吡格列酮與膀胱癌的部分相關(guān)資料

1/1吡格列酮與膀胱癌的部分相關(guān)資料新聞稿：

FDA:UseofpioglitazoneoveroneyearmayincreaseriskofbladdercancerJUNE15,2011|ShelleyWoodSilverSpring,MD-TheFDAhasissuedanupdatetoitsongoingsafetyreviewofpioglitazone(Actos,Takeda),informingphysiciansandthepublicthatuseofthedrugformorethan12monthsislinkedtoanincreasedriskofbladdercancer[1].ThenewscomeswithindaysofFrenchregulatorsannouncingthattheyaresuspendingsalesofthedrug;Germanregulatorsalsoannouncedlastweekthatpioglitazoneshouldnotbestartedinnewpatients.IntheFDA’sannouncementtoday,theagencystatedthatinformationonthedrug’slabel,aswellasthepatientmedicationguide,willberevisedtoincludethisnewinformation.Specifically,saystheFDA,physiciansshould:Notusepioglitazoneinpatientswithactivebladdercancer.Usepioglitazonewithcautioninpatientswhohaveapriorhistoryofbladdercancer,addingthebenefitsofbloodsugarcontrolwithpioglitazoneshouldbeweighedagainsttheunknownrisksforcancerrecurrence.Tellpatientstoreportanysignsorsymptomsofbloodintheurine,urinaryurgency,painonurination,orbackorabdominalpain,asthesemaybeduetobladdercancer.Urgepatientstoreadthepioglitazonemedicationguide.ReportadverseeventsinvolvingpioglitazonemedicinestotheFDAMedWatchprogram.Aspreviouslyreportedbyheartwire,theFDAhasbeenreviewingthesafetyofpioglitazonesinceSeptember2010,citingpreliminaryepidemiologicalevidencethatsuggeststhatthediabetesmedicationmaybelinkedtoahigherriskofbladdercancer.Justlastweek,anFDAspokespersonpredictedthattheagency’sreviewwouldbecompletewithinthenextcoupleofmonths.Ofnote,theFDAannouncementtodayreferstothereviewasongoing.TheFDA’sannouncementtodayincludesanupdateonthedatausedtomaketherecommendationsandnotesthattheFDAwasawareoftheFrenchanalysisthatledtotheactiontakeninthatcountry.TheFDAreviewisbasedonanongoing10-yearobservationalcohortstudyaswellasanested,case-controlstudyofthelong-termriskofbladdercancerinover193000patientswithdiabeteswhoaremembersoftheKaiserPermanenteNorthernCalifornia(KPNC)healthplan.TheFDAtodayspecifiedthatcomparedwithneverbeingexposedtopioglitazone,adurationofpioglitazonetherapylongerthan12monthswasassociatedwitha40%increaseinriskintheKPNCanalysisandthataftermorethan24monthsofpioglitazoneusethatincreasedriskremained,althoughthestatisticalsignificanceofthefindingwasweaker.Basedonthesedata,FDAcalculatedthatdurationoftherapylongerthan12monthswasassociatedwith27.5excesscasesofbladdercancerper100000person-yearsfollow-up,comparedwithneveruseofpioglitazone,today’snoticereads.AdditionaldetailsontheFDA’sdatareviewareincludedintheannouncement.AccordingtotheFDA,approximately2.3millionpatientsfilledaprescriptionforapioglitazone-containingproductfromoutpatientretailpharmaciesintheUSfromJanuary2010throughOctober2010.Frenchregulatorssuspendpioglitazone,citingcancerriskJUNE9,2011|ShelleyWoodParis,France-TheFrenchdrugregulatoryauthority,theFrenchAgencyfortheSafetyofHealthProducts(AFSSAPS),hassuspendedthemarketingofpioglitazone(Actos,Takeda),followingtherecommendationofitsCommissiond’AutorisationdeMisesurleMarch(AMM)andNationalCommissiononPharmacovigilance[1].ThedecisionwasmadeafterastudyrequestedbyAFSSAPSconfirmedasmallincreaseinbladdercanceramongpatientstreatedwiththediabetesdrug.Fornow,AFSSAPSisrecommendingthatpatientstakingpioglitazonenotstoptheirtreatmentbutconsultwiththeirdoctorstohavetheirtreatmentadjusted.Physiciansshouldnot,however,prescribeanymoredrugscontainingpioglitazone,theAFSSAPSstatementnotes.AFSSAPShadsentaletterApril19tophysiciansalertingthemofthepotentialcancerrisk.AsubsequentreviewofpharmacovigilancedatapresentedtothecommissioninrecentmonthshadledtheAMMtoconcludethattherisksassociatedwithpioglitazoneuseexceeditsbenefits.FrenchphysicianswillreceiveanewletterinthenextfewdayswithdetailsontheAFSSAPSdecision.ReportingontheFrenchannouncementearliertoday,BloombergnewsservicenotedthattheEuropeanMedicinesAgency,whichannouncedareviewofpioglitazoneinMarch,planstodiscussthesafetyofpioglitazoneatitsnextmeeting,theweekofJune20,buthasmadenorecommendationsonthedrugwhileadecisionispending.Aspreviouslyreportedbyheartwire,theFDAisalsointheprocessofreviewingthesafetyofpioglitazone,citingpreliminaryepidemiologicalevidencethatsuggeststhatthediabetesmedicationmaybelinkedtoahigherriskofbladdercancer.AnFDAspokespersontoldheartwiretodaythattheFDAiscontinuingtoreviewthedataandwillmakeadeterminationonwhatregulatoryactionsarenecessaryonceitsreviewiscomplete.Weanticipatethisreviewtobecompletewithinthenextcoupleofmonths.TheFDAreviewisbasedonanongoing10-yearobservationalcohortstudyaswellasanested,case-controlstudyofthelong-termriskofbladdercancerinroughly193000patientswithdiabeteswhoaremembersoftheKaiserPermanenteNorthernCaliforniahealthplan.Apreliminaryanalysisofthesedatashowedanincreasingriskofbladdercancerwithpioglitazoneexposure,ariskthatreachedstatisticalsignificanceafter24months.Justlastmonth,anewanalysisusingtheFDAadverse-eventreportingsystem(AERS)foundasignificantincreaseinbladdercanceramongdiabeticpatientstakingpioglitazone.PioglitazonehasbeenmarketedinFrancebothonitsown(Actos)since2000andincombinationwithmetformin(Competact)since2006.Theagencyestimatesthat230000patientsinFrancearecurrentlytakingpioglitazoneinsomeform.FDAprobingpossiblepioglitazone,bladder-cancerlinkSEPTEMBER17,2010|RobertLowesSilverSpring,MD-TheUSFoodandDrugAdministration(FDA)isreviewingthesafetyofpioglitazone(Actos,TakedaPharmaceuticals),citingpreliminaryepidemiologicalevidencethatsuggeststhatthediabetesmedicationmaybelinkedtoahigherriskofbladdercancer,theagencysaidFriday.Aswithotherannouncementsaboutdrugsunderpostmarketscrutiny,theagencynotedthatithasnotyetconcludedthatpioglitazoneincreasestheriskofbladdercancerandurgedpatientstakingthemedicationtocontinuetodosounlesstoldotherwisebytheirhealthcareprofessional.Pioglitazonewasapprovedin1999andisoneoftwoFDA-approvedmedicationsinthethiazolidinedione(TZD)classalongwithrosiglitazone(Avandia,GlaxoSmithKline),itselfthesubjectofanongoingandcontroversialsafetyreview.Theagencyisstilldeliberatingwhethertotakerosiglitazoneoffthemarketoraddstricterrestrictionsandlabelwarningsaboutitscardiovascularrisks,followingamixedvotebyajointFDAadvisorypanelmeetinginJuly.PioglitazonegenerallyhasbeenviewedasasaferoptionforpatientswhowarranttreatmentwithaTZD-classdrug:duringtherosiglitazoneadvisoryhearing,mostpanelmemberssaidtheybelievedpioglitazonetobesaferthanrosiglitazone.Thecancersignalwithpioglitazone,however,wasdiscussedduringtherosiglitazonemeetingandclearlycausedconsternationamongsomeofthepanelmembers.AccordingtoanFDAstatement,itsannouncementFridayaboutpioglitazoneisbasedonanon-going10-yearobservationalcohortstudyaswellasanested,case-controlstudyofthelong-termriskofbladdercancerinroughly193000patientswithdiabeteswhoaremembersoftheKaiserPermanenteNorthernCaliforniahealthplan.AninterimanalysisofdatacollectedfromJanuary1,1997throughApril20,2008didnotshowastatisticallysignificantassociationbetweenanyexposuretopioglitazoneandanincreasedriskofbladdercancer.However,thisriskdidincreaseinpatientsexposedtothehighestcumulativedoseandthosewiththelongestexposure,reachingstatisticalsignificanceaftertwoyears.Thefirstsuggestionofapossiblecancerriskemergedinpreclinicalcarcinogenicitystudiesdescribedinthedrug’sFDA-approvedlabel.Bladdertumorswereseeninmaleratsreceivingadoseofpioglitazonethatproducedblooddruglevelsequivalenttowhataclinicaldosewouldgenerate.Andintwoclinicalstudies,patientsreceivingpioglitazoneexperiencedahigherrateofbladdercancerthanpatientstakingotheragents.Moreinformationabouttoday’sFDAannouncementisavailableontheagency’swebsite.新近研究CohortStudyofPioglitazoneandCancerIncidenceinPatientsWithDiabetesDiabetesCareApril201134:923-929;doi:10.2337/dc10-10671.AssiamiraFerrara,MD,PHD1,2.JamesD.Lewis,MD,MSCE2,3,4,5,3.CharlesP.QuesenberryJr.,PHD1,4.TiffanyPeng,MA1,5.BrianL.Strom,MD,MPH2,3,4,5,6.StephenK.VanDenEeden,PHD1,7.SamanthaF.Ehrlich,MPH1and8.LaurelA.Habel,PHD1+AuthorAffiliations1.1DivisionofResearch,KaiserPermanenteNorthernCalifornia,Oakland,California2.2CenterforClinicalEpidemiologyandBiostatistics,UniversityofPennsylvania,Philadelphia,Pennsylvania3.3CenterforEducationandResearchinTherapeutics,UniversityofPennsylvania,Philadelphia,Pennsylvania4.4DepartmentofBiostatisticsandEpidemiology,UniversityofPennsylvania,Philadelphia,Pennsylvania5.5DepartmentofMedicine,UniversityofPennsylvania,SchoolofMedicine,Philadelphia,Pennsylvania1.Correspondingauthor:AssiamiraFerrara,assiamira.ferrara@.AbstractOBJECTIVEToexplorewhethertreatmentwithpioglitazonewasassociatedwithriskofincidentcanceratthe10mostcommonsites(prostate,femalebreast,lung/bronchus,endometrial,colon,non-Hodgkinlymphoma[NHL],pancreas,kidney/renalpelvis,rectal,andmelanoma).RESEARCHDESIGNANDMETHODSAcohortstudyof252,467patientsaged40yearsfromtheKaiserPermanenteNorthernCaliforniaDiabetesRegistrywasconducted.Allprescriptionsfordiabetesmedicationswereidentifiedbypharmacyrecords.Coxproportionalhazardsmodelswereusedtoexaminetheassociationbetweenriskofincidentcancerandeveruse,duration,dose,andtimesinceinitiationofpioglitazone(modeledastime-dependentvariables).RESULTSInmodelsadjustedforage,sex,yearofcohortentry,race/ethnicity,income,smoking,glycemiccontrol,diabetesduration,creatininelevels,congestiveheartfailure,anduseofotherdiabetesmedications,thehazardratio(HR)foreachcancerassociatedwitheveruseofpioglitazonerangedfrom0.7to1.3,withall95%CIsincluding1.0.Therewasasuggestionofanincreasedriskofmelanoma(HR1.3[95%CI0.92.0])andNHL(1.3[1.01.8])andadecreasedriskofkidney/renalpelviscancers(0.7[0.41.1])associatedwitheveruseofpioglitazone.Theseassociationswereunalteredwithincreasingdose,duration,ortimesincefirstuse.CONCLUSIONSWefoundnoclearevidenceofanassociationbetweenuseofpioglitazoneandriskoftheincidentcancersexamined.Becausethemaximumdurationoffollow-upwasfewerthan6yearsaftertheinitiationofpioglitazone,longer-termstudiesareneeded.RiskofBladderCancerAmongDiabeticPatientsTreatedWithPioglitazoneInterimreportofalongitudinalcohortstudyDiabetesCareApril2011vol.34no.4916-9221.JamesD.Lewis,MD,MSCE1,2,3,2.AssiamiraFerrara,MD,PHD4,3.TiffanyPeng,MA4,4.MoniqueHedderson,PHD4,5.WarrenB.Bilker,PHD1,2,6.CharlesP.QuesenberryJr.,PHD4,7.DavidJ.Vaughn,MD3,8.LisaNessel,MSS,MLSP1,9.JosephSelby,MD4and10.BrianL.Strom,MD,MPH1,2,5+AuthorAffiliations1.1CenterforClinicalEpidemiologyandBiostatistics,UniversityofPennsylvania,Philadelphia,Pennsylvania2.2DepartmentofBiostatisticsandEpidemiology,UniversityofPennsylvania,Philadelphia,Pennsylvania3.3DepartmentofMedicine,UniversityofPennsylvania,Philadelphia,Pennsylvania4.4DivisionofResearch,KaiserPermanenteNorthernCalifornia,Oakland,California5.5DepartmentofPharmacology,UniversityofPennsylvania,Philadelphia,Pennsylvania1.Correspondingauthor:JamesD.Lewis,lewisjd@.AbstractOBJECTIVESomepreclinicalinvivostudiesandlimitedhumandatasuggestapossibleincreasedriskofbladdercancerwithpioglitazonetherapy.Thisisaninterimreportofanongoingcohortstudyexaminingtheassociationbetweenpioglitazonetherapyandtheriskofbladdercancerinpatientswithdiabetes.RESEARCHDESIGNANDMETHODSThisstudyincludes193,099patientsintheKaiserPermanenteNorthernCaliforniadiabetesregistrywhowere40yearsofagebetween1997and2002.Thosewithpriorbladdercancerwereexcluded.Everuseofeachdiabetesmedication(definedastwoormoreprescriptionswithin6months)wastreatedasatime-dependentvariable.Coxregressiongeneratedhazardratios(HRs)comparedpioglitazoneusewithnonpioglitazoneuseadjustedforage,sex,race/ethnicity,diabetesmedications,A1C,heartfailure,householdincome,renalfunction,otherbladderconditions,andsmoking.RESULTSThegrouptreatedwithpioglitazonecomprised30,173patients.Therewere90casesofbladdercanceramongpioglitazoneusersand791casesofbladdercanceramongnonpioglitazoneusers.Overall,everuseofpioglitazonewasnotassociatedwithriskofbladdercancer(HR1.2[95%CI0.91.5]),withsimilarresultsinmenandwomen(testforinteractionP=0.8).However,intheaprioricategoryof24monthsoftherapy,therewasanincreasedrisk(1.4[1.032.0]).Ninety-fivepercentofcancersdiagnosedamongpioglitazoneusersweredetectedatearlystage.CONCLUSIONSInthiscohortofpatientswithdiabetes,short-termuseofpioglitazonewasnotassociatedwithanincreasedincidenceofbladdercancer,butuseformorethan2yearswasweaklyassociatedwithincreasedrisk.AssessingtheAssociationofPioglitazoneUseandBladderCancerThroughDrugAdv