using immunobiological therapy Quality of life of patients with inﬂammatory boweldisease Coloproctology Journal of

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w w w . j c o l . o r g . b r

Journal of

Coloproctology

Original Article

Quality of life of patients with inﬂammatory bowel disease using immunobiological therapy

Raphael Souza de Almeida

^∗

, Ana Carolina Ribeiro Lisboa, Alex Rodrigues Moura

UniversidadeFederaldeSergipe(UFS),DepartamentodeMedicina,Aracaju,SE,Brazil

a r t i c l e i n f o

Articlehistory:

Received14September2018 Accepted30October2018 Availableonline5December2018

Keywords:

Inﬂammatoryboweldisease Qualityoflife

Immunobiologic Crohn’sdisease

a bs t r a c t

Objectives: Toassessthequalityoflifeofpatientsdiagnosedwithinﬂammatoryboweldis- ease(IBD)usingimmunobiologicaltherapyandtorelatethegeneralanddomainscoresof theInﬂammatoryBowelDiseaseQuestionnaire(IBDQ)totheimmunobiologicaldruginuse andtheclinicalandsociodemographicvariables.

Methods:Thiswasadescriptiveobservationalcross-sectionalstudy,conductedfromJuneto September2018inatertiaryhospitalinSergipe,whichincluded47patientswithadiagnosis ofCrohn’sdisease.TheIBDQquestionnairewasappliedtogetherwithasociodemographic questionnaire,andtheclinicaldataandthehistoryofthediseasewereanalyzed.

Results:Female,mixed-race,marriedpatientsfromthecountrysideofthestateofSergipe, Brazil,whohadneverundergoneanyintestinalsurgery,representedmostofthestudypar- ticipants.24patientswereoninfliximaband23wereonadalimumab.Variablessuchas gender,typeofimmunobiologicaldruganddurationofitsuse,andassociationoftherapy withothermedicationswereshowntostatisticallysignificantlyinfluencethereportquality oflife(p-value<0.05).

Conclusion: Furtherstudieswithlargersamplesare necessaryto allowa moreaccurate delimitationoftheimpactofclinicalandsociodemographicvariablesonthequalityoflife ofpatientswithinﬂammatoryboweldisease.

licenses/by-nc-nd/4.0/).

Qualidadedevidadepacientescomdoenc¸ainﬂamatóriaintestinalem usodeterapiaimunobiológica

Palabrasclave:

Doenc¸ainﬂamatóriaintestinal Qualidadedevida

Imunobiológicos Doenc¸adeCrohn

r e su m e n

Objectivos:Avaliaraqualidadedevidadepacientesdiagnosticadoscomdoençainflamatória intestinal(DII)emusodeterapiaimunobiológicaerelacionaroescoregeralepordomínios do“Inflammatory BowelDiseaseQuestionnaire”(IBDQ)comoimunobiológicoem usoe as variáveisclínicasesociodemográficas.

∗ Correspondingauthor.

E-mail:raphael–almeida@hotmail.com(R.S.Almeida).

https://doi.org/10.1016/j.jcol.2018.10.013

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Métodos: Estudoobservacional descritivoanalíticotransversal,realizadonoperíodo de junhoasetembrode2018,emhospitalterciáriodeSergipe,queincluiu47pacientescom diagnósticodeDoençadeCrohn.FoiaplicadooquestionárioIBDQ,associadoaumques- tionáriosociodemográficoeanalisadososdadosclínicosedahistóriadadoença.

Resultados: Pacientesdosexofeminino,pardos,casados,procedentesdointeriordeSergipe equenuncaforamsubmetidosanenhumacirurgiaintestinalrepresentaramamaioria dosparticipantesdoestudo.24pacientesestavamemusodeInfliximabee23emusode Adalimumabe.Variáveiscomoogênero,tipodeimunobiológicoeduraçãodeseuusoe associaçãodaterapêuticacomoutrasmedicaçõesmostraraminfluenciaraqualidadede vidarelatada,comsignificânciaestatística(p-valor<0,05).

