indication for chronic idiopathic urticaria慢性特发性荨麻疹指示的otc（ppt86）课件

1 CLARITIN 10mgloratadine OTCIndicationforChronicIdiopathicUrticaria ScheringCorporationApril22 2002 2 Background JointNon PrescriptionDrugandPulmonary AllergyAdvisoryCommitteesreviewonMay11 2001 Loratadine 10mgdaily issafeforOTCtreatmentofallergicrhinitis 3 Objective Toconsiderloratadinefortreatingepisodesofchronicidiopathicurticaria CIU OTCfollowinganinitialphysiciandiagnosis 4 Agenda OverviewJohnM Clayton Ph D ClinicalOverviewofUrticariaEugeneW Monroe M D ScheringStudiesonCIUStephenNeumannRisk BenefitAnalysisandConclusionsJohnM Clayton Ph D 5 CIUasanOTCIndication In depthReviewofCIUIndicationNewStudiesCIUPatientStudyPhysicianPracticesConsumerSelf RecognitionLabelComprehensionClaritin WorldwideSafetyReviewExpertPanelReview 6 Findings CIUisgenerallynotassociatedorconfusedwithmoreseriousconditionsCIUiscurrentlymanagedbyconsumersasaself treatedconditionPhysiciansandconsumersarecomfortablewithconsumers abilitytoself recognizerecurringepisodesofCIU 7 Findings Consumersalreadyself treatwithOTCsedatingantihistaminesClaritin issafeforOTCtreatmentofCIUandprovidesabetterrisk benefitalternativeAdequatelabelingcanbedevelopedforClaritin OTCforsafeandeffectiveOTCuseinCIUfollowinganinitialphysiciandiagnosis 8 URTICARIA Hives EugeneW Monroe M D DepartmentofDermatology AdvancedHealthcareAssistantClinicalProfessor MedicalCollegeofWisconsin 9 ObjectivesofPresentation OverviewofUrticaria Hives ClassificationDiagnosticEvaluationManagementConsequencesof consumer patient misdiagnosis 10 Urticaria Hives Skinreactionpatterncharacterizedbytransient pruritic edematous lightlyerythematouspapulesorwheals frequentlywithcentralclearing 11 DifferentiatingAcutefromChronicUrticaria Hives AcuteUrticaria Hives DurationoffewdaystofewweeksIncidenceof15 20 ofpopulationEtiologyusuallydetectedMostcasesaremildandneverseenbyphysicianChronicUrticaria Hives DurationgreaterthansixweeksRangesfromcontinuous almostdaily torecurrent symptomfreeintervalsofdaystomanyweeks CoursevariablefrommonthstoyearsIncidenceofupto3 ofpopulationEtiologynotfoundin90 95 ofcases IDIOPATHIC causeunknownornotdetermined 12 PotentialCausesofUrticaria Hives DrugsFoodsInfections PsychogenicFactorsPhysicalAgentsInhalantsContactantsGeneticFactorsInternalDiseases ConnectiveTissueDisorders Vasculitis Thyroid etc MostCommonCauses OtherCauses 13 DiagnosingChronicIdiopathicUrticaria ChronicHivesofUnknownCause History PhysicalExaminationDetailedhistoryismostimportantdiagnostictestReviewofsystemsReviewofthepotentialcausesforhivesPhysicalexamLaboratoryanddiagnostictestsonlyorderedbasedoncluesfromhistoryandphysicalexamCIU aDiagnosisofExclusion 14 ManagementofAcuteUrticaria Hives EliminationorreductionofunderlyingcausePatientEducationNaturalcourseofdiseaseandetiologiesPossiblecomplicationsandassociatedconditionsandappropriateactionsDrugTherapyH1antihistamine 15 ManagementofChronicIdiopathicUrticaria Reductionoravoidanceofnon specificaggravatingfactorsPatientEducationNaturalcourseofdiseaseandetiologiesPossiblecomplicationsandappropriateactionsDrugtherapy 16 TreatmentAlgorithmforChronicIdiopathicUrticaria H1antihistamines Non sedatingpreferred H1antihistamine otherH1 H2receptorblockers inhibitorsofothermediators orinhibitorsoftheinflammatoryandcellularreactionAdditionalmedicationsareusedwhenthesymptomspersistandefficacyisnotoptimalwithmonotherapy 17 SpectrumofUrticariaPatients RangeofUrticaria hive patients amilder self limiting formtoverysevere refractory Rangeofconsumer patientparticipationwiththephysician notseeingphysician