Journal of crohns and Cotitis (2007) 1, 77-81 ffi a v a i l a b l e a t w w w . s c i e n c e d i r ec t . c o m "lj!'s.iun."Direct ELSEVIER to treatment in inflammatorybowel Non-adherence diseasein CzechRepublic* Petr Cervenyu'*,MartinBortlikb,Jiri Vlcek', AlesKubenau,MilanLuk6sb u Department of Social ond Clinical Pharmacy, Faculty of Pharmocy in Hradec Kralove, charles University,Prague,CzechRepublic b tBDClinical Researchcenter, ISCARE Lighthouse,CharlesUniversity,Progue, CzechRepublic Received28 June 2007; accepted KEYWORDS Adherence: UtcerativecoLitis; Crohndisease; Inflammatorybowet disease; Patientcomptiance '16August2007 Abstract Objective:To assessoveratt non-adherenceto the treatment among patients with Crohns dj5ease(CD)and utcerativecotitis (UC). bowetdisease(lBD)patientswere enroLledin the study Potientsandmethods:396infLammatory their non(2OOmates,196females,210 cD, 186UC)and futfilted the questionnaireto assess adherentbehaviourduringthe treatment.The data wasanatysedusingfactor anatysis. was reportedby 32%of patients.A 12%of patients Results:overattintentionalnon-adherence reducingwasreportedby the treatment.Votuntarydose reportedtheyat teastoncediscontinued non-refillthe medicationin time. Therewere no 19%of patients.An 11%of patientsoccasionalty differencesin intentionaladherencebetweenmatesandfemales,diseasetype, previousbowel statuses.A 42%of patientsreportedunintentionaL surgery maritaL,smokingand non-smoking Factoranatysjsprovednon-adherentpatientsare more Liketyto havea higher non-adherence. ( r=0.109,p=0.008). activityof the disease is reLativetyhigh amongIBDpatientsand a The overattintentionalnon'adherence Conclusions: how to gastroenterotogist's attention shouldbe focusedon it. Our resuttsstimutatediscussion improyeeducationof the patientswith inftammatoryboweldiseaseand accentimportanceof the maintenancetherapyto them. by EtsevierB.V.AtLrightsreserved. Pubtished @2007EuropeanCrohn'sandCotitisOrganisation. 1.lntroduction i The study was fjnanciattysupportedby Ferring-L6iiva a. s. * Correspondingauthor. Heyrovskeho120350005 Hradec Kra(ov6 CzechRepubuc,Tet.: +420 495 067 251; fax, +420 495 517 266 (P Cerveny). E-moil oddress:[email protected] of inftammatorybowet disease(lBD) Pharmacotherapy phasesof the aswett asasymptomatic targetssymptomatic diseaseand may be effective in remissioninductionand papersdocumented a poor A few publ,ished maintenance.l triatsettings.l-8 rateoutsidethe cl.inical. adherence 1873-9946/5- see front matter @2OO7EuropeanCrohn'sand Cotitis Organisation.Pubtishedby EtsevierB.V Att rights reserved. doi:10.1016/j.crohns.2007.08.002 78 P. Cervenyet at. Patient'sadherenceto treatment is defined as the rate of cooperation in foLtowingthe physician'sprescriptionsand recommendations.e A sufficient adherenceis one of the key factorsof treatmentsuccess, the pubtishedpapersdocumented an increasedrisk of ftare-upamongnon-adherentpatients.3,6 Non-adherencetogicaLtymeans a lack of cooperationin fotlowingthe physician's prescriptionsand recommendations.e ln spite of progressin the pharmacotherapyin lBD, many patientsstitt ftare and non-adherence to the treatment maVbe the reasonof this.a Non-adherenceto pharmacotherapyis nowadaystaken for oneof the mostseriousprobtemsfor modernmedicineto face.e,10 The doctor patient retationship,treatment regimenand other disease-retatedfactors ptay a key role in the adherence process.The treatment duration, severat adverse effects of the medications,or symptom reduction, or even disappearance,during the remission phase ptay atso it's specific role.lo 12Besidesthis adherencerapjdty decreases with the increasingnumber of prescribedmedicinesand is atsoinverselyretated to the number of dosesper day.12,13 In our study we assessedrate and most frequent reasons of non-adherenceto the pharmacotherapyof lBD.We useda Table 1 Demographic characteristics of the examined cohort(N=396) Characteristics N (%) Mate Femate Averageoge Min. 200(50.5) 196(49.51 39.1years 18 79 Education Etementary Trained Highschoot University Status Student Working Pensioner Condition Singte Maried Widow/widower Divorced Smokers 29 (7.3) 125(31.5) 187(47.2) 5 5( 1 3 . 9 ) 18 (9.6) 271 (68.4) 87 (22.0) 139(35.2) 200(50.s) 1 1( 2 . 8 ) 4 s ( 1 .15 1 78 (19.7) Avercgeage of IBDdiagnostics MAX. Averagelength of IBD treatment Min. MAX. Fami[ior occurrenceof IBD lBD, inftammatorybowel disease. 