5/13/2017 InflammatoryBowelDiseaseTreatment&Management:ApproachConsiderations,SymptomaticTherapy/SupportiveCare,OverviewofStepwiseTherapy

InflammatoryBowelDiseaseTreatment&
Management
Updated:Jun17,2016
Author:WilliamARowe,MDChiefEditor:BSAnand,MDmore...

TREATMENT

ApproachConsiderations
The2goalsoftherapyaretheachievementofremission(induction)andthepreventionofdisease
flares(maintenance).Notethatatopdownapproach,withearlierintroductionofbiologicsand
immunomodulators,isfrequentlyadvocatedtoforestallcomplications.[76]

Thecareofapatientwithinflammatoryboweldisease(IBD)canbeeithermedicalorsurgicalin
natureor,inmanypatients,acombinationofboth.Themanagementalgorithmisalsodependenton
whetherthediagnosisisCrohndiseaseorulcerativecolitis.Themedicalapproachforpatientswith
IBDisbothsymptomaticcare(ie,reliefofsymptoms)andmucosalhealingfollowingastepwise
approachtomedication,withescalationofthemedicalregimenuntilaresponseisachieved.

Theconceptofdeepmucosalhealing,particularlyinCrohndisease,isbecomingincreasingly
advocated.Thereareseveralstudies,primarilyinvolvingantiTNFagents(andoccasionallyimmune
modifiers)thathaveshownthattheeliminationofinflammation(asdemonstratedbyendoscopicand
histologiccriteria)resultsinadecreaseintherateofsurgery,theuseofcorticosteroids,andtherate
ofhospitalization.[77,78,79,80,81,82,83]Thissupportstheuseofimmunemodifyingagents
(mercaptopurineorazathioprine)oroneoftheantiTNFagentsearlierinthecourseofIBD.[77,78,79,
80,81,82,83]

SymptomaticTherapy/SupportiveCare
Symptomatictherapy
Inadditiontotreatmentoftheunderlyinginflammation,patientswithinflammatoryboweldisease(IBD)
mayrequiresymptomatictherapy,particularlywhentheirsymptomsarenotrelatedtoactive
inflammation.Treatmentwithantidiarrhealagentssuchasloperamineordiphenoxylate/atropine
shouldgenerallybeavoidedinpatientswithactiveinflammation,asthesedrugscanprecipitatetoxic
megacoloninindividualswithsignificantcolonicinflammation.Similarly,otheragentsthatmayhave
anticholinergiceffectsshouldbeavoided,althoughantispasmodicmedicationsmaysometimesbe
usefulforsymptomaticrelief.InpatientswithCrohndiseasewhohavesignificantilealdiseaseorwho
havehadanilealresection,diarrheamaysometimesbeduetobilesaltmalabsorption.Insuch
patients,treatmentwithbilebindingresins,suchascholestyramine,maybehelpfulinmanagingthe
diarrhea.

Supportivecare

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IBDflaresinpatientswithmildtomoderatediseaseareusuallymanagedinanoutpatientsetting.
However,animportantandsometimesoverlookedconcerninthemanagementofIBDisthedosing
anddurationoftheuseofcorticosteroidtherapy.Foraflareofmoderateseverity,adoseof
prednisoneof2040mg/dayorequivalentisoftensufficienttotreattheflares.Oncesymptomsare
controlled,adedicatedtaperingprogressionofthesteroidfollows.

Patientsarecandidatesforimmunomodulators(azathioprine,6mercaptopurine,methotrexate)or
antiTNFagents(infliximab,adalimumab,certolizumabpegol)andbiologicagentsifflaresare
frequent(>12times),ifthedurationofsteroiduseisprolonged(morethanafewweeksperyear),if
reductionofthesteroiddosecausesrecurrenceofsymptoms(steroiddependent),orifsteroidsdonot
appeartobeworking(steroidrefractory).

AhealthmaintenanceissueofparticularimportancetopatientswithIBDisareductioninbonedensity
becauseofdecreasedcalciumabsorption(duetotheunderlyingdiseaseprocess)orcorticosteroid
use.Osteoporosisisaveryseriouscomplication,involving40%ofpatientswithIBD,andincreases
theriskforfractures.Allpatientswhohavebeenusingsteroidsforlongerthan3months,aswellas
postmenopausalwomen,shouldundergotestingwithbonedensitystudiestreatmentwith
bisphosphonatesandcalciumsupplementscanbeinitiatedinpatientswithsignificantlylowbone
density.

OverviewofStepwiseTherapy
Astepwiseapproach(nowgenerallyreferredtoasthestepupapproach),suchasoutlinedinthe
followingsections,maybetakeninmildtomoderateinflammatoryboweldisease(IBD).

ThefirststepinmedicationtherapyforIBDisusuallyaminosalicylates.Thereareseveraldifferent
aminosalicylates,butnonehavebeenconsistentlydemonstratedtobesuperiortotheothersforall
patients.Theseagentsappeartohavegreaterefficacyforthetreatmentofulcerativecolitisthanfor
Crohndisease,forwhichefficacydataarelimited.ForCrohndisease,metronidazoleorciprofloxacin
isoccasionallyused,particularlyforperianaldiseaseoraninflammatorymass.

Ifthepatient'sconditionfailstorespondtoanadequatedoseofaminosalicylates,thesecondstepis
oftencorticosteroids,whichtendtoproviderapidreliefofsymptomsandasignificantdecreasein
inflammation.[84]ThemostcommonrangeformoderateflaresofIBDisoralprednisoneat1040
mg/dayformoresevereflares,thehigherendoftherangeisused(occasionallydosesupto60
mg/day).Onceaclinicalresponseisseen,thedoseistapered.Mostpatientswhouseoral
corticosteroidscantoleratearelativelyrapidtaperafteraresponseisachievedoccasionally,avery
prolongedsteroidtaperisnecessarytopreventrelapseinpatientswhohavehadprolongedexposure
tosteroidsinthepast.Inabilitytotaperdownthesteroidswithoutrecurrenceofsymptomsshould
triggerdiscussionregardingtheuseofalternativedrugs(immunomodulatorsorantiTNFtherapy).

TheimmunemodifyingagentsarestepIIIdrugsandareusedifcorticosteroidsfailorarerequiredfor
prolongedperiods.AntiTNFmonoclonalantibodytherapiesarealsostepIIIdrugsthatareeffectivein
bothCrohndiseaseandulcerativecolitissomestudieshavedemonstratedthattheyhaveagreater
efficacythanazathioprine.Traditionally,antiTNFagentshavebeenadministeredwhenChron
diseasehasbeenunresponsivetosteroidsandimmunosuppressantshowever,theearlyintroduction
oftheseagentsinconjunctionwithimmunosuppressantsinthosewithanincreasedriskofa
complicated,severe,orpossiblyaggressiveIBDhasthepotentialtomodifythediseasecourse.[76]

Drugsfromdifferenttherapeuticclassesmaybeusedadditively.Insomepatientswithhighrisk
disease,astepdownapproachwithearlyintroductionofstrongeragentssuchastheantiTNFagents
hasbeenadvocatedtopreventcomplicationsandimprovepatientoutcomes.Therearemany

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situations,especiallyinpatientswithmoreseveredisease,wherethestepdownapproachisclearlyin
thepatientsbestinterest.