selftreatingtoactiveparticipationTreatmentofUrticariaPatientsstandardofcareH1antihistamines 18 MostLikelyConditionsConfusedorMisdiagnosedforCIU Acute ChronicUrticaria Hives Eczema ContactDermatitisAngioedema 19 ConsequencesofMisdiagnosis Vastmajorityofcasesmild self limitingAnappropriatetreatmentforacutehivesisanantihistamine AcuteUrticaria Hives 20 ConsequencesofMisdiagnosis 5 10 haveanidentifiablecausePatientswillusuallybedriventothephysiciandueto severity persistenceofitchingfailuretorespondtoself treatmentpresenceofothersignsandsymptomssuggestiveofamoreseriouscondition jointpain fever discolorationofthehivesetc ChronicUrticaria 21 ConsequencesofMisdiagnosis Mostlikelyconfusionwithother itchyrashes e g ContactDermatitis Eczema Patientswillusuallyseekaphysicianwhen changingseverity persistenceofsymptomsfailuretorespondtoself treatment Dermatitis Eczema 22 ConsequencesofMisdiagnosis Angioedema urticariacanco existandcansometimesbeconfusedwitheachotherAngioedemaaregianthivesorhivesinvolvingmucousmembranesandtissuesaroundtheeyes lipsorgenitaliaHistologicallyinvolvesdeeperlayersofskinthanurticariaAlthoughvisuallymorenoticeablethanurticaria presentnoadditionalseriousconsequencestothepatientNodifferencewithclinicaltreatment Angioedema 23 Anaphylaxis AnimmediatesystemicallergicreactionproducedbythereleaseofmediatorsfrommastcellsandbasophilsSimultaneouslyinvolvesSkinmanifestations hives Respiratorysystems dyspnea wheeze CVsystem dizziness syncope hypotension GIsystem nausea vomiting diarrhea Incidenceofanaphylaxisisrare1 2 1 Yocum RochesterEpidemologicStudy JournAllergyClinImmuno104 452 6 19992 Neugut Arch Int Med Vol 161 Jan8 2001 24 Anaphylaxis cont Chronicurticariaisnotassociatedwithnorisitariskfactorforthedevelopmentofanaphylaxis3AcuteurticariaisanassociatedsymptomwithanaphylaxisbuttherapidsimultaneousonsetofCVorRespiratorysymptomswillcausethepatienttoseekimmediatemedicalattentionRespiratoryandCardiovascularsymptomsmostalwaysoccurwithin30minutesofpresentationofthehives 3 Winbery Lieberman ImmunClinicNorthAmericaVol15no3Aug 95 25 Conclusions Cardinalfeaturesofurticaria acuteorchronic cutaneouswheals rednessanditchingDiagnosisofChronicIdiopathicUrticariaadiagnosisofexclusionbyphysiciansConsequencesofpatientmisdiagnosisrepresentsalowsafetyriskAvailabilityofOTCnon sedatingH1antihistaminesinCIU Bettersafetyprofile vs currentOTCantihistamines Createsopportunityforbettercarethroughlabelingandpatienteducation 26 ChronicIdiopathicUrticaria KeyStudiesConductedBySchering Plough 27 ScheringConductedFourStudies Understandconsumer sabilitytocomprehendcertaincommunicationspointsonthedraftlabel 28 ConsumerStudyDesign ScreeningofSubjectsInternetpanelscreenedviae mailquestionnairetoidentifyphysician diagnosedCIUsufferersQuestionPosed Haveyoueverbeendiagnosedbyamedicaldoctorashavingchronicorrecurrenthivesthathavenoknowndiscernablecause alsoknownaschronicidiopathicurticaria Re screening ValidationofSubjectsRandomsampledrawnfromCIUsamplingframeandaskedtologontoawebsitetocompleteamoredetailedquestionnaireSubjectswerere screenedforphysiciandiagnosedCIUatloginLiteratureonconsumerresearchsupportsthatmostrespondentsprovideaccurateresponsestostudyquestionsonpersonalhealthissuessuchasconditionspersonallysuffered excludingsensitivetopicssuchasSTD s 29 ConsumerStudyDesign StudyPopulationFinalsample N 388 isrepresentativeoflargerpoolofCIUrespondersandhasaprofileconsistentwithkeydemographicsreportedwithCIUFemale Middleaged 30 ConsumerStudyDesign Surveyquestionscomprisedprimarilyofavariationofclosed endedormultiplechoicetypequestionsSubjectscouldtypeinresponseswheneverpre