9 79 7.4 years 1 41 63 cases(15.9) Table2 Clinicatdata of the examinedcohort lN=396) Diseasecharacteristics N (%) Crohn'sdisease Activity Remission Chronicallyactiye Ftareup Localization Terminaliteum Colon lleo-colitic UpperGIT Diseos belnviour Non-stenosing/nori-perf orating Sten6in€ Moratir€ Itedicatidl6 Anincaltl ates lmrrurE-fe5sa.tts Topicatqtideroids Systemt qtiderdds tledbtix! free 2 1 0( 5 3 . 1 ) Ulcerative a&is ActiYity Refi|isin CfYorta|ly ditE Ftarc |.p Lndifr*n Proctitis Pr.rh*!dti5 l€ft-ibd bCgrie hffitB 'brc Ani brrr| EgE*s Tqidcrh:EBrie 5t$€r-@tifisoads tffibfe 148(70.51 50 (23.8) 1 2( 5 . 7 \ 69 (32.8) 58 (27.7) 8 0( 3 8 . 1 ) 3 (1.4) 1 1 3( 5 3 . 8 ) 54125.7) 43 (20.s) '188 81 65 34 9 186 (46.e) 131(70.4) 3e (21.0) 16 (8.6) 16 (8.6) 18 (9.61 e4(s0.s) 58(r1.3) 169 25 12 28 12 GI[,gffit-nquesh-ornaiesj-e 10 gastrEisticgc! r.urg patientswith lBD,fotowed uo in cefliers in the CzechRepubtic. 2. Patiefits and rethods PatientswrJ- r€ J€€!-€ss of IBD(Crohn'sdiseaseand utcerative co{itbr- :bjo.€a -E in the gastroenterotogicatambutances,bEre e-r:!ca r :re study betweenAugust2005and -re =-ra-riDed February 2(Ecohort comprised of 396 pa:f, gar€-:erotogicaL units from attover the tients fruu CzechReg.a-- .q rEtai€d characteristicsof the examined -a6 cohort is distr4le r 1 and 2. Duringone ambutatory visit of a gasrET=D'-ti. patient was askedfor participation in tlE CJ€=[rrai.E srvey. The patients were briefty infomed dDr ds-€.rce probtemsand the study'scharacter. ]lFt €e yEe.-.€d an anonymousquestionnaire, where thet €a-rc eErs their own experience with fottowing tlF EaFt€.r{ogist's recommendationsand orders.llret E E:6-:-. 3-.a.rdnteed that no DersonaL data are Non-adherenceto treatment in inftammatory bowel diseasein CzechRepubtic 79 duringthe treatmentwas admitted by 50 patients(12.6%). The most frequent reasonswere: feeting wetl and therefore supposingthere is no needto continuewith pharmacologicaI treatment (54%)and adversedrug effects occurrence(16%). In women pregnancyor breast feeding were atsoreasonsfor intentionat treatment discontinuation(10%). At least one intentionat dose reduction without gastroenterotogist'sconsentwas in the questionnairestated by 78 respondents(19.7%).The most frequent reasonswere: feeting wett (64.1%)and runningout of the medicationand therefore a necessityto reducedosesin order to saveit titl the next visit of a gastroenterotogisr(7.9%1. Adversedrug effects occurrencewas againone of the frequent reasonsof just as pregnancy and breastfeeding dosereducing(11.5%), (3.8%). in women Forty five respondents(11.3%)admitted they minimatty once did not refitl their medicationson time. The meantime of being without the medications in these patients was 7 days. Onty 9 patients (2.2%)stated they use their medications onty when wetl feeting deteriorates and onty 2 patients (0.5%)use it just prior to visitingthe IBDUnit. No one reported comptete disregardto the prescribedtreatment. Generalty,at least one form of intentional non-adherence was stated by 129 respondents(32.5%). UnintentionaInon-adherence(occasionattyforgotten prescribeddail.ydoses)was reported by 169 patients (42.6%). As for addjtional questions, 88 patients (22.2%)stated they detected at least once an adverseeffect of the prescribed IBDtherapy drugs. In patients with CD receiving aminosaticylatesthe nonadherencerate at any timepoint was 34%vs. 40%in patients vs. 38%in patients on systemiccorti' on immunosupressants costeroidsvs. 31%in patientson topicat corticosteroids.The differenceswere statisticattyinsignificant. The non-adherencetended to increasein CDwith disease activity (30%in remissionvs. 42%in chronicattyactive vs. 42% in flare), howeverdid not reach statistical significance' Simitarstatisticattynot significantdifferenceswere found patients with lJC. The overatl non-adherenceat any time in 3. Statisticalanalysis was 32%in patients on aminosaticytatesvs.40% in those on vs, 39%on systemic corticosteroidsvs. The data was processedby the statisticat software SP55@, immunosuDressants 'l'1.5. 42%on toDical corticosteroids. For the characteristicsof the tested cohort, version The differences in activity in CD was not of statistical descriDtivestatisticswere used. significance(33%in remissionvs. 