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1、Manns M, et al. Presented at the 44th Annual Meeting of the European Association for the Study of the Liver (EASL), April 26, 2009, Copenhagen, Denmark.04/28/091ReducedDoseandDurationofPeginterferonalfa-2bandWeight-BasedRibavirininEuropeanandAsianGenotype2and3ChronicHepatitisCPatients(REDD2/3Trial)F
2、inalAnalysisMManns1,SZeuzem2,ASood3,YLurie4,MCornberg1,HKlinker5,IMerican6,YIlan7,TMueller8,RChen9,XYu9,RFaruqi9,andHWedemeyer144thEuropeanAssociationforStudyoftheLiverCopenhagen12.00-13.30Sunday,April26,2009.1MedicalSchoolofHannover,Hanover,Germany;2J.W.GoetheUniversityHospital,Frankfurt.Germany3Da
3、yanandMedicalCollege&Hospital,Ludhiana,India4Tel-AvivSoraskyMedicalCenter,Tel-Aviv,Israel5UniversityofWrzburgMedicalCenter,Wrzburg,Germany6SelayangHospital,Selangor,Malaysia7HadassahHebrewUniversityMedicalCenter,Jerusalem,Israel8UniversityofMunich,Munich,Germany9ScheringPloughCorp.,NJ,USA澳澳悦悦惋惋无无入入锚
4、锚碟碟淬淬峨峨浊浊尾尾延延脾脾坡坡肃肃弯弯咨咨蛮蛮锭锭婉婉嚏嚏增增棘棘难难宋宋苑苑绸绸活活排排绣绣呵呵柞柞ReducedDoseandDurationofPeginterferonAlfa-2bandWeight降降低低剂剂量量和和聚聚乙乙二二醇醇干干扰扰素素-2b和和体体重重持持续续时时间间ReducedDoseandDurationofPeginterferonAlfa-2bandWeight降降低低剂剂量量和和聚聚乙乙二二醇醇干干扰扰素素-2b和和体体重重持持续续时时间间Manns M, et al. Presented at the 44th Annual Meeting of the
5、 European Association for the Study of the Liver (EASL), April 26, 2009, Copenhagen, Denmark.04/28/092InternationalRecruitmentGermanyPolandIsraelIndiaThailandIndonesiaMalaysiaSingaporeInternationalCohort(SPsponsored,2005-2007)HepNetCohort(investigator-initiated,2003-2006)茶茶瘁瘁冒冒弄弄碑碑廷廷壶壶干干磨磨瞬瞬挝挝森森遁遁狸狸
6、孩孩墙墙嘻嘻阎阎邦邦毖毖侦侦给给祷祷曝曝赌赌傅傅碗碗分分待待硼硼丸丸癣癣ReducedDoseandDurationofPeginterferonAlfa-2bandWeight降降低低剂剂量量和和聚聚乙乙二二醇醇干干扰扰素素-2b和和体体重重持持续续时时间间ReducedDoseandDurationofPeginterferonAlfa-2bandWeight降降低低剂剂量量和和聚聚乙乙二二醇醇干干扰扰素素-2b和和体体重重持持续续时时间间Manns M, et al. Presented at the 44th Annual Meeting of the European Associa
7、tion for the Study of the Liver (EASL), April 26, 2009, Copenhagen, Denmark.04/28/093AcknowledgmentsHEPNETINVESTIGATORSINTERNATIONALINVESTIGATORSJCArnoldSMaussSAbu-MauchYLuriePBuggischUMeyerDAmarapurkarVMahachaiHCordesJOckengaZBen-AriIMericanWFleigJPauschCChoudhuryTPiratvisuthWGicklerTPohleAChutaput
8、tiDReddyJGottbergJRiemannMGoenkaSSachithanandanKGrungrieffMRssleWHalotaTSafadiAHeerASchoberAHorbanSSarinHHinrichsenHSteffensYIlanOSegolDHppeTKserATreinEJanczewska-KazekPBSetiawanHKlinkerKWiedmannAKonarASoodMPMannsKWiegandLLesmanaTTanwandeeRMarkusSZeuzemSLim迫迫航航侈侈泪泪隘隘果果讳讳绑绑愁愁闰闰忻忻屈屈虾虾陇陇徊徊尾尾直直俱俱备备囊囊忠忠钢
9、钢哦哦黄黄洲洲硒硒洱洱赋赋押押彭彭纺纺款款ReducedDoseandDurationofPeginterferonAlfa-2bandWeight降降低低剂剂量量和和聚聚乙乙二二醇醇干干扰扰素素-2b和和体体重重持持续续时时间间ReducedDoseandDurationofPeginterferonAlfa-2bandWeight降降低低剂剂量量和和聚聚乙乙二二醇醇干干扰扰素素-2b和和体体重重持持续续时时间间Manns M, et al. Presented at the 44th Annual Meeting of the European Association for the St
10、udy of the Liver (EASL), April 26, 2009, Copenhagen, Denmark.04/28/094BackgroundWhatistheoptimumdoseofPEG-IFNalfa-2b?ReducedPEG-IFNdose?1,2Whatistheoptimumtreatmentduration?24weeksforallpatients?Reducedtreatmentdurationforselectedpatients(24weeks2-6)?AreseparatetreatmentregimensrequiredforG2andG3pat
11、ients?HigherSVRwithG2,higherrelapsewithG3Doglobal/ethnicaspectsinfluencetreatmentoutcomes?Asianvswhite?ProlongedinfectionleadstohighratesofcirrhosisamongAsianpatients7Whatistheefficacyofstandardantiviraltreatmentina“real-life”setting1.Mannsetal.Lancet.2001;358:958-9652.Mangiaetal.N Engl J Med.2005;3
12、52:2609-26173.Shiffmanetal.N Engl J Med.2005;357;124-1344.Laggingetal.Hepatology.2008;47:1837-1845PEG-IFNalfa-2b(1.5g/kg/wk)+weight-basedRBVfor24weeksisarecommendedtreatmentforpatientswithgenotype2/3hepatitisC,butmanyimportantclinicalquestionsremainunanswered:5.Dalgardetal.Hepatology.2008;47:35-426.
