management of perianal crohn ’s disease
Post on 13-Jan-2016
47 Views
Preview:
DESCRIPTION
TRANSCRIPT
Management of Perianal Crohn’s Disease
Yousif, A Qari MD, FRCPc, ABIMDepartment of Medicine
Division of Gaseroenteroloy King Abdulaziz University
Jeddah, Saudi Arabia
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.
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
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
Long-term evolution of Long-term evolution of Disease Disease
Behaviour in CDBehaviour in CD
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
Cu
mu
lativ
e in
cid
en
ce %
All fisulas
Perianal fistulas
Schwartz DA et a, Gastroenterology.2002;122;875 Cumulative incidence of perianal fistula is 23-38%.
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 o
f d
ev
elo
pin
g p
eri
an
al
fis
tula
e
Hellers G et at. Gut 1980; 21: 525–7.
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.
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
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.
Normal AnatomyNormal Anatomy
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
Classification proposed by AGA Classification proposed by AGA technical review on perianal Crohn's technical review on perianal Crohn's
diseasedisease
Simple 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.
Outcome Outcome measuresmeasures
Irvine EJ et al. McMaster IBD Study Group. J Clin Gastroenterol 1995; 20: 27–32.
Perianal Disease Activity Index
Outcome measuresOutcome measures MRI-based score
Van Assche G et al. Am J Gastroenterol 2003; 98(2): 332–9.
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.
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.
Therapeutic Therapeutic approachapproach
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
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
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
AntibioticsAntibiotics
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, alone
or in combination.¹or in combination.¹ ³³־־
Metronidazole20mg/kg/day
¹ Bernstein LH et al.Gastroenterology.1980;79;357
² Schneider MU et al. DIsch Med Wochenschr 1981;106;1126
³ Jakobvitz et al. Am J Gastroeterol.1984;79;533
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 A disulfiram-like response to alcohol
intake. 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.
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 al¹883- 12 3- 12
monthsmonths8 (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
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
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 ?
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
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)
Response47%
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
Ciprofloxacin 500mg BID combined Ciprofloxacin 500mg BID combined with Infliximab for Perianal Fistulas in with Infliximab for Perianal Fistulas in
CDCD
91
73
15
62 62
39
9
91
0
20
40
60
80
100
120
140
Week 6 Week 8 Week 12 Week 18
Time
Cli
nic
al
resp
on
se %
Cipro+Infliximab Placebo+Infliximab
P=1.0
P=0.17 P=0.17
P=0.12
Inflx Inflx Inflx
West RL et al, Aliment Pharmacol Ther 2004; 20: 1329–36.
24 Patients
MERCAPTOPURINEMERCAPTOPURINE AND AND
AZATHIOPRINEAZATHIOPRINE
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 Response
Response
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.
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]
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
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
Ciclosporin Ciclosporin and and
TacrolimusTacrolimus
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%
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. .
Side effects of Ciclosporin Side effects of Ciclosporin
include:include: HypertensionHypertension HeadacheHeadache HirsutismHirsutism HypertrichosisHypertrichosis HypertriglyceridaemHypertriglyceridaem
iaia NauseaNausea Gingival hyperplasiaGingival hyperplasia TremorTremor ParesthesiaParesthesia nephropathy nephropathy ImmunosuppressionImmunosuppression..
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
Fis
ula
im
pro
ve
me
nt
%
Tacrolimus 0.2mg/kg/d
Placebo
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
Tacrolimus (FK-506) in the Tacrolimus (FK-506) in the treatment of fistulizingtreatment of fistulizing Crohn’s Crohn’s
diseasedisease
Subanalysis 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.
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
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.
MethotrexateMethotrexate
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
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 p
atie
nts
A retrospective chart review of 16 patients with fistulizing crohn’s diseas 1989 - 1997
U. Mahadevan Aliment Pharmacol Ther 18(10):1003-1008, 2003 .
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
Infliximab (Anti-TNF-Infliximab (Anti-TNF-αα ) )
Infliximab for fistulizing Infliximab for fistulizing CDCD
Randomized, multicenter, double blind placebo controlled trial
26
62
0
20
40
60
80
100
% o
f p
atie
nts
ach
ievi
ng
p
rim
ary
end
po
int
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
Infliximab for fistulizing Infliximab for fistulizing CDCD
Randomized, multicenter, double blind placebo controlled trial
13
46
0
20
40
60
80
100
% o
f p
ati
en
ts a
ch
iev
ing
c
om
ple
te c
los
ure
of
fis
tua
e
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
Infliximab for fistulizing Infliximab for fistulizing CDCD
0
4
8
12
16
Infliximab5mg/kg
Infliximab10mg/kg
Total
Med
ian
du
rato
n o
f
fistu
la c
losu
re i
n w
eeks
)n=21( )n=18( )n=39(
Present DH et al. N Engl J Med. 1999;340;1398
Infliximab in maintaining closureInfliximab in maintaining closureof draining fistulaeof draining fistulae
Evaluation at week 54
All Patients, n = 306Infusion
Week 0 Infliximab 5 mg/kgWeek 2Week 6
Week 14 Responders n = 195 )69%(
Non-respondersn = 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.
Analysis at week Analysis at week 5454
Response
23
46
0
10
20
30
40
50
60
Placebo Infliximab
% w
ith
re
sp
os
e
Compleate response
19
36
0
10
20
30
40
50
60
Placebo Infliximab
% w
ith a
ll fis
tula
e c
lose
d
ACCENT II
195 patients
N Engl J Med 2004;350:876-85.
P=0.001P=0.001
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
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.
Infliximab both as an induction and maintenance agent; may not be the most cost-effective
treatment.
0102030405060708090
100
Co
mp
lete
fis
tula
clo
sure
%
75%
TNFAZT/6MP
A pilot study of 16 patients
Ochsenkuhn T et al. Am J Gastroenterol 2002; 97: 2022–5.
M10
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.
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 ) patients remained off infliximab and ciprofloxacininfliximab and ciprofloxacin. .
Schwartz DA. Inflamm Bowel Dis 2005; 11: 727–32.
OTHER MEDICAL TREATMENTSOTHER MEDICAL TREATMENTS
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.
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 before these treatments are consideredconsidered
Treatment Treatment AlgorithmAlgorithm
1. History & physical2. Endoscopy3. Imiging (MRI or EUS)
Simple fistula without rectalinflammation
Simple fistula with rectal
inflammationComplex fistula
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
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
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
top related