Conclusão:Novosestudoscomamostrasmaioressãonecessáriosparaquesepossapermitir umadelimitaçãomaisacuradadoimpactodevariáveisclínicasesociodemográficasna qualidadedevidadospacientescomdoençainflamatóriaintestinal.

licenses/by-nc-nd/4.0/).

Introduction

Inﬂammatoryboweldiseases(IBD)areagroupofdiseasesbest representedbyulcerativecolitis(UC)andCrohn’sdisease(CD).

Despitetheirhigherincidenceinmoredevelopedregions,in recentyears theyhavebecomemoreprevalent indevelop- ingcountries,whichmayberelatedtotheWesternizationof lifestyle,whichincludeschangesindietandsmoking,aswell asvariationsinsun,pollution,andchemicalexposure¹;this increasecannotbeattributedsolelytotheimprovementof diagnosticpropaedeutics.²

ThemaincurrenthypothesisforIBDetiologyemphasizes thegeneticpredispositionsinthedysregulationofthegas- trointestinalimmunesystem,alsoindicatinganinescapable inﬂuence of the environment.² The course of IBD is of exacerbation and inﬂammation remission with symptoms characterized by chronic abdominal pain, diarrhea, and weightloss.³

Treatmentisessentiallyclinicalandhasbeenevolvingin thelastdecadewiththeadventofimmunobiologicaldrugs, whicharethelastgenerationtherapeuticweaponinthetreat- ment ofIBD, reducing complications, hospitalizations, and needforsurgery.^3,4

Qualityoflifeisdeterminedbytheextenttowhichambi- tions andhopes correspondtopersonalexperience; bythe individual’sperceptionsoftheirpositioninlife,takinginto accountthecontextofcultureandthevaluesystemsinwhich thepersonlives,inrelationtotheirgoals,expectations,stan- dards,andconcepts, assessingthecurrentstateinrelation totheidealandwhattheseindividualsregardasimportant factors in their lives.^5,6 Inﬂammatory bowel diseases may hinderwork activitiesand reducesocialinteraction due to factorssuchasprofusechronicdiarrhea,asthenia,abdominal pain,hyporexia,hospitalizations,andevenadverseeffectsof medicationsusedintherapy,thusaffectingpatient-reported qualityoflife.⁷

InBrazil,thereisashortageofstudiesthatassessthequal- ityoflifeofthesepatients; thisisfurtherintensiﬁedwhen consideringtherealityofthestateofSergipe.Anotherrelevant

factoristhehighcostofdrugssuchasinﬂiximabandadali- mumab fornationalandglobal publichealthcaresystems,³ whichreinforcestheneedforstudiesthatanalyzetheirimpact onpatients’qualityoflife.

Therefore,thepresent studyaimedtoassessthequality oflifeofpatientsdiagnosedwithIBDusingimmunobiological therapy,tolistthesociodemographicaspectsofthepatients studied,andtoassociatethegeneralscoreandthedomains oftheInﬂammatoryBowelDiseaseQuestionnaire(IBDQ)with theimmunobiologicaldruginuse(adalimumaborinﬂiximab) andwiththeclinicalandsociodemographicvariablesunder study.

Methods

Thiswasanobservationaldescriptive cross-sectionalstudy, carried out fromJune toSeptember2018,atthe University HospitaloftheUniversidadeFederaldeSergipe.

Patients

Thestudyincluded47randomlychosenpatientswhometthe inclusioncriteria.

Inclusion criteria: patients diagnosed with IBD (CD or UC,diagnosedaccordingtoconventionalclinical,endoscopic, radiological,andhistologicalcriteria),⁸agedabove18years, whoagreedtoparticipateinthestudybysigninganinformed consentform,andwhowereinuseofimmunobiologicalther- apy(inﬂiximaboradalimumab),attheUniversityHospitalof theUniversidadeFederaldeSergipe.

Exclusion criteria Pregnant patients, those who were breastfeeding, those with neuromotor physicallimitations, diabetes,heartfailure,chronicobstructivepulmonarydisease, and/orhistoryofalcoholismorostomysurgery.

ThestudyfollowedtheethicalstandardssetforthbyReso- lution416/12oftheNationalHealthCouncil.Itwasapproved bytheResearchEthicsCommitteeoftheUniversidadeFederal deSergipeunderthenumber90516918.4.0000.5546.