31%in chronicaltyactive vs. The / (chi square) testing was performed to compare 25%in flare). frequencies of demographicvariables and diseasecharac293 patients (73.9%)rate their treatment as quite efteristics between adherent and non'adherent groups. 44 (1'1.1%)take it for mitdty effective, 57 patients processed fective, factor anatysis, by the The interview data were (14.5%)were not abte to score it and onty 2 respondents a method that enabtesthe reduction of a large body of data (0.5%)evatuatedtheir treatment as completety ineffective. into a few independent factors. The factor analysisatlows 25.7%of lhe Datientsseek additiona[information about the the researcherto keep the maximumamountof information, prescribed drugs. As for disease,40.1%of the patients seek factors and white finding retationships between derived additionatinformation. additional variabtes.la To corretate individuaL adherence By means of 12 testing no statisticatty significant retafactors with other ctinical and demographicvariabtes, the tionshiDsin adherencebetween the two diseases,genders, Kendatt'sTau coefficient vatueswere used. <0.05 smokersand non-smokers,marital status and other demostatisticatty significant. was considered A p vatue of graphicvariabteswere found. alt tests were two-taited. to be stated and that the responsesin no way witl inftuence their further treatment options. Those who agreed with participation were enrotled. Patients were not given advancednotice about the study before visiting the IBDUnit. After agreement attending gastroenterologistprovided information about the diseasetype (CDor UC),activity, and tocatizationto the speciat protocot which was a part of the questionnaire.The disease activity was simptified for the purpose of statistical anatysisto a three-grade scate (remission,chronicattyactive, ftare). Subsequenttypatient was giventhe questionnaireto complete it. After that, he seated the questionnaire in the envetope and when leaving the ambutance, he teft it at the designated place at the reception. After termination of the study the questionnaires werecotlected from the gastrocentersandjointtyunsealedat the Departmentof Socialand CtinicaIPharmacyat the Faculty of Pharmacy.This ensuredfut[ anonymityto the patient. Key questions focused on adherence, adapted from a previouslypubtlshedpaper,l were inctuded with additionat questions to comptete a 3o-item questionnaire. The key questions on adherence targeted at treatment discontin' uation, dose reduction, regutarity in using medicines and refitling medicines. Additionat data was of demographic character, knowLedgeon diseaseand medicinesand regis' tered adversedrug effects (data not shown). In our study,patientswere consideredto be non-adherent if they stated to have at least one of the possibte nonadherent behavioursin the questionnaire:a) not using the prescribedmedicationsat atu b) usingthe prescribedmedications onty prior to visiting a gastroenterotogist;c) using the prescribedmedicationsonty when their feeting of wetl.being deteriorates; d) treatment discontinuation without consent;e) dosereductionwithout their gastroenterotogist's consent;f) not refitting their medtheir gastroenterotogist's ications on time. Prior to the study [aunchthe questionnairewas validated in the pitot group of IBDpatients, foLtowedup in the GastroenterotogicatCentre of the UniversityHospitatin Prague.s 4. Results 4.1. Factoranalysis A totat of 396 IBDpatients participated in the questionnaire survev. At least one period of treatment discontinuation The 11 questions, crucial for adherence, were proceeded usingthe factor anatysis.The four independentfactors were P. Cervenyet at. 80 Table3 Contributionsof 1'l crucialinterviewquestionsto the factors characterizingadherencein the cohort (correlationcoefficientt) tike diseasetype, previousbowet surgery characteristics werenot found' gender,maritalor smokingstatuses, 5. Discussion Factor Regutarityin using Actionafter omitted dose Omitteddosesduringtast month Treatment discontinuation Dosereducing Doseincreasjng Refillingthe medicinesin me Not refittingduringlast year Efficacyevatuation on disease Knowtedge on medicines Knowtedge 0.822 0.121 -0.043 0.090 o.T)4 0.001 0.070 -0.003 0.725 0.106 0.008 0.213 0.130 0.094 -0.1'16 0.677 0.152 0.051 0.074 0.647 0.081 0.230 0.189 0.555 0.098 0.899 0.072 0.145 0.126 0.893 0.042 0.003 o.M2 0]32 -0.099 -0.333 -0.008 0.026 0.873 0.101 0.036 -0.049 0.856 0.099 identified (Tabte3). Thesefactors can be taken for certain character traits of adherencein the examinedcohort' 1. A factor characterizinggeneral non-adherenceto treatment. A tow regutarjty in using medicinesand frequent dosesomitting is remarkabte.lt is atso characterizedby treatment discontinuation,dosesreduction and non"refittingthe medjcinesin time. Z. A fa-ctor characterizing patient's depreciation to the treatment. Non-refjtLingthe mediclnesin time and irregular usingof them is considerabte' 3. A fictor characterizing patient's consistencyin treatment. lt is characterizedby a tack of treatment discontinuation and votuntary increasein dose, when wetl feeting deteriorates. An active searchingfor additional information on medicinesand diseaseis considerabte' 4. A factor characterizingintentional non-adherenceand a tack of confidenceto the treatment' lrregularity in medicines using is considerabte,just as treatment disconti' nuation and doses reducing. A very low rating of treatment effectiveness,but an active seekingadditionat information on diseaseand medications,are remarkabte' The factors were subsequentlycorretatedwith additionat questionnaire data (personat, demographic, disease,and medication data), usingthe Kendatt'sTau coefficient vatues ,, and a signjficance Level(p vatue). Adversedrug effects occurrencepositivetycorretateswith Factor3 (r=0.119,p=0.005)andatsowithFactor4(r=0 107' p=0.011). Both factors are characterizedby active seeking additionatinformation on diseaseand medicinesby patients' Factor4, characterizingintentionat non-adherenceand a tack of confidence to the treatment, is in a positive corretationwith diseaseactivity (T=0.109,p=0'008)' Patients with a history of non-adherentbehaviourare of a higher risk of ftare-up. In addition, by means of factor anatysis, statisticatty significant retationshipsbetween non-adherenceand other lnsufficient adherenceto the pharmacotogicaItreatment of IBD may be a reasonof it's faiLure.A complicacyand comptexity of a processof patient'sadherenceto the treatment jt's research'e unabtesusinga singtemethod for papers address this propubtished previousty A few btems.l-8 ln case of studies using anatytical determination of active substanceor a metaboLitein biotogical materiat, Van Heesand Van Tongerenassessednon'adherenceto the sutfasatazinetreatment upon 12%,2Other studies anatyti' catty demonstratedthe absenceof mesataminein 12% and 7 in 13% of examinedpatient cohorts. Usingpatient medication recordsfrom the pharmacy,the wasstated at onty 40%' oercen;ee 'Patients of full.yadherentpatients were designatedas non-adherentif they used less than a0%of the prescribeddosesduring the past 6 months'4 Sewitchet at. stated intentiona[ non-adherenceat 36'5% of the examinedcohort.rShateet at. provedretrospectively ingestionof tessthan 80%of pre5cribedmedicinesin 43%of pa--tients.t35%of non-adherentpatients were identified in the study of Lopezsan Roman./ Kaneet at. suggestmate genderand singtestatus are risk In the studyof Shateet at', younger factorsfor adherence.a years' Datients, patients educated beyond the age of 16 prescribed a being emp(oyment, patientshavingfutt'time and medications no other taking regimen, three-times"a-Aay identified ferceiving their medication as ineffective, were A higher degreeof intentionalnon-ad' as non-aJherent.5 herencein the studyby Lopezsan Romanwasassociatedwith ereater patient's dePressionand patient-physician discorpatients iance, with patients having tonger'standinglBD, themconsidered who trusted their Physicianless and who treatment" their about setvesto be lessinformed Cervenyet al. proved adherencetends to decreasewith younger "ge of Patients and interestingty atso with higher education ot patients. lt was also documentedthat adverse drug effects impair patient's attitude to the treatment and subitantiatty decreaseadherenceto the treatment'8 Our study faited to prove any statisticattysignificant retagender' tionshipsbetween adherenceto the treatment and and its type disease previous surgery bowet maritai status, non-smokers' and smokers and locatization pubDifferencesin methodotogiesof our and previousty of resutts' comparison tished studies unable more detailed Anotherbarrier of comparisonis definition of non-adher' ence, that is arbitrarity set in