Ingeneral,onemajorgoalistoweanthepatientoffsteroidsassoonaspossibletopreventlongterm
adverseeffectsfromtheseagents.Ardizzoneetalsuggestthatalackofmucosalhealingafter
corticosteroidtherapyistheonlyfactorassociatedwithnegativeoutcomesat5years.[85]

StepIAminosalicylates
The5oralaminosalicylatepreparationsavailableforuseintheUnitedStatesaresulfasalazine
(Azulfidine),mesalamine(Asacol,AsacolHD,Pentasa,Lialda,Apriso),balsalazide(Colazal),and
olsalazine(Dipentum).Enemaandsuppositoryformulationsarealsoavailable.Alloftheseare
derivativesof5aminosalicylicacid(5ASA)themajordifferencesareinthemechanismandsiteof
delivery.Someoftheseagentsalsohaveuniqueadverseeffectslackinginotheragentsofthisclass.

AlloftheaminosalicylatesareusefulfortreatingflaresofIBDandformaintainingremission.Noneof
theaminosalicylateshasbeenproventohavegreaterefficacythananyoftheothersforthetreatment
ofulcerativecolitis.Asaclass,theseagentsappeartobemoreeffectiveinpersonswithulcerative
colitisthaninpersonswithCrohndiseaseinpersonswithmildCrohndisease,theprimaryutilityisfor
colonicdisease(asisthecasewithsulfasalazine[1]administerfolicacidifsulfasalazineisused).
AminosalicylateshaveonlyaweakeffectinpreventingrecurrenceaftersurgeryinpatientswithCrohn
disease.[86]

Forpatientsinremissionfromdistalulcerativecolitis,oralorrectal5ASAcanbeusedtomanagethis
disease,aswellasacombinationregimenoforalandtopical5ASA.[1]Intreatingrectaldisease,
rectal5ASAispreferredoverrectalsteroids.[1]Adoseresponsehasbeendescribedregardingthe
useoftheseagentsforulcerativecolitis.Formoderatedisease,adoseof4.8g/dayofmesalamine
hasbeenshowntobemoreefficaciousthan2.4g/day.[87]

Probioticagents

Supplementationofthehighpotencyprobioticmixtures(eg,VSL#3[25,88,89])havebeenshownin
somereportstoreduceulcerativecolitisdiseaseactivityindexscoresinpatientswithmildtomoderate
relapsingulcerativecolitiswhoarebeingtreatedwith5ASA.StudiesinpatientswithCrohndisease
havebeenmuchlesspromising.

StepIAAntibiotics
Theantibioticsmetronidazoleandciprofloxacinarethemostcommonlyusedantibioticsinpersons
withinflammatoryboweldisease(IBD).Accordingtoasystemicreview,antituberculosistherapy,
macrolides,fluoroquinolones,5nitroimidazoles,andrifaximin(aloneorincombination)havenot
consistentlybeenshowntoinduceremissioninselectiveactiveCrohndiseaseandhaverarelybeen
showntoinduceremissioninulcerativecolitis.[90]

Antibioticsareusedonlysparinglyinpersonswithulcerativecolitisbecauseoflimitedtreatment
efficacyandbecauseofanincreasedriskofdevelopingantibioticassociatedpseudomembranous
colitis.InpersonswithCrohndisease,antibioticsareusedforvariousindications,mostcommonlyfor
perianaldisease,fistulas,andintraabdominalinflammatorymasses.

Antibioticshavepotentialadverseeffects,includingnausea,anorexia,diarrhea,andmonilial
(candidal)infections.Peripheralneuropathycanbeobservedinassociationwithmetronidazoleand,
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whenpresent,requiresdiscontinuationoftherapywiththatdrug.Finally,antibioticscanalsoincrease
theriskofClostridiumdifficilecolitis.

StepIICorticosteroids
Corticosteroidsarerapidactingantiinflammatoryagentsusedinthetreatmentofinflammatorybowel
disease(IBD).Thesedrugsareindicatedforacuteflaresofdiseaseonlyandhavenoroleinthe
maintenanceofremission.

Corticosteroidsmaybeadministeredbyvariousroutesdependingonthelocationandseverityof
diseasetheymaybeadministeredintravenously(ie,methylprednisolone,hydrocortisone),orally(ie,
prednisone,prednisolone,budesonide,dexamethasone),ortopically(ie,enema,suppository,orfoam
preparations).Corticosteroidsarelimitedbytheiradverseeffects,particularlywithprolongeduse.

Thepotentialcomplicationsofcorticosteroiduseincludefluidandelectrolyteabnormalities,
osteoporosis,avascularbonenecrosis,pepticulcers,cataracts,glaucoma,neurologicandendocrine
dysfunctions,infectiouscomplications,andoccasionalpsychiatricdisorders(includingpsychosis).

Theconsensusregardingtreatmentwiththeseagentsisthattheyshouldbetaperedonceremission
hasbeeninduced.(seeSurgicalIntervention,below,forinformationonTaperingcorticosteroidsinthe
postoperativesetting).Corticosteroidsdonothavearoleinmaintainingremission.

Patientswhoareconcernedaboutimmunosuppressivetherapies,includingimmunomodulatorsor
antitumornecrosisfactor(TNF)agents,shouldbeeducatedaboutthepotentialgreaterincidenceof
complicationsoccurringwithlongtermsteroiduseandwithundertreateddisease.Patientswith
prolongeduseofsteroidsmayalsorequireophthalmologicexaminationbecauseoftheriskof
developmentofglaucomaandcataracts.

Periodicassessmentofbonemineraldensityisrecommendedforpatientstakingsteroidsformore
than3months.[91]Agentsusedforosteoporosispreventionandtreatment(eg,thebisphosphonates)
areusefulforpreventingthebonelossassociatedwithcorticosteroiduse.

Intravenouscorticosteroids
Intravenouscorticosteroidsareoftenusedinpatientswhoareseverelyillandhospitalizedfewdata
havebeenpublishedontheoptimumdosageofIVororalcorticosteroids.Theupperendofdosing
generallyincludesIVmethylprednisoloneat20mgevery6hoursorIVhydrocortisoneat100mg
every8hours.Typically,onceaclinicalresponseisobserved(usuallywithin35days),thedoseofthe
IVcorticosteroidcanbetapered.Beforehospitaldischarge,conversiontoanoralcorticosteroidis
madewithdosagetaperinginanoutpatientsetting.

Oralcorticosteroids

Whenoralcorticosteroidsareused,dosingisvariable,andfewdatahavebeenpublishedtoguide
optimaldosing.ThemostcommonrangeformoderateflaresofIBDisprednisoneat1040mg/day.
Formoresevereflares,dosesupto60mg/daymaybeused,buttherearenosupportivedata.Once
aclinicalresponseisseen,thedoseistapered.Mostpatientswhouseoralcorticosteroidscan
occasionallytoleratearelativelyrapidtaperafteraresponseisachievedaprolongedsteroidtaperis
rarelynecessarytopreventrelapse.Whenthelattersituationoccurs,considerescalationoftherapy
withtheuseofalternativedrugs(immunemodifiersorantiTNFtherapy).