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Qualityoflifeassessment

All interviewswere conductedbya singleinterviewer.The IBDQ questionnaire was applied to assess the quality of liferelatedtoIBDaspects.Furthermore,asociodemographic questionnairewasalsoapplied,whichincludedthemainvari- ablesofimportanceforthestudy:age,race,gender,marital status,smokinghistory,andcityoforigin.

Finally,thefollowingfactorswereanalyzedthroughclin- icaldata and the historyof the disease:immunobiological druginuse, clinical diagnosis,needforpriorsurgery,total timeofdisease,totaldurationofimmunobiologicaldruguse, locationofthe disease,andother medications currentlyin use.

TheIBDQquestionnairewasinitiallydevelopedandvali- datedinCanadain1989.⁹Itconsistsof32itemsdividedinto fourdomains:intestinalsymptoms(10items),systemicsymptoms(fiveitems),socialaspects(fiveitems),andemotional(12 items),andtheresponsesarepresentedintheformofmulti- plechoice,withsevenalternatives.Ascoreof1indicatesthe worstqualityoflifeand7,thebest.⁶Thescorereflectsthe qualityoflifeoftheposttwoweeks,sothatasimplesumof alldomainsresultsinthetotalscoreobtainedbythepatient, whichcanrangebetween32and224points.Theversionused inthis studywastranslatedandvalidated forthe Brazilian Portugueselanguagein2004,beingareliableandreproducible instrumentfortheevaluationofthequalityoflifeofBrazilian patientswithIBD.¹⁰

Statisticalanalysis

Categorical variables were described as absolute and rela- tivefrequenciesandpercentages.Continuousvariableswere described as means, standard deviations, and minimum and maximum values.Mean differenceswere tested using the Mann–Whitney test. Correlations between continuous variableswere testedand quantiﬁedusingSpearman’s correlation.Linear regressionsfor IBDQandits domains were adjustedusingtheBackwardmethodofvariableselection.The signiﬁcanceleveladoptedwas5%,andthestatisticalsoftware usedwastheRCoreTeam2018.

Results

Characteristicsofthepatientsstudied

Thestudy included47patients, allofwhomhad adiagno- sis ofCD (24 using inﬂiximab and 23 using adalimumab).

Themean age ofthe patients studiedwas 41.3 years;the youngestpatientwas19yearsold,whiletheoldestpatient was70 years old.Regarding genderand race,59.6% ofthe patientswerefemale, and59.6% declaredthemselvestobe mixed-race.Ofall patients, 55.3% were married and 53.2%

werefromthecountrysideofSergipe,while44.7%werefrom the capital, Aracaju, and 2.1% came from other states. A totalof48.9%ofthepatients hadundergone somesurgery duetoCDand29.8%declaredcurrentand/orprevioussmok- ing.

Ofthepatientsusingadalimumab,ﬁve(21.7%)hadprevi- ouslyusedinﬂiximab.Regardingthelocationofthedisease, 53.2%hadlargeandsmallintestineinvolvement.Themean time since diagnosis was of 8.1 years; in turn, the mean duration of immunobiological drug use was 39.9 months.

Other CD medications were used by 70.2%; 59.6% of the intervieweesusedazathioprine,29.8%mesalazine,and2.1%

corticosteroid.

Table 1 summarizes the clinical and sociodemographic characteristicsofthepatientsstudied.

Table1–Sociodemographicandclinicalcharacteristics ofpatientswithIBDusingimmunobiologicaltherapy.

Mean SD

Age(years)(19–70) 41.3 13.4

Timesincediagnosis(years) 8.1 6.8

Durationof

immunobiologicaldruguse (months)

39.9 32.9

N %

Gender

Female 28 59.6

Male 19 40.4

Maritalstatus

Single 16 34.0

Married 26 55.3

Separated 5 10.6

Ethnicity

White 14 29.8

Black 2 4.3

Mixed-race 28 59.6

Asian 2 4.3

NativeBrazilian 1 2.1

Origin

Aracaju 21 44.7

CountrysideSergipe 25 53.2

Otherstates 1 2.1

Immunobiologicaldruginuse

Adalimumab 23 48.9

Inﬂiximab 24 51.1

Priorsurgery 23 48.9

Smoking 14 29.8

Ifyouareusingadalimumab:

haveyouusedinﬂiximab before?

