Conclusion:Therewasnodifferenceinresponsebetweentheanti-TNFagentsused;abetter responsewasnotedinthosewhousedanti-TNFincombinationwithazathioprine,among women,inthoseunder40yearsandinthos
Trang 1Journal of Coloproctology
w w w j c o l o r g b r
Original article
disease
Universidade Federal de Mato Grosso do Sul (UFMS), Campo Grande, MS, Brazil
a r t i c l e i n f o
Article history:
Received25February2014
Accepted15May2014
Availableonline14June2014
Keywords:
Crohn’sdisease
Infliximab
Adalimumab
Perianalfistula
Age
a b s t r a c t
Introduction:The fistulizing form of Crohn’s disease (CD) represents a great challenge regardingtreatment,especiallyperianalfistulas,foritshighprevalence
Objective:Toassessfactorsrelatedtotheresponsetosurgicaltreatmentassociatedwith anti-TNFinpatientswithCDandperianalfistulas
Method:RetrospectivestudyofpatientswithCDandperianalfistulaswhousedIFXorADA
inassociationwithsurgicaltreatment
Results:30patientswithameanageof35yearswerestudied;16weretreatedwithADA(9 ADA+AZA)and14withIFX(10IFX+AZA);tenofthosetreatedwithADAresponded,and
ofthesixnon-respondents,onlyonerespondedtoIFX;eightrespondedtoIFX,andamong thosenon-respondents,nooneshowedresponsewithADA;amongtherespondents,there were10menandninewomen;ofthosenon-respondents,eightweremenand3women;
ofthoseunder40years,16respondedcomparedwithonlythreenon-respondents;ofthose over40years,threerespondedversuseightnon-respondents;astothetimeelapsedbetween theonsetofthediseaseandthebeginningofanti-TNF,14(<2years),one(2–5years)and four(>5years)responded,andfive(<2years),four(2–5years)andtwo(>5years)were non-respondents
Conclusion:Therewasnodifferenceinresponsebetweentheanti-TNFagentsused;abetter responsewasnotedinthosewhousedanti-TNFincombinationwithazathioprine,among women,inthoseunder40yearsandinthosetreatedwithintwoyearsoftheonsetofthe disease
©2014SociedadeBrasileiradeColoproctologia.PublishedbyElsevierEditoraLtda.All
rightsreserved
E-mail:chenriquems@yahoo.com.br(C.H.M.dosSantos)
http://dx.doi.org/10.1016/j.jcol.2014.05.001
2237-9363/©2014SociedadeBrasileiradeColoproctologia.PublishedbyElsevierEditoraLtda.Allrightsreserved
Trang 2Comparac¸ão entre Adalimumabe e Infliximabe no tratamento das fístulas perianais na Doenc¸a de Crohn
Palavras-chave:
Doenc¸adeCrohn
Infliximabe
Adalimumabe
Fístulaperianal
Idade
r e s u m o
Introduc¸ão: AformafistulizantedaDoenc¸adeCrohn(DC)apresentaumgrandedesafio quantoaoseutratamento,especialmenteasfístulasperianaispelasuaaltaprevalência
Objetivo: Analisarosfatoresrelacionadosàrespostaaotratamentocirúrgicoassociadoao anti-TNFdepacientescomfístulasperianaisporDC
Método:EstudoretrospectivodepacientescomfístulasperianaisporDCquefizeramusode IFXouADAassociadoaotratamentocirúrgico
Resultados:Foramestudados30pacientescommédiadeidadede35anos;16foramtratados comADA(9ADA+AZA)e14 comIFX(10IFX+AZA);10dostratadoscomADAtiveram resposta;edosseisquenãoresponderam,apenasumteverespostacomIFX;oitotiveram respostacomIFX;edosquenãoresponderam,nenhumapresentourespostacomADA;dos queresponderam,10eramhomensenovemulheres;dosquenãoresponderam,oitoeram homensetrêsmulheres;daquelescommenosde40anos,16responderamcontraapenas trêsquenãoresponderam;doscommaisde40anos,trêsresponderamcontraoitoquenão responderam;quantoaotempodecorridoentreoiníciodadoenc¸aeoiníciodoanti-TNF,
14(<2anos),um(2-5anos)equatro(>5anos)responderam,ecinco(<2anos),quatro(2-5 anos)edois(>5anos)nãoresponderam
Conclusão: Nãohouvediferenc¸aderespostaentreosagentesanti-TNFutilizados;houve melhorrespostanosqueutilizaramanti-TNFem associac¸ãocomazatioprina,entreas mulheres,nospacientescommenosde40anosenaquelestratadoscomatédoisanos
doiníciodadoenc¸a
©2014SociedadeBrasileiradeColoproctologia.PublicadoporElsevierEditoraLtda
Todososdireitosreservados
Introduction
Initself,Crohn’sdisease(CD)constitutesamajorchallenge
forthephysiciantreatinginflammatoryboweldiseases.Those
caseswithfistulizing disease,particularly perianal fistulas,
becomeevenmorechallenging,asthereisgreatdifficultyin
achievingitscontrolinthelong-term,evenwiththe
therapeu-ticadvancesmadeinrecentyears.1
Todayweknowthatthe besttherapeuticoptionforthis
presentationofCD istheassociation ofsurgicaltreatment
withthe useofanti-TNF agents, andin thissense,