each study' Howevergeneratty' baseduDonthe output of descriptivestatistics, we can conctude the ratio of intentionatty non-adherentpatients in our published cohort is simitar tike described in previousty the we report non-adherence, unintentionat DaDers.As for ln iaiio in our study to be smatler,than previoustypublished nonthe unintentionat our study we did not focus further on adherenie, as we assumedthis type of non-adherenceis not as riskv as the intentional one that is of greater impticatjon and needsto be addressed.T By means of factor anatysis,we faiLed to confirm that adherencerate dependson gender,diseasetyPe and other demographicvariabtes.we report a very strong inftuenceof Non-adherenceto treatment in inftammatorv bowet diseasein CzechRepubtic adverse drug effects on adherence and, contrary to previously pubLishedpapers which do not address this issue,we found it adherenceimpairing. Intentionalnonadherent behaviour due to adverse drug effects was the secondmost often reported reasonin the questionnaire.In addition, adversedrug effects were independenttyprovenby the factor analysis to affect a patient's confidence in treatment. Adversedrug effects occurrencewas frequently reported in patients activety searchingfor additional information on diseaseand medications.ln caseof medicines these information logicatty inctude those on adverse drug effects, knowtedgeof which may impair adherenceto the treatment. Patientsmay be more consciousof adversedrug effects and therefore they may observethem on themsetves. Adversedrug effects ofdrugs for IBDshoutdbe in the scopeof and shoutdbe taken accountof. a gastroenteroLogist Our another very important finding is non-adherentpa' tients are tikety to suffer from more severe disease.This confirmsresuttsof previoustypubtishedstudiesadherenceto the pharmacotherapyis important for maintainingremission in oatientswith 18D.3,6,8 Resuttsfrom factor analysis suggestadherence to the treatment in the examined cohort may be strongly inftuenced by patients knowtedgeon diseaseand pharmacotherapy.Thesefindingsopen a discussionof optimat educationof patients on these topics by a gastroenterotogist.Particutar attention shoutd be paid to information on adverse drug effects, as atsoresuttsfrom factor anatysis. Generatty,if there is a tack of a treatment success,a gastroenterotogistshoutd think among others of possibte non-adherent behaviour of a Datient. Patients shoutd be intensivetyinstructed about the importanceof maintenance therapy and adherenceto the treatment in order to achieve the therapeutic goa[ - reducedfrequencyof retapse. Our research resutts may be re(ated to the entire IBD poputationin the CzechRepubtic.The examinedcohort was formed by patients fottowed up in 10 gastroenterol.ogicat units from attover the country and the number of cohort subjectswas not inconsiderabte. 6. Conclusion At least one form of intentional non-adherencewas documented in 32.5%of the examined cohort of 396 IBD patients. The intentional non-adherenceis characterized by treatment discontinuationand dosesreduction, both withconsent.The most frequent reason out a gastroenterologist's was feeling wett. Adversedrug effects atso pl.ayimportant rote in adherenceprocess.Another important form of nonadherent behaviourby patients is that of not refilting their DrescriDtionson time. Thefactor analysisdocumenteda higherdegreeof disease activity among non-adherent patients. Adherence to the treatment was also proven to be impajred by adversedrug effects. Adherenceto the treatment seemsto be inftuencedby a Datient'sdiseaseand medication awareness,Gastroenterol- 81 ogistsshoutdeducate IBDpatients regardingthe importance of maintenance therapy and adherence to the treatment generarry. Lowering of intentional non-adherencemay be one of possibleways how to improve effectivenessof IBDtherapy. Acknowledgements To the members of The working Group for IBD in Czech Repubtic,to have madethe study possibteto be doneat their working ptaces: Pavet Kohout, MD, PhD, Prague; Otga Shonove,MD, Cesk6 Budejovice; Jana KozLuhova,MD, Plzen;LudekHrdl.icka,MD, Prague;KareLMarey,MD, Prague; Lenka Nedbatova,MD, Leberec; Michat Konecne,MD, PhD, Olomouc; Tomas Douda, MD, PhD, Hradec Kratove; Libor Buzga,MD, Ostrava;MirostavSamek,MD, Most. References 1. 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