5 21.7

Locationofdisease

Smallintestine 11 23.4

Smallandlargeintestines 25 53.2

Smallandlargeintestines andperianal

11 23.4

Medication 33 70.2

Azathioprine 28 59.6

Mesalazine 14 29.8

Corticosteroid 1 2.1

N,absolutefrequency;%,percentagerelativefrequency;SD,standarddeviation;IBD,inﬂammatoryboweldisease.

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250

200

150

100

50

0

12

Sintomas Intestinais Sintomas Sistêmicos Aspectos Sociais Aspectos Emocionais IBDQ total

Fig.1–TotalanddomainIBDQscoresinIBDpatientsinimmunobiologicaltherapy.

Patient-reportedqualityoflife

TheIBDQtotalanddomainscoresare showninFig.1.The meantotalIBDQobservedinthepatientsstudiedwas163.5 points(SD=39.4);thelowestvaluewas47points,whilethe highestwas215points.

FactorsinﬂuencingqualityoflifeinpatientswithIBD

Inthestudyoftheclinicalandsociodemographicfactorsasso- ciatedwiththepatient’squalityoflife,theemotionalaspects domainoftheIBDQwasstatisticallysigniﬁcantlyassociated withgender:womenpresentedameanof54points(SD=16.5) andmen,63.8points(SD=14.3;p=0.05).Inaddition,inthe systemicsymptomdomain,patientsonadalimumab(mean:

25.9;SD=7.6)hadastatisticallysigniﬁcanthigherscorethan thoseusinginﬂiximab(mean:22.5;SD=5.2;p=0.034).Forsuch associations, the Mann–Whitney test was used. The other associationsobservedweresummarizedinTable2.

In the correlation between age, time of diagnosis, and durationofimmunobiologicaldrugusewithIBDQtotaland domain scores, using the Spearman correlation, the score intheintestinalsymptomsdomainshowedaweakpositive correlation(R=0.312;p=0.033)withdurationofimmunobio- logicaldruguse(Table3).

UsingSpearman’scorrelationandtheMann–Whitneytest, nostatisticallysigniﬁcantcorrelationwasobservedbetween IBDQtotalanddomainscoresandthevariablesage,smoking history,race,origin,diagnosistime,maritalstatus,previous surgery,locationofthedisease,anduseofothermedications, asshowninTables2and 3. However,withregardstogen- der,origin,immunobiologicaldruginuse,historyofprevious surgery,historyofsmoking,andcurrentuseofothermedi- cations,IBDQtotalanddomainscoreswere higherinmale patients,fromAracaju,usingadalimumab,withahistoryof

previousintestinalsurgery,withoutcurrentorpasthistoryof smoking,andwhowerenotusingothermedications.

After the introduction of the independent clinical and sociodemographic variablesinthelinear regressionmodels withinthe Backwardprocessofvariable selection,astatis- ticallysignificantassociationwasobservedbetweengender and scorein the emotional aspects domain (linear regres- sion coefficient – B=−9.9; p=0.011; Table 4), with women reporting poor quality of life in that domain. Statistically significantrelationshipsbetweentotalIBDQscores(B=28.7;

p-value=0.002)andinalldomains, summarizedinTable4, were alsoobservedwiththeimmunobiologicaldruginuse, sothatthescorespresentedbypatientsusingadalimumab weresuperiortothoseobservedinpatientsusinginﬂiximab.

Patients who were in use of mesalazine also presented a statisticallysignificantworsequality oflifeinthesystemic symptoms (B=−3.4, p=0.048) and social aspects domains (B=−4.5,p=0.036).Regardingthesignificantassociationfound betweenIBDQtotalanddomainscoresandrace,althoughsta- tisticallysignificantgiventhefactthatthesampleincluded onlyoneNativeBrazilianpatient,theresultsshouldberela- tivized.