“surgi-caltreatment”isnottheclassicfistulotomyorfistulectomy,
butsuccessivecurettagesandsetonplacements,allowingthat
thebiologicalsactinthehealingprocesswithoutformationof
abscesses.2
Theconventionaltreatmentofperianalfistulasinpatients
withoutCDproducesexcellentresults;butinpatientswith
CDonecannotemploytheusualtechniquesinmostcases,
giventhe highprobabilityofdevelopingfecalincontinence
Thissituationchangedpositivelywiththeemergenceof
bio-logicalagents,whichsignificantlychangedthetreatmentof
thisdisease
Atthebeginningoftheuseofbiologicalagents,anincrease
intheincidenceofperianalabscesseswasalsonoted(because
oftheexternalorificeclosurebythedrug),butovertimeitwas
foundthatthecombinationofbiologicalswithfrequent
curet-tageoffistulasandsetonplacementconstitutedaneffective
strategy,havingbecomethestandardtreatmentforperianal
fistulasinpatientswithCD.3
Whatisbeingdiscussedtoday,infaceoftheinexistence
ofclearscientificevidence,iswhethertherearedifferences betweentheavailablebiologicals,especiallyadalimumaband infliximab,whicharethemostusedinBrazil.Thus,theaim
ofthisstudyistocomparethesetwoagentsastothe differ-encesinresponsetotreatmentwithanti-TNFassociatedwith surgicaltreatmentinCDpatientswithperianalfistulas
Objective
To assess factors related tothe responseto surgical treat-mentassociatedwithanti-TNF(adalimumabandinfliximab)
ofpatientswithperianalfistulasinCrohn’sdisease
Method
Aretrospectivestudyofmedicalrecordsofpatientsfromthe InflammatoryBowelDiseasesOutpatientClinic,Hospital Uni-versitarioMariaAparecidaPedrossian,UniversidadeFederal
deMatoGrossodoSul,fromtheHospitalRegionaldeMato GrossodoSul,andfromtheprivatepracticeoftheauthor Patients withperianal fistulasand Crohn’sdisease with prescription and who made use of anti-TNF agents were included.Allpatientsincludedwerepreviouslyinvestigated forpresenceofTBandHepatitisB
Thestudyperiodwasfrom June2000toJuly2013 Anti-TNFagentswereusedatrecommendeddosesandintervals: infliximab(IFX)5mg/kgatweeks0,2and6withmaintenance
Trang 310
Fig 1 – Anti-TNF agents used according to the preference of
the patient.
every8weeks,andadalimumab(ADA)160mgatweek0,80mg
atweek2andthen40mgevery2weeks
Allpatientsweretreatedbycurettageandsetonplacement,
withsuccessivechangesifnecessary,untiltherewasthe
pos-sibilityofremovingthelesion.Onaverage,thebeginningof
thebiologicaltherapyoccurredoneweekaftersurgery
Absenceofpainanddischargeformorethansixmonths
wasconsideredasasatisfactoryresponsetotreatment
TheresultswerestatisticallyanalyzedbyStudent’sttest
andchi-squaredtest,andP<0.05wasconsideredstatistically
significant
Results
30patients (18male and12 female)were studied.Theage
rangedfrom16to58years,withameanof35years
Thechoiceofananti-TNFagentwasbasedonthe
availabil-ityandpreferenceofpatients,similarlytothedatafromthe
literatureonthesubject.4,5Ofthe30patients,16weretreated
withadalimumaband14withinfliximab(Fig.1
Theperiodofuseoftheseanti-TNFagentsrangedfrom3
to30months,withameanof18months
Ofthose16patientsusingADA,ninewerealsotreatedwith
azathioprine(AZA),whileofthose14whoweretreatedwith
IFX,10alsousedAZA
InthegrouptreatedwithADA,10hadresponseand
con-tinued their treatment Of the six non-respondents, three
stoppeditsusealtogetherandthreeothersstartedusingIFX
Ofthese,onlyonehadaresponse,remainingonthis
medica-tion.InthegrouptreatedwithIFX,eightresponded.Ofthose
six non-respondents, one stopped using anti-TNF and the
otherfivestartedusingADA.Ofthese,noonehadaresponse
andtheanti-TNFtreatmentwasdiscontinued(Fig.2
Therewasno differenceinourresultswhencomparing
anti-TNF agents(P=0.22) However,it became evidentthat
thecombinationofanti-TNFwithAZA wassuperiorversus
monotherapywiththisagent(P=0.01)
When analyzing the resultsaccording togender, it was
observedthat10menversusninewomen(P=0.13)responded,
whereas eight menversus three women(P=0.03) failed to
respond(Fig.3
Whentheresultsoftreatmentofperianalfistulas
accord-ingtoagewereanalyzed,weobservedthatyoungerpatients
hadbetterresponseversusolderparticipants(P=0.00002).Of
7.00
5.25
3.50
1.75
0
Non-respondents Respondents
Fig 2 – Comparison between patients treated with infliximab and adalimumab, combined or not with azathioprine, in CD patients with perianal fistula.
