxacin. .

Schwartz DA. Inflamm Bowel Dis 2005; 11: 727–32.

Page 58: Management of Perianal Crohn ’s Disease

OTHER MEDICAL TREATMENTSOTHER MEDICAL TREATMENTS

Page 59: Management of Perianal Crohn ’s Disease

Granulocyte-macrophage Granulocyte-macrophage colony-stimulating factor (GM-colony-stimulating factor (GM-

CSF)CSF)

Treatment group

No. of patients

Duration of treatment

Decreased drainage

(%)

No drainage(%)

Placebo556 days02(40%)GM-CSF856 days1(12.5%)4(50%)

A randomized, placebo-controlled trial

Korzenik JR. N Engl J Med 2005; 352: 2193–201.

Page 60: Management of Perianal Crohn ’s Disease

Other Other therapiestherapies

Mycophenolate mofetilMycophenolate mofetil Thalidomide Thalidomide OctreotideOctreotide HyperbaricHyperbaric oxygenoxygen Further studies need to be performed Further studies need to be performed

before these treatments are consideredbefore these treatments are considered

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Treatment Treatment AlgorithmAlgorithm

1. History & physical2. Endoscopy3. Imiging (MRI or EUS)

Simple fistula without rectalinflammation

Simple fistula with rectal

inflammationComplex fistula

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Treatment AlgorithmTreatment Algorithm(Simple fistula without rectal (Simple fistula without rectal

inflammation)inflammation)Simple fistula without rectalinflammation

Antibiotics and AZA/6-MP

Consider Infliximab

Treatment failure Treatment success

Treat as a complex Fistulizing process

Continue AZA/MP -/+Infliximab

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Treatment AlgorithmTreatment Algorithm (Simple fistula with rectal (Simple fistula with rectal

inflammation)inflammation)Simple fistula

with rectalinflammation

Antibiotics, AZA/6-MP

& Infliximab

Treatment failure Treatment success

Treat as a complex Fistulizing process

Continue AZA/MP -/+Infliximab

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Treatment AlgorithmTreatment Algorithm (Complex fistula)(Complex fistula)

Complex fistula

1. Surgical evaluation2. Antibiotics, AZA/6-MP & Infliximab

Treatment failure Treatment success

Consider TacrolimusIn selected patients

Continue AZA/MP -/+Infliximab

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