Discussion

Manystudiesworldwidehaveassessedthequalityoflifeof patientswithIBD,butBraziliandataarestilllimited,particularly whenconsideringthe reality ofthestate ofSergipe.

Thestudyofthereportedqualityoflifeallowsassessingthe quality ofcare, conductingeconomic analyzesof thether- apy,anddevelopingguidelinesforclinicalpracticeandpublic policies.^9,11

Regardingsociodemographicaspects,thegenderdistribu- tionofthestudywasinaccordancewiththeliterature,asCD

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Table2–FactorsinﬂuencingthequalityoflifereportedbypatientswithIBDintheIBDQ(Mann–Whitneytest).

Intestinalsymptoms Systemicsymptoms Socialaspects Emotionalaspects IBDQtotal

Mean(SD) Mean(SD) Mean(SD) Mean(SD) Mean(SD)

Gender

Female 52.7(13.2) 22.9(6.7) 25.8(7.6) 54(16.5) 155.4(38.6)

Male 57.4(12.1) 25.9(6.3) 28.3(8.3) 63.8(14.3) 175.5(38.5)

p-Value 0.175 0.127 0.165 0.050 0.071

Maritalstatus

Single 55.1(8.6) 25.2(6.2) 28.6(6.9) 57.6(14.9) 166.4(33.4)

Married 52.8(15.3) 23.3(7) 25.7(8.1) 58.3(17.8) 160(44.2)

Separated 62.6(7.3) 25.2(6.7) 26.8(10.3) 57.6(14.8) 172.2(35.6)

p-Value 0.251 0.726 0.575 0.929 0.883

Ethnicity

White 56.5(9.7) 24.3(5.8) 28.6(7.4) 56.9(14.4) 166.3(33.4)

Black 29.5(24.7) 15(14.1) 17.5(14.8) 34(15.6) 96(69.3)

Mixed-race 57.4(10.4) 24.9(5.9) 27.3(7.5) 61.3(14.5) 170.9(33.7)

Asian 42.5(9.2) 27(11.3) 21.5(3.5) 57.5(36.1) 148.5(60.1)

NativeBrazilian 24(0) 13(0) 15(0) 30(0) 82(0)

p-Value 0.116 0.439 0.339 0.085 0.144

Origin

Aracaju 55.1(10.3) 24.5(6.3) 27.8(8) 58.3(14.2) 165.8(34.8)

CountrysideSergipe 54.4(15) 24(7.1) 26.3(7.9) 57.6(18.4) 162.3(44.1)

Otherstates 48(0) 21(0) 18(0) 60(0) 147(0)

p-Value 0.615 0.865 0.345 0.983 0.789

Adalimumab 55.6(14.4) 25.9(7.6) 28.3(7.7) 61.9(18.4) 171.7(44.2)

Inﬂiximab 53.7(11.5) 22.5(5.2) 25.3(8) 54.2(13.2) 155.7(33.3)

p-Value 0.322 0.034 0.105 0.076 0.057

Priorsurgery

Yes 55(10.2) 24.6(5.8) 27.2(7.3) 59.4(15.1) 166.1(32.3)

No 54.3(15.2) 23.8(7.5) 26.4(8.6) 56.6(17.5) 161(45.7)

p-Value 0.623 0.945 0.811 0.544 0.945

Smoking

Yes 52.4(15.4) 23.4(8.5) 26.6(9.8) 57.1(18.7) 159.4(49.4)

No 55.5(11.8) 24.5(5.8) 26.9(7.1) 58.3(15.4) 165.2(35.1)

p-Value 0.666 0.867 0.631 0.778 0.986

Ifyouareusingadalimumab:haveyouusedinﬂiximabbefore?