Budesonide(EntocortEC),asyntheticcorticosteroid,isavailableforCrohndiseasewithilealor
ileocecalinvolvement.[71]Budesonidehasextensivefirstpassmetabolism,whichlimitssystemic
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adverseeffects.[91]However,someabsorptionoccursoveraprolongedperiodofexposure.
Budesonideisalsolesseffectivethanotherstandardglucocorticosteroidsforthetreatmentofileal
Crohndiseaseandhasnotdemonstratedefficacyinmaintainingtherapybeyond12months.[90]

AccordingtotheAmericanGastroenterologicalAssociation(AGA)guidelines,ilealrelease
preparationsofbudesonideareindicatedforthetreatmentofpatientswithmildtomoderateilealand
rightsidedcolonicCrohndisease.[91]Thesepreparationshavenotbeendemonstratedtobeeffective
inpatientswithulcerativecolitis,butclinicaltrialsinthissettingareunderway.[91]

Topicalcorticosteroids
Topicalcorticosteroidsareusedinpersonswithdistalcolonicdiseaseinamannersimilartothatof
topicalmesalaminethemajordifferenceisthateventhoughtopicalmesalaminemaybeusedtohelp
maintainremission,topicalcorticosteroidsareusedforactivediseaseandhaveonlyasmallrolein
themaintenanceofremission.AccordingtoAGAguidelines,topicaltherapywitheitherhydrocortisone
(gradeArecommendation)orbudesonide(gradeBrecommendation)iseffectivefordistalcolonic
inflammationinpatientswithmildtomoderateIBD.[91]

Patientswithulcerativecolitiswithpredominantlydistaldiseasemaybetreatedwithtopical
budesonide,asyntheticsteroidwhichhaslocalantiinflammatoryeffectsandlimitedsystemiceffects.
[92] Althoughtopicalbudesonideiseffective,noveloralcontrolledreleaseformulationshavebeen

developedtoenabletreatmentoftheentirecolon.[92]

Rectalcorticosteroids

Cortenema,Cortifoam,andAnusolHCsuppositoriesareusefulintreatingdistaldisease(proctitisand
proctosigmoiditis).

StepIIIImmunomodulators
Immunemodifiershaveasloweronsetofaction(typically,a2to3monthlag)and,consequently,are
notusedforinductionofremission.However,theseagentshaveshowneffectivenessfortheirsteroid
sparingactioninpersonswithrefractorydiseasetheyarealsousedasprimarytreatmentforfistulas
andmaintenanceofremissioninpatientsintolerantofornotresponsivetoaminosalicylates.

Theimmunomodulators6mercaptopurine(6MP)andazathioprine(AZA)areusedinpatientswith
inflammatoryboweldisease(IBD)inwhomremissionisdifficulttomaintainwiththeaminosalicylates
alone.CalcineurininhibitorssuchascyclosporinA(CSA)andtacrolimus,aswellasmethotrexate
(MTX),arealsoimmunemodifyingagents[1]CSAisalmostexclusivelylimitedtoacutesevere
colitis,whereastacrolimushasbeenusedinbothperianalCrohndiseaseandulcerativecolitis.[1]

DataonMTXsupporttheuseofintramuscularMTXinCrohndisease,butsuchdataarelackingin
ulcerativecolitis.TheonlytrialofMTXinulcerativecolitisusedalowdoseoraltherapy[93]whethera
higherdoseoralMTXorparenteralMTX(IMorSQ)maybeeffectiveinulcerativecolitishasnotbeen
studied.SeveralclinicaltrialsshowedthatAZAcontinuationinpatientswithulcerativecolitis
preventedrelapse,ascomparedtothosewhodiscontinuedthemedication.However,othertrialshave
showntrendsbutnostatisticallysignificantbenefitofAZAinulcerativecolitis.[94]

Thiopurineagents

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TheAmericanGastroenterologicalAssociation(AGA),inaccordancewiththeUSFoodandDrug
Administration(FDA),recommendsthatpatientsundergoassessmentofthethiopurine
methyltransferase(TPMT)genotypeorphenotypebeforestartingtherapywithAZAor6MP.[91]
IndividualswhohavelowenzymeactivityorarehomozygousdeficientintheTPMTmutationareat
riskofverysevereleukopenia,withpotentialsepticcomplications,andmaynotbegoodcandidates
fortherapywiththesedrugs.[91]

About11%ofindividualswithheterozygousTPMTactivityrespondwelltotherapybutareproneto
myelotoxicity,althoughthiscanbeminimizedwiththeuseoflowerdoses.Thesepatients,aswellas
thosewithwildtypeTPMTactivity,requiremonitoringforcomplications.[91]

Adverseeffectsandmonitoring

Useofimmunemodifiersmandatesmonitoringofbloodparameterstheycancausesignificant
neutropeniaorpancytopeniathatwarrantsadosereductionordiscontinuation.Routinecomplete
bloodcell(CBC)countswithdifferentialsandplateletcountsarecheckedmonthly,andliverfunction
tests(LFTs)canbeperformedintermittently.Afterayearofstabledosingwithnodifficultieswithblood
counts(excepttheexpectedlymphopenia),theintervalbetweenbloodcountmonitoringcanbe
increased.

Thecytopeniceffectistypicallydosedependent,althoughsomepatientsaremoresensitivethan
others.ThetypicalAZAdoseis22.5mg/kg/day,whereasthedoseof6MPis11.5mg/kg/day.In
somestudies,bloodlevelsof6thioguaninehasbeenshowntoguidedosing,butsuchtestsofferlittle
advantage,atamuchgreatercostforroutinemonitoringanddoseadjustment,overCBCcountsand
liverfunctiontests.Inindependentstudies,metabolitelevelshavenotshownanycorrelationwith
clinicalefficacy,buttheymayhelpinmonitoringcompliance.

Otheradverseeffectsoftheimmunemodifiersincludefever,rash,infectiouscomplications,hepatitis,
pancreatitis,andbonemarrowdepression.Themostcommonreasonfordiscontinuingtheimmune
modifierswithinthefirstfewweeksisthedevelopmentofabdominalpainoccasionally,a
biochemicallydemonstrablepancreatitisoccurs.

Concernshavebeenraisedaboutthedevelopmentofmalignancyinpatientstaking6MPand
azathioprine.Theseagentshavebeenassociatedwitha2to4foldgreaterincidenceoflymphoma
andanincreaseinnonmelanomaskincancers,butcuriously,thereisa3.5folddecreaseincolorectal
carcinoma.