setlistsdidnotmeettheirneedsAllkeyquestionshadthisoptionPossibleresponselistswererotatedtominimizeorderbiasinpresentationClosedendedquestionsareastandard acceptedpracticeinsurveyresearchandofferanumberofadvantagesAreagoodchoicewhentheoptionsarelimitedandcanbeforeseenPermitdirectcomparisonofresponsesfromsubjecttosubjectAddresstheissuethatmostrespondentswillnotwriteelaborateanswersAvoidinterviewerrecording probingbiasespresentinopen endsAvoiderrorsassociatedwithcoding categorizationofresponses 31 Q Inatypicalyear howmanyepisodesofchronichivesdoyouexperience 32 FrequencyofSuffering 34 42 24 Mean 3 4times N 388 CIUsufferersareexperienced frequentsufferersmakingitareadilyrecognizablecondition 3orMoreEpisodes Year66 33 Q Pleaseindicatethesymptomsyouexperiencewhenyourhivesrecur 34 SymptomsofCIU Note Responsesdonotequal100duetomultipleresponses ThereissignificantconsistencyinsymptomsdescribedbyCIUsufferersSymptomsthatcouldbeconfusedwiththemostthreateningmanifestationsofanaphylaxisarerarelymentioned N 388 35 Q Thinkingaboutwhenthehivesappearedpriortoseeingaphysician what ifanything didyoudototreatorrelievethecondition QuestioncontextispriortodiagnosisofCIU 36 ActionatInitialOccurrence Total N 388 UsedanyOTC topicalorsystemic Net 70 TookanOTCantihistaminesuchasBenadryl orChlor Trimeton 62 Usedatopicalanti itchcreamsuchasBenadryl 36 Usedatopicalanti itchlotionsuchascalaminelotion46 Note MultipleMentions Self medicationpriortophysiciandiagnosisisacommonbehaviorandOTCoralantihistaminesarecommonlyused 37 Q Inthepastyear howoftenhaveyouseenaphysicianforthiscondition 38 PhysicianCare One third 33 ofstudysubjectshavenotseenaphysicianforCIUinthepastyearNearlyone fifth 19 reportthattheyhavenotseenaphysiciansinceinitialdiagnosis Anotableproportionofpatientsarenotundercontinualcare 39 Q Whenyourchronichivesrecur pleaseindicatewhatyounormallydo 40 TypicalActionUponRecurrence N 388 Useprescribedmedicationalreadyonhand52 UseOTCmedication43Call visitphysician20Takebath soothingbath soakwashareas3Nothing waititout nolongerhaveproblem8Gotoemergencyroom1Allothermentions5 Patientsself manageCIUwiththeuseofbothprescriptionmedicationsonhandandOTCmedications Note MultipleMentions 41 PhysicianContact N 388 SubjectsWhoCall VisitPhysician20 WhenContactPhysicianEverytime4 Sometimes4 Onlywhensymptomsdon trespondtocurrenttreatments medication s 7 Onlywhenamoreserioussymptomsuchasswellingofface mouthoccurs2 Noanswer3 Mostphysiciancontactcomesaboutwhensymptomsdon trespondormoreserioussymptomsoccur 42 Q Nowthatyourconditionhasbeendiagnosedbyaphysician howeasyisitforyoutoidentifythisconditionwhenitreappears 43 AbilitytoSelf RecognizeCIU N 388 EaseofRecognitionVeryeasy80 Somewhateasy14 Very SomewhatEasy94 Neithereasynordifficult6 Somewhatdifficult Verydifficult OncediagnosedbyaphysicianashavingCIU80 ofpatientsperceiveitisveryeasytoidentifytheconditionwhenitreappears Norespondentsreporteddifficulty 44 Q Whatwouldyoudoifyouexperiencedothersymptomssuchasdifficultybreathing feverortroubleswallowingwithyourhives 45 PresenceofSeriousSymptoms Lessthan1 95 ofpatientsclaimthattheywouldseekmedicalassistanceifmoreserioussymptomsaroseThisresponseiswithoutthebenefitoflabelingtodirectthem N 388 95 46 Conclusions ConsumerStudy ConsumersconfirmthatrecurrentepisodesofCIUareeasilyrecognizedPhysiciandiagnosedCIUislargelyself managedNearly20 donotreturnforaphysicianvisitTreatmentwithOTCantihistaminespriortophysiciandiagnosisisprevalent 62 Consumersknowtoseekmedicalattentionifserioussymptomsoccur 47 PhysicianPracticesStudyDesign PhysicianScreeningInternetpanelofphysicianscombinedwithapoolofphysiciansfromMedscapeandePocratestotaling200 