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switch(OR 1.6;1.2-2.1)anddiscontinuation(OR 1.8;1.5-2.1).Heartfailurewasassociatedwithaugmentation(OR 1.6;1.0-2.5)anddiscontinuation(OR 1.7;1.2-2.4).Agewas inverselyassociatedwithaugmentationanddiscontinuationandtimesincediabetesdiagnosiswasalsoinverselyassociatedwithaugmentation. CONCLUSIONS: HbA1cisa cleardriveroftreatmentregimenchangesalthoughthereareotherfactorsalso independentlyrelatedtochangesuchasage,heartfailureandbaselineOAD. PDB79 TREATMENTPATTERNSOFORALANTI-DIABETICDRUGSINTHEUKMaguireA1,MitchellB2 1UnitedBioSourceCorporation,London,UK,2EliLillyandCompany,Indianapolis,IN,USAOBJECTIVES: IntheUK,OralAnti-DiabeticdrugsOADareadministeredtocontrol hyperglycaemiaintype2diabeteswhenHbA1cexceeds48mmol/mol.Treatment guidelinesdetermineinitialOADandsubsequentchangesinregimendependon HbA1cresponse.Hence,theaimofthisstudyistoquantifyOADtreatment patterns. METHODS: AllpatientswhoinitiatedanOAD(exceptrosiglitazone)with rstuseasindexdate,intheGPRDdatabasebetween1/1/2006and25/2/2011were included.Periodsofcontinuousandoverlappingprescribing(Rx)wereusedto denediscontinuation,switchingandaugmentation;agapof60dayssinceexpiry ofRxdeneddiscontinuation. RESULTS: Of63060patientscommencingOAD,88% startedonmetforminand8%ongliclazidebothasmonotherapy.Hence,allother OADregimenscomprisedonly4%ofallpatients.Comparedtometformin,the gliclazidepatientgroupwasolder(meanage67vs.61years)andhadhighermedianbaselineHbA1c(70(IQR60-95)vs.64(IQR56-74)mmol/mol).TherateofdiscontinuationofbaselineOADatoneyearwas32%whilstthediscontinuationofall OADwas26%.ItwasrarefordiscontinuationofOADtobepermanent;only3.3%of patientswhodiscontinuedinthe1st12monthsdidnotrestartduring4years.The rateofswitchingwas6.4%andtherateofaugmentationwas15%overtherstyear. TheseratesdifferedaccordingtobaselineOAD.Comparedtometforminthediscontinuationrateofgliclazidewashigher(41%vs.30%),aswasswitching(8.4%vs. 6.1%)andaugmentation(23%vs.14%).Lastly,insulinuptakewasjust2%byone yearsinceOADinitiation;againthiswashigherinthegliclazidegroupcomparedto metformin(7%vs.1.4%). CONCLUSIONS: Mostpatientsinitiatedonmetformin, whilstforthoseinitiatingongliclazide,discontinuation,switching,augmentation andinsulininitiationwereallhigher.MostpatientswhodiscontinuedOADsubsequentlyrestarted. SYSTEMICDISORDERS/CONDITIONS-ClinicalOutcomesStudies PSY1 CARDIOVASCULARANDCONGENITALSAFETYEVALUATIONOFANTIOBESITY AGENTS,INCLUDINGTOPIRAMATE:APHARMACOVIGILANCEANALYSISOF THEADVERSEEVENTREPORTINGSYSTEMAliAK UniversityofFlorida,Gainesville,FL,USAOBJECTIVES: Amyriadofpharmacologicagentsaredevelopedinattemptstocontrolobesity,includingtheextensionoftheantiepileptictopiramateasanantiobesityagent.However,concernsaboutthesafetyofsuchagentsaremounting.This studyaimedatevaluatingthecardiovascularandcongenital(CC)safetyofmarketedantiobesityagents,includingtopiramate. METHODS: Apharmacovigilance analysisofadverseeventreportsspontaneouslysubmittedtotheUSFoodand DrugAdministrationsAdverseEventReportingSystem(AERS)from2004to2011 wasconducted.TheProportionalReportingRatio(PRR)dataminingalgorithmis usedtodetectsignalsofCCadverseeventsthatarereportedfororlistat,phentermine,sibutramine,andtopiramate.SafetysignalsaredetectedforPRRvalues 2. ThevaluesarecomparedwithinantiobesityclassandtoalldrugsinAERS. RESULTS: Atotalof41,930adverseeventreportsforantiobesityagentsweresubmittedtotheAERSduringthestudyperiod.About4%and1%ofthereportswerefor cardiovascularandcongenitalproblems,respectively.Comparedtoalldrugsin