AntiTNFalphamonoclonalantibodies
Infliximab

Infliximab(Remicade)isanantiTNFalphamonoclonalantibodythatisadministeredbyinfusionfor
thetreatmentofCrohndisease.InfliximabisFDAapprovedforbothulcerativecolitisandCrohn
diseaseitappearstohaveahigherefficacyrateinCrohndisease.Infliximabisgenerally
administeredas3separateinfusionsof5mg/kgfortheinductionofremissionofmoderatetosevere
IBDatweeks0,2,and6,followedbyinfusionsevery8weeksformaintenanceofremission.Vande
Casteeleetalfoundthattargetingthetroughconcentrationsofinfliximabtolevelsof37g/mL
resultsinamoreefficientuseofthisagentinpatientswIthIBD.[95]

AsystemicreviewoftheefficacyofbiologictherapiesinIBDconfirmedthatantiTNFalphaagents
andnatalizumabwereeffectiveininducingremissionofactiveCrohndisease.[96]ForCrohndisease,
theresponseratemaybeashighas80%(theusualresponseratetonatalizumabisabout60%),and

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theinductionofremissionrateis3050%afterasingledosewithmultipledosing,higherratesof
remissionareattained.Forulcerativecolitis,theresponseratesmaybeashighas5070%.

PatientswithmoderatetosevereCrohndiseasewhohavedocumentedactiveinflammation,
dependenceoncorticosteroidsandaninabilitytotapertheseagents,ordiseaserefractorytosteroids
aremostlikelytobenefitfromantiTNFtherapy.[97]BeforeantiTNFagentsareadministered,
screeningshouldbedoneforcoexistentinfectionwithperianalandabdominalabscess(including
Mycobacteriumtuberculosis),andcautionisadvisedifapatientisacarrierforthehepatitisBvirus.
[97]

Cessationofinfliximabtherapy,eveninpatientswhoareinprolongedremission,isassociatedwith
highratesofdiseaseflare.Inastudyof115patientswithCrohndiseasewhoweretreatedfora
minimumof1yearwithinfliximabandanantimetabolite,whohadatleast6monthsofcorticosteroid
freeremission,andwhosubsequentlystoppedinfliximabtherapy,45%(52/115)hadarelapseata
medianof28monthsfollowup,witha1yearrelapserateof43.9%.[98]Riskfactorsforrelapse
includedmalesex,leukocytecountgreaterthan6.0109/L,Creactiveproteinlevelof5.0mg/Lor
greater,andafecalcalprotectinlevelof300g/gormore.Retreatmentwithinfliximabwas
successfulin88%ofpatientswhohadarelapse.[98]

InfliximabisalsoindicatedforthetreatmentoffistulizingCrohndisease.Forthisindication,thefistula
responds(closes)in68%ofpatientstreatedwithinfliximab,although12%maydevelopanabscess.
Theresponsecanbemaintainedbycontinuingregulardosing(ie,every8weeks)aftertheinduction
dose.

Adverseeffectsofinfliximab

Theadverseeffectsofinfliximabareuncommonbutcanincludehypersensitivityandflulike
symptomsthelattercanoftenbeavoidedbypretreatmentwithacetaminophenand
diphenhydramine.Therehavebeenrarereportsoflupuslikereactionsandlymphoproliferative
malignancies,althoughwhetherthemalignanciesarerelatedtothedrugortotheunderlyingdisease
processremainsuncertaintheyaremorelikelyduetotheconcomitantuseofimmunomodulators.

Adalimumab,certolizumab,golimumab

OtherantiTNFagentsincludeadalimumab(Humira),whichisgivenbysubcutaneous(SC)injection
every2weeksafteraloadingdoseof6injectionsover4weeks[99]certolizumabpegol(Cimzia),
whichisgivenbySCinjectionevery4weeksandgolimumab(Simponi),whichisgivenby
subcutaneous(SC)injectionevery4weeksaftertwoloadingdoses.

Natalizumab

Natalizumab(Tysabri),anagentaimedatpreventingtheaccumulationoflymphocytesinthediseased
bowelbyblockingtheeffectsofboth47integrin(gutspecific)and41integrin(CNSspecific),has
beenapprovedbytheFDA,butitisonlyavailablethrougharestricteddistributionprogram.
NatalizumabisanintravenousmedicationthathasshownefficacyinCrohndisease,buttherehave
been3reportsofprogressivemultifocalleukoencephalopathy,apotentiallyfatalopportunisticviral
infection.Riskistypicallyapparentinthosewithpriorimmunosuppressantexposureorwithaduration
ofinfusionforlongerthan2years.[100]

Vedolizumab

Vedolizumab(Entyvio),anotherintegrinantagonist,isapprovedforCrohndiseaseandulcerative
colitis.[101]Itisspecificfor47integrin.Approvalwasbasedonseveralphase3clinicaltrialsthat
simultaneouslyevaluatedvedolizumabforbothulcerativecolitisandCrohndiseaseandinvolved
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patientsinnearly40countries.AmongpatientswithCrohndiseasewhohadaresponsetoinduction
therapywithvedolizumab,39.0%ofthoseassignedtovedolizumabevery8weekswereinclinical
remissionatweek52,comparedwith21.6%assignedtoplacebo.

Inpatientswithulcerativecolitiswhohadaresponsetovedolizumabinduction,41.8%continuedtobe
inclinicalremissionat52weekscomparedwith15.9%ofpatienttakingplacebo.

StepIVClinicalTrialAgents
Clinicaltrialagentstendtobediseasespecific(ie,anagentworksforCrohndiseasebutnotfor
ulcerativecolitis,orviceversa).Theseincludeantiadhesionmoleculesandanticytokinetherapies.[1]
InCrohndisease,additionalagentsincludeTcellmarkertherapiesandmesenchymalstemcellsin
ulcerativecolitis,antiinflammatoryproteinshavealsobeenstudied.[1]

ExperimentalagentsusedinpersonswithCrohndiseaseincludethalidomide(50300mg/dayPO)
andinterleukin(IL)11(1mg/wkSC).Experimentalagentsusedinpersonswithulcerativecolitis
includenicotinepatch(1421mg/dayviatopicalpatch),butyrateenema(100mLperrectumtwice
daily),andheparin(10,000USCtwicedaily).Multiplecontraindications,interactions,andprecautions
areassociatedwiththesedrugs.

InpatientManagement
Patientsshouldbeadmittedtothehospitalifsurgicalinterventionisanticipatedoriftheircondition
doesnotrespondtooutpatienttreatment,iftheyaredehydrated,oriftheyhaveuncontrolledpainor
diarrhea.StartIVhydration.Ifindicated,obtainanabdominalflatplateimagetoexcludeobstruction
ormegacolon.Ifthepatientisnauseousorvomitingorhasevidenceofobstructionormegacolon,
nasogastricintubationmaybehelpful.Considerearlyconsultationwithasurgeoninthesettingof
severecolitisorbowelobstruction.

Ifthepatienthasactivecolitis,sendastoolsampleforClostridiumdifficiletoxinassayandroutine
microbiologicculture.Laboratorystudiestobeconsideredincludeacompletebloodcell(CBC)count
withdifferentialerythrocytesedimentationratelevelsofalbumin,glucose,calcium,magnesium,
phosphate,andBUN/creatinineelectrolytestatusandapregnancytestinfemalesofchildbearing
age.