000PoolofphysiciansscreenedastospecialtyandtreatmentofCIUpatientOncequalified moredetailedsurveyconducted 48 PhysicianPracticesStudyDesign StudyPopulationRandomsampledrawnwasrepresentativeofandprojectabletooffice basedpracticingphysicianswithwebaccess 96 inthespecialtiesstudiedTotalof359interviewsPCP s Dermatologists Allergists Pediatricians 49 Q Whatterminologydoyoutypicallyusewhenexplainingtheinitialdiagnosistoyourpatients 50 NomenclatureUsedToDescribeCIU N 359 Nearlythree fourthsofphysiciansuseeither chronic or recurring hivesindescribingCIUtotheirpatients 51 Q Afterreceivingadiagnosisofchronicidiopathicurticariafromaphysician howlikelydoyoufeelasuffererisabletoself identifyorrecognizerecurrentepisodesofthiscondition 52 LikelihoodofRecognizingRecurrentEpisodes PerceivedLikelihoodtoIdentifyRecurrentEpisodes AfterPhysicianDiagnosis N 359 Very SomewhatLikely96 VeryLikely60 SomewhatLikely36 96 ofphysiciansfeelthatitislikelythatapreviouslydiagnosedCIUpatientcanself recognizerecurrentepisodes 53 Q Thinkingofallthepatientsyouhavecounseledforchronicidiopathicurticariawhatpercentagedoyourecommendkeepmedicineonhandinanticipationofarecurrentepisode 54 PhysicianEncouragedSelf ManagementPractices Virtuallyall 97 physicianscounselsomeCIUpatientstokeepmedicationsonhandincaseofanoutbreakofhivesJustunder60 ofphysicianscounselALLoftheirCIUpatientstokeepmedicationsonhand 55 Conclusions PhysicianPracticesStudy PhysiciansdemonstrateconsensusinthenomenclaturetheyusetodescribeCIUtopatients Chronichives recurrenthives 96 ofphysiciansbelieveitislikelythatpatientscanself recognizerecurrentoutbreaksConfirmslearningofotherstudiesPhysicianprescribing recommendationbehaviorencourageCIUpatientself management 56 SelfRecognitionStudy StudyDesign Allcomers studytodetermineifconsumersthathavebeendiagnosedbyaphysicianashavingrecurrentorchronichivesofanunknownorigincanaccuratelyself recognizetheconditionandsymptomsuponrecurrenceStudyPopulationSubjectswithphysiciandiagnosedCIU N 196 StudyMethodCIUpatientsrecruitedfrom21regionallydispersedcitiesviaradio newspaperadvertisingRequiredtobringthenameandtelephonenumberofthediagnosingphysicianwiththem 57 SelfRecognitionStudy StudyMethod Cont d CIUSubjects MedicalhistorytakenalongwithphotographoflesionsifsufferingPatientswhowerenotsufferingreviewedalternativetextbookphotosoflesionsandselectedonewhichlooksmostliketheirsMaterialssentto reviewedbyphysician TeleconferencewithpatientPhysiciananddermatologistreviewedallinformationtodetermineifsubjecthadaccuratelyself recognizedCIU 58 ConfirmedSelf Recognition NearlyallofthesubjectswhoreportedhavingCIUwereconfirmedbytheinvestigatingphysiciananddermatologistashavingCIU AgreementBetweenPatientAndPhysician 94 59 Conclusions Self RecognitionStudy PreviouslydiagnosedCIUpatientscanaccuratelyself recognizethesymptomsandconditionuponrecurrenceThisisconsistentwiththefindingsofboththeConsumerandPhysicianstudies 60 LabelComprehensionStudy StudyDesign Allcomers studytounderstandtheconsumer sabilitytocomprehendspecificcommunicationspointsonthedraftlabelStudyPopulation N 565 CIUSufferers N 196 GeneralPopulation N 116 LowLiterate N 96 Askadoctorfirst Subjectsthatwereeitherpregnant nursing breastfeedingorhadliverorkidneydisease N 114 AcuteHivesSufferers N 102 61 LabelComprehensionStudy StudyMethodCIUcohortrecruitedviaadvertisingOthercohortsrecruitedviamallinterceptsandspeciallocationsfortheenrichedpopulationsLabelcomprehensionwasassessedbyaskingbothdirectandscenario basedquestionsSelf selectionwasassessedbyposingaquestiontodetermineifconsumersunderstoodtheycouldpersonallyuseClaritin 62 LabelComprehensionStudy FindingsThroughreactionstoscenarios