Yes 51.8(23.5) 21(10.8) 24.8(11.3) 59.2(22.5) 156.8(67.7)

No 56.6(11.5) 27.2(6.2) 29.3(6.5) 62.7(17.7) 175.8(36.9)

p-Value 0.870 0.190 0.400 0.843 0.986

Locationofdisease

Smallintestine 49.5(12.6) 21.6(7.1) 26.5(9.2) 51.7(16.4) 149.4(41)

Smallandlargeintestines 56.9(13.4) 24.9(6.7) 27.4(8.1) 58.6(17.2) 167.7(41.6)

Smallandlargeintestines andperianal

54.5(11.4) 25(5.9) 25.7(6.8) 62.8(12.9) 168.1(31.9)

p-Value 0.198 0.344 0.643 0.222 0.389

Medication

Yes 54(13.3) 23.5(6.8) 25.6(8.4) 57.1(16.8) 160.2(40.6)

No 55.9(12.2) 25.8(6.3) 29.5(6) 60.1(15.3) 171.3(36.7)

p-Value 0.674 0.284 0.174 0.523 0.341

Azathioprine

Yes 53(13.8) 23.4(6.6) 25.9(8.4) 57.3(16.4) 159.5(41)

No 57(11.3) 25.3(6.7) 28.1(7.2) 59.1(16.3) 169.4(37.2)

p-Value 0.260 0.334 0.445 0.719 0.375

Mesalazine

Yes 52.6(17.2) 22.3(7.7) 23.9(9.8) 54.7(18) 153.5(49.3)

No 55.5(10.7) 24.9(6.1) 28(6.8) 59.4(15.5) 167.8(34.4)

p-Value 0.995 0.295 0.219 0.403 0.378

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–Table2(Continued)

Intestinalsymptoms Systemicsymptoms Socialaspects Emotionalaspects IBDQtotal

Mean(SD) Mean(SD) Mean(SD) Mean(SD) Mean(SD)

Corticosteroid

Yes 58(0) 28(0) 33(0) 49(0) 168(0)

No 54.5(13) 24.1(6.7) 26.7(8) 58.2(16.4) 163.4(39.8)

p-Value 0.957 0.638 0.681 0.681 0.979

SD,standarddeviation;IBDQ,InﬂammatoryBowelDiseaseQuestionnaire;IBD,inﬂammatoryboweldisease.

wasmarginallymorefrequentinwomen.^1,6,7Theagerange presentedinthestudy reinforcesthe bimodalagedistribu- tion describedforCD, whichpresents aﬁrstpeak between 15and30yearsandasecondbetween50and70years.¹The higherprevalenceofmixed-raceand whiteindividualswas alsoobservedinotherstudiesconducedinBrazil⁶;nonetheless,thereisawidedebatethatethnicandracialdifferences maybemorerelatedtolifestyleandenvironmentalinﬂuences thantogeneticdifferences,²sothatthedistributionofIBDs betweenethnicgroupsremainsdynamic.¹Furthermore,most patientscamefromthecountryside,sincethisUniversityHos- pitalisastatereferenceinthemanagementofIBD,especially withregardtotheuseofimmunobiologicaldrugs.

Regardinghistoryofpreviousintestinalsurgery,therewas aslightsuperiorityforpatientswhowereneverunderwent such procedures, a ﬁnding also observed by Souza et al.

(2011),⁶Casellasetal.(2001),⁷Zhouetal.(2010),⁹andPontes etal.(2004).¹⁰ Approximatelyone-third ofthe patientshad a current or past history ofsmoking, which is considered the strongestenvironmentalfactor forIBD, particularly for cigaretteusers.SmokerswithCDhaveaworsediseasecourse than nonsmokers, with higher recurrence rates, frequent

Table3–Factorsinﬂuencingthequalityoflifereported bypatientswithIBDintheIBDQ(Spearman’s

correlation).

Correlations Age Timesince

diagnosis (years)

Durationof immunobiological druguse(months) Intestinalsymptoms

R −0.088 0.014 0.312

p-Value 0.556 0.924 0.033

Systemicsymptoms

R −0.093 0.005 0.192

p-Value 0.535 0.976 0.197

Socialaspects

R −0.018 −0.048 0.227

p-Value 0.904 0.749 0.126

Emotionalaspects

R 0.108 0.053 0.170

p-Value 0.469 0.726 0.253

IBDQtotal

R 0.004 0.015 0.268

p-Value 0.981 0.918 0.069

R,Spearman’scorrelation;IBDQ,InﬂammatoryBowelDiseaseQues- tionnaire;IBD,inﬂammatoryboweldisease.

surgical interventions,and agreater need forimmunosup- pressiveagents.¹

Most patients presenteddisease inthe largeand small intestines(53.2%),adistributiondistinctfromthatdescribed inareviewbyBaumgartandSandborn(2007),¹²whichshowed thediseaselocatedinthecolonin28%ofpatients.Nonethe- less,inthestudybyCasellasetal.(2001),⁷thelargestgroupof patientspresentedcolonandsmallbowelinvolvement,simi- larlytothepresentstudy.