PatientswithacuteseverecolitisaretreatedwithIVcorticosteroids.Antibioticsarenotroutinelyused
butmaybeindicatedinselectpatients.Electrolytecorrectionand,potentially,bloodtransfusioncan
beadministeredifindicatedonthebasisoflaboratoryfindings.TheIBDSydneyOrganisationandthe
AustralianInflammatoryBowelDiseasesConsensusWorkingGrouprecommendationsincludethe
followingforpatientswithacutesevereulcerativecolitis[102]:

Hospitalization
Unpreparedflexiblesigmoidoscopytoassessseverityandexcludecytomegaloviruscolitis
Venousthromboembolismprophylaxis
IVhydrocortisone100mgtid/qidandclosemonitoring
Ifinsufficientresponsebyday3,initiaterescuetherapywithinfliximaborciclosporin
Ifnoresponsebyday7ofrescuetherapyorifclinicaldeteriorationoccurs,considercolectomy

Authorinformation

Patientswithsuspectedbowelobstructionshouldbegivennothingbymouth(NPO),exceptfor
medications.Mostpatientswithulcerativecolitismaymaintainaregular(orlowfiber)diet,unless
megacolonispresentorsurgeryisbeingcontemplated.
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Althoughacolonoscopicevaluationmayalsobecontemplated,considertheincreasedriskof
perforationinpersonswithacutecolitis.AssessandcorrecttheposthydrationCBCcountand
electrolytelevels,asindicated.Dependingontheresponsetotheinitialinterventions,advancementof
thedietmaybeconsidered.

Bythesecondorthirdhospitalday,mostpatientsshouldbeshowingclearevidenceofclinical
improvementwithIVsteroids.AssesstheelectrolytestatusifIVfluidsarestillbeingadministered.
Consideradvancementofthediet.Thecorticosteroiddosecanbetapered.Ifthepatientisnot
improving,considerothertreatmentoptionsthesemayincludehyperalimentation,othermedical
therapies,surgicalintervention,ortransfertoatertiarycarefacility.

Continuetoadvancethediet,astolerated,onhospitalday4.Continuetheswitchtooralmedications.
ManypatientswithaflareofCrohndiseaseorulcerativecolitismaybedischargedbythistime
(occasionallyevensooner)somemayrequireanotherdayofIVtherapy.

Ifnoprogresshasbeenmadeinthepatient'sconditionsinceadmission,additionaltreatmentsare
necessary,includingsurgery(seeSurgicalIntervention,below)ormoreaggressivemedical
treatments.Again,considertransfertoatertiarycarefacility.Ifthepatienthasbeenunabletotolerate
anoraldiet,initiatehyperalimentationand/orreconsidersurgicalintervention.

Mostpatientsshouldbeabletobedischargedonorbeforethefifthhospitalday.Aregulardietshould
betolerated,withsomerestrictionsifstricturesarepresent.AnESRlevelmaybeobtainedtoassistin
futurediseaseassessment,butitsresultisunlikelytoaltercurrentmanagement.

Dischargethepatientonoralmedications,withappropriatefollowupasanoutpatient,typicallywithin
afewweeks.

ManagementofRefractoryDisease
Stepdowntherapyshouldbeconsideredearlyinthemanagementofpatientswithdifficultor
refractorydisease.ThisapproachusesimmunemodifiersorantiTNFagentsearlierinthetreatment
oftheIBDpatientthanthestepupapproachdescribedearlier(seeOverviewofStepwiseTherapy,
above).

Immunemodifiers
Ifitisdifficulttoreducethedoseofcorticosteroids,ifthediseaseisrefractorytocorticosteroid
therapy,orifpatientsarecorticosteroiddependent,theuseofimmunemodifiers6MPorazathioprine
shouldbeused.Thetypicaldosingof6MPorazathioprineis12mg/kg/day.Athigherdoses,closer
monitoringiswarranted,includingmeasurementofthethiopurinemethyltransferase(TPMT)enzyme
obtaining6TGand6MMPlevelsdoingaCBCanddeterminingliver,kidney,pancreaticfunctions.

Theseagentsarenotusedforacuteflares,becausethetimefromtheinitiationoftreatmenttothe
onsetofsignificantactionmaybeaslongas23months.Responsetoimmunemodifiersmaybe
dosedependentmonitoringofbloodcountsisrequiredtoprotectthepatientfromthehematologic
toxicityassociatedwiththeseagents.

Monoclonalantibodies

Analternativeagentisinfliximab,amonoclonalantibodyagainstTNFalpha.TheFDAapproved
infliximabforthetreatmentofCrohndiseaseinJuly2005andforthetreatmentofulcerativecolitisin

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August2005.Tobeeffectiveformaintainingremission,thismedicationisgenerallyadministeredin3
dosesof5mg/kgover6weeks(atweeks0,2,and6),withmaintenancedosesevery8weeks.

Arandomized,controlledtrialdemonstratedthatadalimumabcaninduceremissioninpatientswith
Crohndiseasethatisrefractorytotreatmentwithinfliximab.[103]Thistherapyledtomucosalhealing
andareductioninhospitalizationandsurgicalintervention.Therateofseriousinfectionwas24%,
whichwasnogreaterthantherateinpatientsreceivingplacebo.[103]

NotethatinSeptember2011,theUSFoodandDrugAdministration(FDA)issuedanotification
regardingupdatestotheBlackBoxWarningfortheentireclassoftumornecrosisfactor(TNF)alpha
blockers.[104]TheadvisoryincludedtheriskofLegionellaandListeriainfections,aswellas
consistencyoftheinformationintheBoxedWarningandtheWarningsandPrecautionssections
regardingtheriskofseriousinfectionsandtheassociateddiseasecausingorganisms.[104]

Smokingcessation
AlifestylechangethatmaybenefitpatientswithCrohndiseaseissmokingcessation.Tobaccouse
hasbeenlinkedtoincreasesinthenumberandseverityofflaresofCrohndisease,andsmoking
cessationaloneisoccasionallysufficienttoachieveremissionofrefractoryCrohndisease.

ManagementinRemission
Thetopdownapproach(ie,earlieruseofimmunomodulatorsandbiologics)includestheneedfor
steroidenhancedmucosalhealingandachievesanearlierandmorecompleteremissionthanstepup
therapy.Ageneralruleofthumbisthatonceremissionisachieved,themedicationsusedtoachieve
remissionshouldbecontinued,exceptsteroids,whichshouldbetaperedoff,becausetheyhaveno
roleinmaintainingremission[105]andtheirusemayleadtodebilitatingillness,particularlyafterlong
termuse.HomeinfusionofIVhyperalimentationisbecomingincreasinglyavailableforthoserare
patientswithCrohndiseaseinwhomprolongedbowelrestisnecessary(eg,casesofsevere
fistulizingdisease).Patientswithashortbowelmayrequireprolongedhyperalimentation.

ManagementoftheOlderIBDPatient
Diseasesofthelung(primarilychronicobstructivepulmonarydisease[COPD])inCrohndiseaseare
commoncomorbidities,primarilybecauseofsmokinghowever,cardiovasculardisease,although
commonintheolderpatient,doesnothaveanydirectlinkwithIBD.IBDmayalsobeafactorinthe
treatmentofprostatecancer(toavoidrectalinjury),butisgenerallynotafactorinbreastcancer.