AERS,antiobesityagentsdidntshowhigherthanexpectedreportingofcardiovascularevents(PRR0.71,95%CI0.68-0.74).However,theyshowedsignicantsafety signalsregardingcongenitalanomalies(PRR7.45,95%CI6.82-8.0),whichwere mostlyattributedbytopiramate.Comparedtootherantiobesityagents,sibutraminewasassociatedwithhighercardiovascularreportingrates(PRR4.42,95%CI 4.0-4.85),e.g.cardiacarrhythmias,pulmonaryhypertension,hypertension,coronaryarterydisease,andstroke.Phenterminewasassociatedwithvalvularheart disease(VHD),pulmonaryhypertension,andstroke.Topiramatewasassociated withcongenitalanomaliesandVHD. CONCLUSIONS: Antiobesityagentsshouldbe prescribedwithcautiontopatientswithcardiovascularriskfactors.Regulatory authoritiesshoulddenecardiovascularsafetysurveillancerequirementsforantiobesityagentsatpostmarketingstagesofproductslifecycle.Analternativeto topiramateshouldbeprescribedtofemalesofchildbearingage.Epidemiological studiesarewarrantedtotestthegeneratedhypotheses. PSY2 PRELIMINARYVALIDATIONOFCOLLECTSCALE:ACO-MORBIDITY ASSESSMENTTOOLFORPATIENTSWITHCHRONICLYMPHOCYTICLEUKAEMIAGiraldoP1,LopezA2,RiosE3,Gonzalez-GrandeI4,RosetM5,Castro-GomezA6,DeLa SernaJ7,CarbonellF8 1HospitalUniversitarioMiguelServet,Zaragoza,Spain,2HospitalUniversitariValledHebron, Barcelona,Spain,3HospitalVirgendeValme,Sevilla,Spain,4RocheFarma,S.A.,Madrid,Spain,5IMSHealth,Barcelona,Spain,6Roche,Madrid,Spain,7HospitalUniversitario12deOctubre, Madrid,Spain,8ConsorciHospitalGeneralUniversitariValencia,Valencia,SpainOBJECTIVES: COLLECTscalewasdevelopedtoassessthelevelofcomorbiditywith animpactontreatmentdecisionforpatientswithChronicLymphocyticLeukaemia(CLL)in5steps:1.-Literaturereview,2.-FocusGroup,3.-Pilotstudytoevaluate scalefeasibility,4.-Scaledesign,5.-Scalevalidationinanobservational,prospectivephaseIVstudy(evaluatingsafetyproleofRituximabinCLL).ThiscommunicationpresentsthepreliminaryvalidationoftheCOLLECTscale. METHODS: Atotal of219patientswereincluded.ThescaleistobefullledbeforeinitiatingCLL treatmentanditcollatesandratesthepresenceof11relevantcomorbidities.The rangeofthescoregoesfrom0to57points.Fourscoringclusterswerepredened: 0-3points(lowcomorbidity),4-6(mildcomorbidity),7-10(moderatecomorbidity) and 10(highcomorbidity). RESULTS: Datafrom218patientsof47hospitalswere analyzed.MostfrequenttherapeuticschemewasRituximab-Fludarabine-Cyclophosphamide(R-FC)(41.3%),followedbyRituximab-Bendamustine(R-B)(29.6%) andRituximab-Chlorambucil(R-Cl)orschemesincludingalkylatingagents(21.1%). COLLECTmedianscore(SD)was4(0-21)withameanof4.8(3.1)points.39.2%of patientsscoredbetween4-6and33%between0-3.StatisticallysignicantdifferenceswereobservedinCOLLECTscoreaccordingtoage(p 0.01)andEGOG (p 0.01):thegreatertheageandECOG,thegreaterthescore.Theelectionofinmunochemotherapytreatmentdiffereddependingonthescorecluster(p 0.002): 50.6%and32,9%ofpatientstreatedwithR-FChadlowandmildcomorbiditylevel respectively.40,0%ofpatientsreceivingR-Bhadmediumand26.5%highcomorbiditylevel.50%ofpatientstreatedwithR-Clscoredbetween4-6andthe23.5% between7-10. CONCLUSIONS: COLLECTscaleallowsdening4levelsofcomorbidities,withaverygoodcorrelationtoageandECOGstatus.Althoughtheaimof thescaleisnottodrivetreatmentdecision,thestudyshowsatrendtoassociate comorbidityscorewithintensityoftreatment. PSY3 DISEASEACTIVITYINDICES(DAIS)INSYSTEMICLUPUSERYTHEMATOSUS (SLE)WyrwichK1,WinnetteR2,OglesbyA3,NarayananS4 1UnitedBioSourceCorporation,Bethesda,MD,USA,2UnitedBioSourceCorporation,London,UK,3GlaxoSmithKline,ResearchTrianglePark,NC,USA,4HumanGenomeSciences,Inc.,Rockville, MD,USAOBJECTIVES: Reviewthedevelopmentandpropertiesofsystemiclupuserythematosus(SLE)diseaseactivityindices(DAIs)usedinclinicaltrials,observational studies,andcasestudies. METHODS: Astructuredsearchwasconductedtoidentifypublishedarticlesin2005-2011throughkeyliteraturedatabases(EMBASEand MEDLINE/PUBMED).Conferenceabstractsfromtargetedrheumatology,outcomes researchandquality-of-lifescienticmeetingsin2009-2011wereincluded.SLE therapyclinicaltrialswithinthepastveyearswereidentiedthroughtheClinicalTrials.govdatabase. RESULTS: Thesearchresultedinmorethan15different DAIs,withthemostfrequentlyusedbeingtheBritishIslesLupusAssessment GroupScale(BILAG),EuropeanConsensusLupusActivityMeasure(ECLAM),SystemicLupusActivityMeasure(SLAM),SLAM-revised(SLAM-R),SystemicLupus ErythematosusDiseaseActivityIndex(SLEDAI),SLEDAI-2K,SafetyofEstrogenin LupusErythematosusNational-SLEDAI(SELENA-SLEDAI),andSLEDAI-2K-50(SRI50).Thenumberofitems(24-97),timetocomplete(5-20mins; 20minsforsome toolsincaseoflessphysiciantraining/familiarity),scoring(noglobalscoreor 0-105),organ/systemsassessed(8-24),andsubscalesobservedinthesemeasures variedwidely.TheseeightDAIsalldemonstratedsubstantialinter-raterreliability (ICC .61-1.0)andhadmoderatetostrongcorrelationswitheachother(r 0.430.97).MeasuresinallbutBILAGwereweighted.Allofthesetoolsrequireperiodic laboratoryassessmentssuchashemoglobin,whitecellcount,complementlevels, orincreasedDNAbinding.Abilitytodiscriminatebetween-patientandbetweenvisitdifferencesvariedacrossthetools. CONCLUSIONS: BILAGandSELENA-SLEDAIorinstrumentsderivedfromthesetoolsareusedwidelyinSLEclinicalresearch.However,giventhecomplexity,cliniciantimerequiredforaccurate completion,andneedforlabassessmentstocompletethesetools,furtherinvestigationisneededtoassesstheirfeasibilityforuseoutsideoftheresearcharenain routineclinicalpracticeforoptimalSLEmanagement. PSY4 LENALIDOMIDEORBORTEZOMIBFORTHETREATMENTOF RELAPSED/REFRACTORYMULTIPLEMYELOMA(MM):ACOMPARATIVE EFFECTIVENESSANALYSISUSINGINDIRECTSTATISTICALTECHNIQUESKauraS1,DranitsarisG2 1CelgeneCorporation,Summit,NJ,USA,2AugmentiumPharmaConsulting,Toronto,ON,CanadaOBJECTIVES: Lenalidomide(LEN)andbortezomib(BORT)arebotheffectiveforthe treatmentofrelapsed/refractoryMM.Theformerisadministered25mg/dayorally ondays1-21ofrepeated28-daycycles.Thelatterasa1.3mg/m2intravenousdose ondays1,4,8and11foreight,threeweekcycles.Currently,therearenodatafrom headtoheadrandomizedtrialscomparingLENandBORT.Intheabsenceofsuch data,anindirectcomparisonbetweenLENandBORTwasperformedintherelapsed/refractoryMMsetting.Suchananalysiswasfeasiblebecausecomparable controlswereusedinthepivotalrandomizedtrialsandpatientshadsimilarbaselinecharacteristics. METHODS: ThreepivotalrandomizedtrialswithLEN(n 2) andBORT(n 1)intherelapsed/refractorysettingwereidentied.Patientswithin eachtrialhadsimilardiseasecharacteristics.Dataintermsofresponserate(RR), timetoprogression(TTP)andoverallsurvival(OS)wereextractedfromthepivotal trials.AnindirectstatisticalcomparisonbetweenLENandBORTwasthenperformedontheseendpointsusingthemethodofBucheretal.(1997),whichpartly maintainsthebenetsofrandomizationonthemagnitudeofbenet. RESULTS: Theanalysisidentiedsignicantdifferencesinefcacybetweenthesedrugs.PatientstreatedwithLENweresignicantlymorelikelytoachieveadiseaseresponse (OR 1.92;95%CI:1.15-3.20)andtohaveaprolongationinTTP(HR 0.64;95%CI: 0.44-0.91).TheanalysisalsoidentiedatrendforanOSbenetinpatientsreceivingtreatmentwithLENoverBORT(HR 0.71;95%CI:0.46-1.11). CONCLUSIONS:A508VALUEINHEALTH15(2012)A277
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