文档介绍：Tysabri®(natalizumab) BiogenIdecInc. BLA125104/mitteeGaithersburg,MarylandMarch7-8,2006AliceHughes,-PMLSafetyIssues2OutlineInfectionsotherthanPMLImmunogenicityandhypersensitivityreactionsCarcinogenicityPost-marketingreportsofseriousadverseeventsSummaryofmajorsafetyconcerns3Natalizumab-andplacebo-treatedpatientshadsimilarincidencesof:infectionsoverall:%%()seriousinfections:%%Natalizumab-andplacebo-treatedpatientshadsimilarincidencesof:upperrespiratorytractinfections:%%UTIs:%%seriousUTIs:%%gastroenteritis:%%InfectionsotherthanPML: Placebo-controlledMSstudies4InfectionsotherthanPML: MSstudiesIncidencesofspecificinfectionsinplacebo-controlledstudies:alllowerrespiratorytractinfections:%%()seriouspneumonias:%%vaginalinfections:%%allherpesinfections:%%gingivalinfections:%%Atypicalinfectionscryptosporidialgastroenteritiswithprolongedcourse(inmonotherapyStudy1801)acuteCMVinfectionwithtransaminitis(inopen-labelStudy1808)5InfectionsotherthanPML: Placebo-controlledCDstudiesIncidenceofinfectionsoverall:%%()Incidenceofseriousinfections:%%Incidencesofselectedinfections:URIs:27%%UTIs:%%vaginalinfections:%%allherpesinfections:%%perianalabcesses:%%seriousviralmeningitides:%(2):%(2)(CMVcolitis)Patientalsoreceivingazathioprine6InfectionsotherthanPML: Long-itantimmunosuppressive/immunomodulatoryagentsandintercurrentillnesses7ImmunogenicityAnti-natalizumabantibodyformationassessedevery12weeksinPhase3MSStudiesandselectedCDstudies10%ofpatientshadapositiveantibodytiteratleastonce4%ofpatientsweretransientlypositiveand6%werepersistentlypositiveinMSStudiesIncidenceofanti-natalizumabantibodyformationwashigherinStudy1802(12%)thanin1801(9%)Intermit