MostoftheconcernsregardingtheinteractionofotherdiseaseprocessesandIBDrevolvearoundthe
medicationsusedtotreatvariousconditionstherefore,thephysiciantreatingtheolderpatientmust
continuallybeawareofthepotentialformedicationinteractions.Althoughtheadventofelectronic
medicalrecordsmakesiteasiertocheckforsuchinteractions,itremainsuptothephysicianto
determinewhichinteractionsareclinicallysignificant.

Aspirinandnonsteroidalantiinflammatorydrugs(NSAIDs)arefrequentlyusedforcardiovascularand
rheumatologicdisorderstheseagentsandcyclooxygenasetype2(COX2)inhibitorsareknownto
causeflaresinIBD(notuniversally,butoftenenoughtobeclinicallyimportant).[106]

MostaminosalicylatesdonothavesubstantialinteractionswithnonIBDagents.Thesideeffectsof
corticosteroidsmaybeexacerbatedintheolderpopulation,particularlyinthosewithdiabetes,
acceleratedboneloss,andcataractformation.TheantiTNFagentsaregenerallycontraindicatedin

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patientswithcongestiveheartfailure(CHF)butcanbeusedoncetheCHFiscontrolled.Theimmune
modifyingagentshaveaclinicallyimportantinteractionwithallopurinol,asallopurinoltremendously
increasestheserumlevelsofmercaptopurineandazathioprinetothepointwheretheseagentscan
quicklymanifesttoxicity.

SurgicalIntervention
Ulcerativecolitisisasurgicallycurabledisease.However,Crohndiseasecaninvolveanysegmentof
thegastrointestinaltractfromthemouthtotheanussurgicalresectionisnotcurative,asrecurrence
isthenorm.Inaddition,repeatedneedforsurgeryandbowelresectionmayresultinshortgut
syndromeanddependenceonparenteralnutrition.

Ulcerativecolitis
Considersurgicalinterventionforpatientsinwhommedicaltherapyfails,asitiscurativeforcolonic
disease,andforthosewithcolonicdysplasiaormalignancy.[3]Approximately2530%ofpatientsmay
requireoperativemanagement.[1]Theindicationsforcolectomyarethefollowing:

Intractableinflammation
Precancerouschanges(highgradedysplasiaorprovenmulticentric,lowgradedysplasia
confirmedby2expertpathologists)
Intolerancetomedicaltherapy
Toxicmegacolon
Perforation

Thesurgicaloptionsforulcerativecolitisvary.Currently,the2mostcommonchoicesare
proctocolectomywithileostomyandtotalproctocolectomywithileoanalanastomosis.

Themostcommonoperationperformedtotreatulcerativecolitisisilealpouch/analanastomosis
(IPAA).Inthismultistageprocedure,adivertingileostomyisperformedandanilealpouchiscreated
andanastomoseddirectlytotheanus,withcompleteremovaloftherectalmucosa.Aftertheileoanal
anastomosisishealed,theileostomyistakendown,andflowthroughtheanusisreestablished.

Themajorcomplicationofthisprocedureispostoperativedevelopmentofacuteorchronicpouchitis.
Veryrarely,particularlyinthosewithapreoperativediagnosisofindeterminatecolitis,Crohndisease
ofthepouchmaydevelop.IPAAoffersanexcellentoptionforyoungerpatientswithulcerativecolitis
andconcernswithbodyimage.However,IPAAisalsoassociatedwithasubstantialrateofinfertility
(duetopelvicdissection).

Electivesurgerycansometimesbeperformedlaparoscopically.Forfulminantcolitis,thesurgical
procedureofchoiceconsistsofasubtotalcolectomywithendileostomyandcreationofaHartmann
pouch.

ApopulationbasedstudybydeSilvaetalshowedthattheprimarypredictorsofseverepostoperative
complicationsareageandmultiplecomorbidities.Furthermore,theworstoutcomesoccurredwhen
surgerywasperformed14ormoredaysafterhospitaladmissionunderemergencyconditionsin
patientswhohadnoresponsetomedicaltreatment.[107]

Forpatientswhoplantobecomepregnant,asubtotalcolectomyispreferredtoavoidthe48%
decreaseinfecunditywiththeIPAAprocedure.

Crohndisease

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SurgeryforCrohndiseaseismostcommonlyperformedinpatientswithcomplicationsofthedisease
(ie,strictures,fistulas).Approximately70%ofpatientswithileocolonicCrohndiseaserequiresurgical
intervention.[1]Ingeneral,conservativeresectionisadvocated(includingpotentialstricturoplasty,as
opposedtoresectivesurgery)topreservebowellengthincaseadditionalsurgeryisneededinthe
future.[4]

AlthoughsurgeryisanimportanttreatmentoptionforCrohndisease,patientsshouldbeawarethatit
isnotcurativeandthatdiseaserecurrenceaftersurgeryistherule.Diseaserecurrencegenerally
mimicstheoriginaldiseasepatternatthesurgicalanastomosis.Endoscopicevidenceofrecurrent
inflammationispresentin93%ofpatients1yearaftersurgery.

Insegmentalresection,asegmentofintestinewithactiveCrohndiseaseorastrictureisresected,
andtheremainingbowelisreanastomosed.Ingeneral,aslittlebowelaspossibleisresected,
becausetheriskofdiseaserecurrenceissignificant.[108]

Inpatientswithaveryshortcicatrixstricture,abowelsparingstricturoplastycanbeperformed.Inthis
procedure,alongitudinalincisionismadeacrossthestricture,andthentheincisionisrepairedwitha
horizontalsuture.Allmucosaisspared,andtheobstructionisrelieved.Asmanyas68
stricturoplastiescanbeperformedinasingleoperativesession.

Stricturoplastyisassociatedwitha68%rateofsepticcomplications(23%ofpatientsrequire
reoperation)thismaybepreventedwithoptimalpreoperativemanagementtocontrolthe
inflammatorycomponentofthestricturebeforesurgicalintervention.

Ileorectalorileocolonicanastomosisisanoptionavailabletosomepatientswhohavedistalilealor
proximalcolonicdisease.Inpatientswithsevereperianalfistulas,adivertingileostomyorcolostomy
isanoption.Inthisprocedure,thedistalcolonisdefunctionalizedandatemporaryileostomyor
colostomyiscreated.Theileostomyorcolostomyisthentakendownafter6monthsorlonger.Many
patientswhopursuethisoptionchoosetoforegoreanastomosisafterplacementofastomaanda
consequentimprovementinqualityoflife.Approximately50%ofpatientswhohavethe
reanastomosisperformedhaverecurrencesofperianaldisease.

Symptomaticenteroentericfistulasaregenerallyresected,althoughrecurrenceiscommon.
Postoperativemedicaltherapyoftenpreventsrecurrence,althoughdataarelackingregarding
efficacy.Ametaanalysisof9randomizedtrialssuggestedthat5ASApreparationsprovideavery
modestbenefitformaintenance.[86]Thepreferredprogramofpreventionvariesbetween
immunomodulatorsandbiologictherapy.