Inthe presentstudy,all patientshad adiagnosisofCD, whichisduetothefactthattheBrazilianUnifiedHealthSys- tem(SUS)doesnotlistinfliximabinthetreatmentofsevere UCrefractorytocorticosteroidsandcyclosporine.¹³Theuse ofadalimumabforthetreatmentofUCisalsonotstandardin theSUS.¹⁴Slightlyoverone-fifthofthepatientsusingadali- mumabhadpreviouslyusedinfliximab;thisdrugchangewas madedueofinadequate/insufficienttherapeuticresponseto the useofthelatter. TheCHOICEstudy¹⁵ corroboratesthis changeinimmunobiologicaldrug,havingdemonstratingthe effectivenessofadalimumabinpatientswhorespondedtoit, butdevelopedintolerance,thosewhostoppedrespondingto it,andthosewhoneverrespondedclinicallytoinfliximab.Itis noteworthythat,ofthe47patientsstudied,28usedazathio- prine, ofwhom 20usedinfliximabasanimmunobiological drug.Thisisjustifiedbythesuperiorityofthecombination infliximabandazathioprinewhencomparedwiththeuseof infliximabmonotherapy,asshownbyColombeletal.(2010).¹⁶ ComparingthepresentIBDQtotalanddomainscoreswith otherBrazilianandinternationalstudiesevaluatingthequal- ityoflifeofIBDpatientsthroughthisinstrument,thescoresin alldomainsandintotalIBDQweresimilartothoseobserved byZhouetal.(2010).⁹Xuetal.(2014)¹⁷alsopresentedsimilar results,withtheexceptionoftheemotionalaspectsdomain, in which the score was over 10% higher than that of the presentstudy.Inturn,Souzaetal.(2011)⁶presentedresults over10%lowerthanthoseofthepresentstudyinthesystemic symptoms and social aspectsdomains; the other domains andthetotalIBDQscoreweresimilartothepresentfindings.

Pontes etal. (2004)¹⁰ demonstrated scoresover 10% higher thanthoseofthepresentstudyinthesocialaspectsandemo- tionalaspectsdomainsand inthe totalIBDQ;thesystemic symptomsandintestinalsymptomsscoresweresimilartothe presentﬁndings.

Among the sociodemographic and clinical factors that inﬂuencedthedomainsoftheIBDQanditstotalscore,itwas observedthatwomenpresentedlowerscoresintheemotional aspectsdomain,whichispossiblyjustiﬁedbythe factthat theyreportwith moreintensity negativeemotionssuchas sadness, fear,guilt, and shame.¹⁸ Theassociation between

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Table4–FactorsinﬂuencingthequalityoflifereportedbypatientswithIBDintheIBDQ(LinearRegressionModel).

Intestinalsymptoms Systemicsymptoms Socialaspects Emotionalaspects IBDQtotal B(95%CI) p-Value B(95%CI) p-Value B(95%CI) p-Value B(95%CI) p-Value B(95%CI) p-Value Gender

Female −9.9(−17.5to2.3)0.011

Male 1

Ethnicity

White 35.6(15.8–55.5)<0.001 15(4.1–25.9) 0.007 17.5(4–31.1) 0.011 28.9(3.3–54.5) 0.027 98.6(35.4–161.8)0.002 Black 5.5(−17.8to28.8)0.643 3.7(−9.1to16.5)0.571 4.7(−11.1to20.6)0.559 4(−25.7to33.7) 0.792 14(−60to88) 0.711 Mixed-race 37(17.4–56.6) <0.001 16(5.3–26.8) 0.003 16.6(3.2–29.9) 0.015 35(9.8–60.2) 0.006 105.3(43–167.7)0.001 Asian 21.6(−1.8to45.1)0.071 18.4(5.5–31.4) 0.005 11.4(−4.7to27.4)0.165 34.5(4.5–64.4) 0.024 80.8(6.3–155.4)0.034