consumersacrossallcohortsdemonstratedastrongunderstanding Thatthisproductshouldnotbeusedinsituationswhereserioussymptomsarepresent GeneralWarnings 75 96 Correct AcceptableResponses OfwhocanandcannotuseClaritin 75 99 Correct Acceptable Ofconditionsunderwhichonemustaskadoctorbeforeuse 94 100 Correct Acceptable Ofconditionsunderwhichtheproductshouldbeused 95 100 Correct Acceptable 63 LabelComprehensionStudy FindingsResponsestoscenariosandquestionsamongthetargetcohortofCIUsuffererswasparticularlystrong 91 99 Correct Acceptable CIUpatientsalsodemonstratedappropriateself selectionforpersonaluse 100 64 LabelComprehension FindingsAmajorityofacutehivessufferers 54 correctlyde selectedtheproductforpersonaluseWhenpresentedwithadirectscenarioofacutehives 75 ofthiscohortcorrectlycomprehendedthattheproductshouldnotbeusedThislevelofcorrectself selectionleadsustofeelpositivethatwecanoptimizelabeling 65 LabelComprehension Correct Acceptable Incorrect Asignificantmajorityofthegeneralpopulationdemonstratesappropriateself selection N 116 PercentofGeneralPopulation 66 Conclusions LabelComprehensionStudy Reactiontothescenariosacrossallcohortsdemonstratesunderstandingofthegeneralwarnings situationsinwhichClaritin should shouldnotbeusedanddirectionsforuseResultsoftheself selection personalusequestionrevealthatamajorityofthegeneralpopulationcanappropriatelyself selecttheproductforuse 67 Conclusions LabelComprehensionStudy Overhalfoftheacutehivesstudysubjectsappropriatelyde selectedtheproductinthepersonalusequestionandscenarioresponsesdemonstratethatthispopulationunderstandsthewarnings NotablythisresultwasachievedwithdraftlabelingthatrequiresrefinementWearecommittedtoworkwithFDAtorefinethelabelingtoimprovecomprehensionamongtheseconsumersBasedonself selectionandresponsetoscenarios consumerswithaphysiciandiagnosisofCIUunderstandthatthisproductisforthemandarelikelytouseitcorrectly 68 Risk BenefitofClaritin OTC FDAanalysisofsafetyofClaritinincludingCIUexperiencesupportssafetyforOTCWorldwidemarketingexperienceasanRxandOTCproductsupportsswitch 69 Claritin MarketingHistory LaunchedinBelgiumin1988 ARandCIU Approvedin114countriesApprovedOTCin33countriesApprovedOTCinCanadain1990for SkinItching Urticaria ApprovedOTCinU K in1993for Hives Urticaria ApprovedRxinU S in1995for CIU 70 Claritin PatientExposure Approximately14billionpatientdaysHalfwithintheU S 457millioncoursesoftreatment 71 Claritin Safety Excellentsafetyprofile 2AEreportsper100 000coursesoftreatment SeriousadverseeventreportsarerareNotadrugofabuseAdverseeventsinCIUaresimilarbetweenOTCandRx 72 PoisonCenterDataonLoratadine NonewsignalsNonewmedicalissuesToxicExposureSurveillanceSystemDatabase1997 2001 73 Claritin OTCExamplesofLabeledIndications Australia chronicurticaria hives itchyrash Canada allergicskinconditions hives Germany chronicurticaria hives withitching Switzerland chronichives urticaria UnitedKingdom allergicskinconditions rash itching andurticaria hives 74 OTCMarketingExperienceCanadaandUnitedKingdom OverallsafetyexperienceOTCissimilartoprescriptionexperienceOTCexperienceingeneralskinallergy urticaria CIUissimilartorhinitisexperienceBasedontotalof38millionpatientdaysofexposure Indications Hives rash allergicskinconditions allergicdermatologicconditions 75 Claritin Safety Conclusion ClinicaltrialandextensiveworldwidemarketingexperiencedocumentanextremelysafeprofileforClaritinforCIUClaritinOTChasasafeprofileworldwideinanOTCsetting 76 CurrentpracticesandstandardsofcaresupportCIUasOTCindicationMultiplerefillsOTCmedicationsLimitedphysicianoversightConsumerscurrentlyself treatwithsedatingOTCantihistaminesforall