Contraceptionintheperioperativesetting
Beforeundergoingmajorelectivesurgery,womenwithIBDshouldstopusingcombinedoral
contraceptionforaminimumof4weeksbeforethesurgery,andalternativemethodsofcontraception
shouldbeused.[109]Adviseeachpatientwhenoralcontraceptioncanberestarted.

IfawomanwithIBDisconsideringsterilization,counselherandherpartnerregardingalternative
contraceptivemethods(eg,longactingreversiblecontraception,vasectomy).Notethatinwomenwith
ahistoryofpelvicorabdominalsurgery,laparoscopicsterilizationmaynotbeconsideredan
appropriatecontraceptivemethod.[109]

Taperingcorticosteroidsinthepostoperativesetting

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Ifpossible,theuseofcorticosteroidsshouldbeminimizedbeforesurgery.Poorpostoperative
outcomeshavebeenassociatedwithprednisonedosesgreaterthan30mg/day.[1]

TheWorldGastroenterologyOrganization(WGO)recommendationsfortaperingcorticosteroids
dependonthedurationofcorticosteroiduse,asfollows[1]:

Lessthan1month:abruptcessationpostoperativelyisallowed
13months,withadoseof20mg/dayorgreater:taperby5mg/dayperweekaftersurgery
36months:taperby2.5mg/dayperweek
Morethan6months:taperslowly,at1mg/wkorlessoncethedoseis10mg/day

Diet,LifestyleModifications,andActivity
Noknowndietaryorlifestylechangespreventinflammatoryboweldisease(IBD),andnoknown
dietarysubstanceshavebeenconsistentlyshowntocauseactivationofIBD.Tobaccousehasbeen
linkedtoincreasesinthenumberandseverityofflaresofCrohndisease,andsmokingcessationcan
helpachieveremissioninpatientswithCrohndisease.Lactoseintoleranceiscommoninpersonswith
CrohndiseaseorulcerativecolitisandcanmimicsymptomsofIBD.

Diet
Althoughdiethasbeenwelldemonstratedtohavelittleornoinfluenceoninflammatoryactivityin
personswithulcerativecolitis,itmayinfluencesymptoms.Forthisreason,patientsareoftenadvised
tomakeavarietyofdietarymodifications,especiallyadaptationofalowresiduediet,althoughthe
evidencedoesnotsupportalowresiduedietasbeneficialinthetreatmentofulcerativecolitis.Sucha
diet,however,mightdecreasethefrequencyofbowelmovements.

Unlikeinpatientswithulcerativecolitis,dietcaninfluenceinflammatoryactivityinpersonswithCrohn
disease.Nothingbymouth(NPO)canhastenthereductionofinflammation,asmaytheuseofaliquid
orpredigestedformulaforenteralfeeding.Althoughametaanalysisin1995demonstratedthat
steroidsweresuperiortoliquiddietaloneforCrohndisease,aliquiddietseemedsuperiortoaregular
dietforreducinginflammation.Theproblemwithusingenteralliquiddiets,especiallythepredigested
formulations,isthatpalatabilitylimitstheintakeofadequateenergy(calories)tomeetpatient
requirements.Parenteralalimentationmaybeneeded.

Inaprospectivestudyof56patientswithquiescentCrohndiseaseonmaintenanceinfliximabtherapy
(5mg/kg,q8wk),Yamamotoetalfoundthatconcomitantenteralnutritiondidnotsignificantly
improvethemaintenancerateofclinicalremissioninpatientswithCrohndisease.[110]Inthestudy,32
patientsreceivedconcomitantenteralnutrition(elementaldietinfusionatnightalowfatdietduring
theday),and24patientsdidnotreceiveenteralnutritionandhadnodietaryrestrictions.[110]

MultivitaminsupplementationisrecommendedinpatientswithIBD.[1]ForpatientswithvitaminsB12
orvitaminDdeficiency,supplementationofthesevitaminsshouldbegiven.Theresultsof2studies
suggestthatthelinkbetweenvitaminDandIBDmaybeofparticularimportance.[111,112,113]

Inoneofthestudies,3217patientswithCrohndiseaseorulcerativecolitisandlowvitaminDlevels
hadanincreasedriskofsurgeryandhospitalization.[112]Crohndiseasepatientswith25
hydroxyvitaminDlevelslowerthan20ng/mlhadanincreasedriskofsurgeryandIBDrelated
hospitalizationthanthosewithlevelshigherthan30ng/ml.Similarestimateswereseenforulcerative
colitis.Intheotherstudy,Crohndiseasepatientswhotook2000IUofvitaminDdailyfor3months
gainedmusclestrengthandimprovedqualityoflife.[113]

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PatientsreceivingsteroidtherapyshouldreceivevitaminDandcalciumsupplementation.Parenteral
iron(IMweeklyorIV)maybeusedinpatientswithchronicirondeficiencyanemiawhoareunableto
toleratetheoralformulation.[1]

Activity
Generally,patientsdonotneedtolimitactivitywhenIBDisquiescent.Duringdiseaseflares,physical
activityislimitedonlybytheextentoffatigueandtheabdominalpainordiarrheathepatientis
experiencing.Whenabdominalpainpersistsbeyondmedicaltherapyinducedresolutionoftheactive
inflammation,othercausesofpainmustbeconsidered,includingabscess,stricture,nephrolithiasis,
IBS,andpsychiatricdisease.

Inmostinstances,diarrhealimitsactivityprimarilybecauseofthelackofimmediateaccesstotoilet
facilitiesinmanylocationsand/oroccupations.Dehydrationmaybeanissue,oftenrequiringIV
hydrationortheuseoforalrehydrationsolutions.

Moderatetovigorousphysicalactivityforaslongas12weekshasbeenshowntoimprovesymptom
scoresandmanyspecificqualityoflifedimensions,includingenergy,sleep,emotion,andphysical
functioning.[114]Thisdegreeofactivitywasdefinedas2060minutesofintenseexercise35daysper
week.Theimprovementsoccurdespitelackofchangeinbodyweight,oralanaltransittime,bowel
movementsperweek,orstoolconsistency.Thisstudyalsohighlightsthatsymptomaticdeteriorationis
morelikelyinphysicallyinactiveindividuals.

ReproductionandPregnancy
Cliniciansareadvisedtoreviewtheprescribinginformationformedicationsinwomenwhoare
attemptingtoconceive,arepregnant,orarebreastfeeding.[109]Alloftheaminosalicylates
(sulfasalazine,mesalamine,olsalazine,balsalazide)andcorticosteroidsappeartobesafeinwomen
inallphasesoffertility,pregnancy,andlactation.Menshouldavoidsulfasalazineduringperiodswhen
theyandtheirmatesareattemptingtobecomepregnant.