thoseagedlessthan40years,16respondedversusthree non-respondents, whileinthose agedmorethan40 years,only threerespondedversuseightnon-respondents(Fig.4
Intheanalysisoftheresponsetotreatmentwithanti-TNF
inrelationtothetimeelapsedbetweenthediagnosisof peri-analfistulainCDpatientsandthebeginningofthetherapy withthebiologicalagent,itwasfoundthat19patientsstarted anti-TNF therapy beforetwo yearsofdisease, fivepatients betweentwoandfiveyears,andsixpatientsaftermorethan fiveyearsofdiagnosis
Ofthosewho started thetreatmentwithintwoyearsof diagnosis,14respondedversusfivenon-respondents/withlost response.Ofthosetreatedfromtwotofiveyearsofdiagnosis, onlyoneresponded,whilefourwerenon-respondents/with lostresponse.Inthegrouptreatedwithanti-TNFmorethan fiveyearsafterdiagnosis,fourshowednoresponseversustwo respondents(Fig.5
Women Men
Non-respondents Respondents
10.0
7.5
5.0
2.5
0
Fig 3 – Comparison between genders as to response to anti-TNF therapy in patients with CD and perianal fistula.
Trang 415
10
5
0
Non-respondents/with lost response
Respondents
Fig 4 – Evaluation of response to anti-TNF in the treatment
of anal fistulas in CD patients according to age.
Discussion
A recent Brazilian publication on the epidemiology of CD
showedthathalfofpatientstreatedwiththebiologicalagent
presented perianal disease, mainly perianal fistulas,
high-lightingtheimportanceofthisformofthediseaseandthe
needforaneffectivetreatment.1
Inastudyofgreatrelevanceonthissubject,Sandsetal.6
observedthatonly36%oftheirCDpatientswithfistulas
main-tainedresponseafter54weeksofIFXuse.Thisdemonstrates
that,despitethegreatcontributiongivenbythebiologicalsto
thetreatmentofCD,particularlyinthefistulizingvariety,the
majorityofpatientsstilldonotachieveasatisfactoryresponse
withthistherapy.Althoughthedesignofthisarticledoesnot
allowadirectcomparisonwiththeSands etal.paper,6 we
observedacompleteresponsein60%ofcases
Thoseindividualswhoshowagoodinitialresponseto
bio-logicalsusuallykeepitovertime.7Thisfactwasalsoobserved
Non-respondents/with lost response
Respondents
15.00
11.25
7.50
3.75
0
Fig 5 – Evaluation of response to anti-TNF therapy in CD
patients with perianal fistula in time elapsed between
diagnosis and the use of a biological agent.
inthepresentstudy.TheCHARMstudyalsoshowedefficacy
ofADAin33%ofcasesofperianalfistulasatweek56,afinding verysimilartothatpresentedinthestudyofSandsetal AlthoughtheCHOICEstudyhasshownencouragingresults regardingtheuseofADAinpatientsthatfailedwithIFX,the same could notbeobservedinthepresent study.Lichtiger
et al observed that 39% of patients who had failed with IFX were successfulin the healingofperianal fistulas and improved their quality oflife In ourstudy, onlyone non-respondentpatientwithADAwassuccessfulwithIFX.8 There are many publications on this subject, several of themofgreatconsequence,butthereisashortageofarticles evaluatingotherfactorsinvolvedintheresponseto biologi-calagentsinCDpatientswithperianalfistulas.Itseemedto
usquiteinterestingtonotethatwomenhadlesstreatment failuresversusmenwiththeuseofbiologicals.Inthemedical literature,thereislittleinformationonthissubject
Inthepresentstudyweobservedabetterresponseinthe youngergroupofpatients,butthereisnosimilarevidencein theliterature.Weissetal.9foundnodifferenceinresponseto treatmentwithanti-TNFastotheageofpatientsinarecently publishedstudy,inwhichtheseauthorsanalyzedthisvariable
inrelationtoagegroup
Currently,thetimeelapsedbetweentheonsetofsymptoms
ofCDandthetreatmentwithanti-TNFhasbeenvalued,since theshorterthistime,thebettertheresponsetothetherapy.10 Thesamephenomenonwasobservedinthepresentstudy, giventhatthegrouptreatedatlessthan twoyearsof diag-nosisobtainedbetterresultsthan those treatedwithinthe periodbetween twoand fiveyears.And this second group obtainedbetterresultsthanthegrouptreatedafterfiveyears
ofdiagnosis
Conclusion
Therewasnodifferenceinresponsebetweenanti-TNFagents used;therewasabetterresponseforthosewhoused anti-TNFincombinationwithazathioprine,amongwomen,inthe groupunder40yearsandinthosetreatedwithintwoyearsof onsetofthedisease
Conflicts of interest
Theauthordeclaresnoconflictsofinterest
r e f e r e n c e s
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