NativeBrazilian 1 1 1 1 1

Adalimumab 6.3(0.5–12.1) 0.033 5.5(2.3–8.6) 0.001 5.2(1.3–9.2) 0.009 13.9(6.5–21.4) <0.001 28.7(10.3–47) 0.002

Inﬂiximab 1 1 1 1 1

Mesalazine

Yes −3.4(−6.8to0)0.048 −4.5(−8.6to0.3)0.036

No 1 1

B,linearregressioncoefficient;95%CI,95%confidenceintervals;IBDQ,InflammatoryBowelDiseaseQuestionnaire;IBD,inflammatorybowel disease.

ethnicityandthescorespresentedintheIBDQshouldberel- ativized,sincethere wasonlyoneNativeBrazilianpatient, whichdistortstheinterpretationofthedata.Regardingthe lowerscoreinthesystemicsymptomdomaininpatientsusing mesalazineassociatedwithanimmunobiologicaldrug,it is importanttonotethattheevidenceshowsonlyamarginal beneﬁtofmesalazineinCD,andsomestudieshavedemon- strateditsineffectivenessagainstplacebo.¹⁹

Furthermore,patientsusingadalimumabpresentedhigher scoresintheIBDQanditsdomainsthan thoseusinginflix- imab.The literaturedoes not present a direct comparison betweeninfliximaband adalimumab; therefore,asuperior- ityofoneovertheothercannotbesuggested.¹⁹ Inpatients whorespondedtoinductiontherapywiththeindexbiological agent,theefficacyofallagentsappearstobecomparable.²⁰ Thelargesamplessizerequiredtodemonstratedifferences betweenanti-TNFagentsmakesuchattemptsatcomparisons impracticalandunlikelytooccur.²¹

Apositivecorrelationwasobservedbetweentheduration ofimmunobiologicaldrug useand thescore intheintesti- nalsymptomsdomain,whichisinagreementwithCasellas etal.(2012),²²whodemonstrated thatalong-termeffective treatmentwithanti-TNFimmunobiologicalagentsoptimizes clinicalstatus,reducesclinicaldiseaseactivityratesand,in parallel,increasespatient-reportedqualityoflife.

Oneofthemainlimitationsofthe presentstudy isthat the sizeofthe sampleusedlimits generalizations. Further studies would thus be requiredto increase the number of patients assessed. Moreover, the disease activity was not determinedinthisstudy,whichdidnotallowestablishingdif- ferencesinreportedqualityoflifeaccordingtothephasesof activityandremissionofthedisease.Asagenericquestion- nairetoevaluatequalityoflifewasnotapplied,comparisons withthegeneralpopulationandinrelationtootherdiseases aredifﬁcult.Finally,duetoitscross-sectionaldesign,cause- consequencerelationshipscannotbedeterminedintheface

oftheﬁndings.Nonetheless,thepresentstudywasofgreat valueinunderstandingthequalityoflifeinpatientswithIBD inbothSergipestateandBrazil,stimulatingnewstudiestobe conductedinthefuture.

Conclusion

Theevaluationofpatients’qualityoflife,inadditiontobeing anexcellent clinicalassessmentinstrument,isalsoavalid methodtodeterminethetherapeuticimpactnotonlyforthe abilitytosigniﬁcantlyimprovethesymptomsofthedisease, butalsotooptimizethesocialandemotionalaspectsofIBD patients. Factorssuch asgender,type ofimmunobiological drug,anddurationofuse,aswellasotherassociatedmed- ications, showed aninﬂuence onthe quality of lifescores observedintheIBDQ,reinforcing theneedfornewstudies withlargersamplesthatcouldallowamoreaccuratedelimi- tationoftheimpactofsuchvariables.

Conﬂicts of interest

Theauthorsdeclarenoconﬂictsofinterest.

Acknowledgements

ToallemployeesoftheImmunobiologicalDrugInfusionCen- teroftheUniversityHospitaloftheUniversidadeFederalde Sergipe.

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