Reproduction

InwomenwithIBD,fertilityisnormaloronlyminimallyimpaired.Themajorityofcasereportsand
smallseriesshownoadverseoutcomesofpregnanciesinpatientswithIBDwhoaretakingimmune
modifiers.Birthdefectshavenotbeenreportedataratehigherthanthatofthegeneralpopulation.If
apatientistakinganimmunemodifierandbecomespregnant,currentdatasupporttheconsensus
thatcontinuingtheimmunemodifierthroughoutthepregnancyisthesafestcourseofactionforboth
themotherandthefetus.[115]

Theonlyagentthatiscontraindicatedinwomenconsideringpregnancyismethotrexate(MTX),which
hasdemonstratedteratogeniceffects.MTXshouldbediscontinued3monthspriortoplanned
conception.

FormenwithIBD,sulfasalazinecandecreasespermcountsandspermmotility,causingafunctional
azoospermiatheotheraminosalicylatesdonothavethiseffect.Thespermeffectsarereversibleby
discontinuingthesulfasalazine.Nofirmevidenceindicatesthattheuseofimmunemodifiersinthe
fatherleadstoincreasedbirthdefects,althoughthishasbeensuggestedinoneSpanishstudy.

Pregnancy

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MostinfantsborntoparentswithIBDarehealthy.Theprevalenceofprematurity,stillbirth,andbirth
defectsissimilartothatinthegeneralpopulation.Theprevalenceofspontaneousabortionisslightly
higherinpatientswithIBD(12.2%)thaninthegeneralpopulation(9.9%).Previousproctocolectomy
orileostomyisnotanimpedimenttosuccessfulpregnancyhowever,controversyexistsregardingthe
typeofdelivery(cesareanorvaginal)thatismostappropriatewhenawomanhashadileal
pouch/analanastomosissurgery.[109]Womenwhohaveundergonesuchaprocedureshouldconsult
withtheirobstetriciansandgastroenterologists.[109]

Theaminosalicylates,includingsulfasalazine,aresafeduringpregnancy.Folatesupplementsshould
betaken.Corticosteroidsarealsosafe,butifhighdosesareneededneartheendofthepregnancy,
monitortheinfantforsignsofadrenalsuppression.Continuationofimmunemodifiers(ie,6MP,
azathioprine)appearstobesafeinpregnancy,[106,116]aswellasmetronidazole(Flagyl)and
ciprofloxacin(Cipro).

ItisconsideredsafetocontinueTNFalphainhibitorsduringpregnancy(FDAcategoryB),but
concernshavebeenraisedabouthighlevelsofmaternallyadministeredantiTNFagentsbeingfound
inthefetalcirculation.[117,118,119,120]Themanufacturersofinfliximabandadalimumabrecommend
thatthese2agentsbediscontinuedduringthethirdtrimesterofpregnancy,althoughthereisno
documentationoffetalharm.Certolizumabdoesnotcrosstheplacenta.[117,118,119,120]

Inaretrospective,multicenterstudy,treatmentofIBDwiththiopurinesandantiTNFalphadrugsdid
notincreasetheriskofcomplicationsduringpregnancyorneonatalcomplications.[121]Therateof
unfavorableGlobalPregnancyOutcomeandtherateofneonatalcomplicationswerelowerin
pregnantwomentreatedwiththiopurinesalonethaninthoseexposedtoantiTNFalphadrugsor
thosenotexposedtoeithergroupofagents.

Effectivecontraceptionmustbeusedwithcertaindrugtherapy.[109]Bothmaleandfemalepartners
receivingmethotrexateshoulduseeffectivecontraceptionforaminimumof3monthsfollowing
treatmentwiththisagent.

Otherconcernsthathavebeenraisedincludethepotentialreductionoffertilitywithtotalabdominal
colectomywithilealpouch/analanastomosis(IPAA)surgery(primarilybecauseofadhesions).[122,
123] Thispossibilitycanlikelybeavoidedbyusingalaparoscopicapproach,andifinfertilityoccurs,
fertilitycanoftenbenormalizedbylysisofadhesions.

AccordingtotheFacultyofSexualandReproductiveHealthcareClinicalEffectivenessUnitinthe
UnitedKingdom,womenwithIBDshouldplanforconceptionwhentheirdiseaseisstableandwell
controlled.[109]Maleandfemalepatientsrequireprepregnancycounselingtohelpthemwiththebest
managementoftheirconditionbeforeconceptionoccurs.[109]

Contraceptionprecautions

AdvisewomenwhohaveCrohndiseasewithsmallboweldiseaseandmalabsorptionthatoral
contraceptionmayhavereducedeffectiveness.[109]Additionalcontraceptionisrecommendedfor
womenoncombinedhormonalcontraceptionwhoarealsoreceivingantibioticregimensforlessthan
3weeks,aswellasfor7weeksfollowingcessationoftheantibiotic.Notethatcertainmedications
prescribedforrectalorgenitalusemayadverselyaffecttheefficacyofcondoms.[109]Inaddition,
considerwhethercontraceptiveagentsmayhaveaneffectondiseasesassociatedwithIBD(eg,
osteoporosis,venousthromboembolism,primarysclerosingcholangitis).

InwomenwithIBDwhowillundergomajorelectivesurgery,combinedoralcontraceptionshouldbe
discontinuedforaminimumof4weeksbeforetheprocedure.[109]Thesewomenshoulduse
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alternativecontraception.

Breastfeeding
Sulfasalazinemetabolitescanbedetectedinthebreastmilk.Lowconcentrationsofmesalamineand
higherconcentrationsofitsmetabolitescanalsobedetectedinbreastmilk,butthesignificanceofthis
isunknown.Inaddition,corticosteroidscanalsobedetectedinbreastmilk.

Immunemodifiersareexcretedinbreastmilkandshouldbeconsideredonlyonacasebycasebasis
eithertheimmunemodifiershouldbediscontinuedortheinfantshouldbebottlefed.

Antibiotics(metronidazole[Flagyl],ciprofloxacin[Cipro])shouldgenerallybeavoidedduringlactation,
becausetheyareexcretedinbreastmilkeitherbreastfeedingorthedrugsshouldbediscontinued.
Theseagentsareprobablysafeforfertilityandduringpregnancy.

AntiTNFagents(ie,infliximab,adalimumab)traversetheplacenta,whereascertolizumabdoesnot,
becauseoftheabsenceoftheFcfragment.Theyarefoundinthecordbloodbutnotinbreastmilk.

Althoughsmallamountsofthetopicalagentsareabsorbedandthusmaybeexcretedinbreastmilk,
theconcentrationsaremuchlowerthanthosewiththeoralformsofthesamemedications.These
medicationsareprobablyreasonablysafeinbreastfeeding.

Consultations
Inpatientswithsevereinflammatoryboweldisease(IBD),withcomplicationssuchasstricturesor
fistulas,andwithflaresrequiringhospitalization,consultationwithasurgeonisoftenrequired.Early
consultationwithasurgeonisparticularlyimportantinpatientswithseverediseaseorextraluminal
complications,becausedelayedsurgerycanbeassociatedwithpooreroutcomes.

Aninterventionalradiologistmaybeconsultedwhenpercutaneousdrainageofanabscessisdesired.
Specialtyconsultationisbestformanagingextracolonicmanifestations(ie,uveitis,arthritis,dermatitis,
sclerosingcholangitis).Alsoconsiderarrangingconsultationsforpatientswitharegistereddietitian
andastomanurse,ifindicated.

Medication

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