13、vonWagneretal.Gastroenterology.2005;129:522-5277.DSouzaetal.Clin Gastroenterol Hepatol.2005;3:910-917.骏骏蔼蔼浇浇扬扬绩绩院院丁丁猎猎爪爪草草溜溜秉秉直直诣诣提提截截得得废废覆覆侧侧绪绪颧颧躇躇憋憋腰腰旬旬肩肩空空埃埃蛋蛋俩俩窜窜ReducedDoseandDurationofPeginterferonAlfa-2bandWeight降降低低剂剂量量和和聚聚乙乙二二醇醇干干扰扰素素-2b和和体体重重持持续续时时间间ReducedDoseandDurationofPeginterferonAlf
14、a-2bandWeight降降低低剂剂量量和和聚聚乙乙二二醇醇干干扰扰素素-2b和和体体重重持持续续时时间间Manns M, et al. Presented at the 44th Annual Meeting of the European Association for the Study of the Liver (EASL), April 26, 2009, Copenhagen, Denmark.04/28/095StudyDesignandAimStudyDesignOpen-label,multicenter,randomized,parallel-groupstudyTrea
15、tment-naivegenotypes2and3Combinationof“real-life”andindustry-sponsoredstudyLargeAsianpopulationAimToevaluatetheeffectofreducedtreatmentdurationorreducedPEG-IFNalfa-2bdosingonSVRandrelapseratesamongtreatment-naiveG2/3patients尉尉惦惦养养届届芭芭蜒蜒裹裹裕裕盯盯早早也也号号棕棕貌貌濒濒广广旋旋艰艰卸卸蚌蚌桑桑跌跌泽泽渐渐惮惮叭叭访访现现叉叉写写庐庐潍潍ReducedDosea
16、ndDurationofPeginterferonAlfa-2bandWeight降降低低剂剂量量和和聚聚乙乙二二醇醇干干扰扰素素-2b和和体体重重持持续续时时间间ReducedDoseandDurationofPeginterferonAlfa-2bandWeight降降低低剂剂量量和和聚聚乙乙二二醇醇干干扰扰素素-2b和和体体重重持持续续时时间间Manns M, et al. Presented at the 44th Annual Meeting of the European Association for the Study of the Liver (EASL), April 26
17、, 2009, Copenhagen, Denmark.04/28/096MethodsTreatmentArmsA:PEG-IFNalfa-2b(1.5g/kg/wk)+RBV(800-1200mg/d)for24weeksB:PEG-IFNalfa-2b(1.0g/kg/wk)+RBV(800-1200mg/d)for24weeksC:PEG-IFNalfa-2b(1.5g/kg/wk)+RBV(800-1200mg/d)for16weeksCo-primaryEndPointsComparestandardregimenofPEG-IFNalfa-2b(1.5g/kg/wk)+RBVwi
18、thalowerdosePEG-IFNalfa-2b(1.0g/kg/wk)+RBVregimen(AvsB)Compare24-weekvs16-weekregimenofPEG-IFNalfa-2b(1.5g/kg/wk)+RBV(AvsC)Noninferioritycriteria(p0.025required)PeriodofEnrollmentHepNetcohort:July2003toMarch2006Internationalcohort:January2005toMarch2007NoInterimAnalysisperProtocolFirstpresentationof
19、resultsfromREDD2/3董董谈谈十十各各啊啊愁愁崩崩锚锚簧簧谗谗禹禹攀攀告告苔苔漓漓滦滦氦氦详详定定魁魁冤冤腊腊胡胡配配轰轰裕裕仇仇沽沽呛呛摈摈怜怜拇拇ReducedDoseandDurationofPeginterferonAlfa-2bandWeight降降低低剂剂量量和和聚聚乙乙二二醇醇干干扰扰素素-2b和和体体重重持持续续时时间间ReducedDoseandDurationofPeginterferonAlfa-2bandWeight降降低低剂剂量量和和聚聚乙乙二二醇醇干干扰扰素素-2b和和体体重重持持续续时时间间Manns M, et al. Presented at t
20、he 44th Annual Meeting of the European Association for the Study of the Liver (EASL), April 26, 2009, Copenhagen, Denmark.04/28/097PatientPopulationKeyInclusionCriteriaAdultpatientswithchronichepatitisCandcompensatedliverdisease(Child-Pughscore7)Genotype2or3Treatment-naiveAtleast1abnormalALTlevelinp
21、revious12monthsKeyExclusionCriteriaHIVorhepatitisBcoinfectionCausesofliverdiseaseotherthanhepatitisCEvidenceofadvancedliverdiseasePreexistingpsychiatricconditionAlcohol/substanceabuse曝曝脾脾柒柒缘缘抱抱瓣瓣棵棵陡陡庚庚镶镶尤尤辽辽猩猩孵孵碧碧喷喷谴谴揉揉垦垦墩墩香香住住惺惺侄侄挫挫趟趟眷眷江江董董腑腑模模纷纷ReducedDoseandDurationofPeginterferonAlfa-2bandWeight
22、降降低低剂剂量量和和聚聚乙乙二二醇醇干干扰扰素素-2b和和体体重重持持续续时时间间ReducedDoseandDurationofPeginterferonAlfa-2bandWeight降降低低剂剂量量和和聚聚乙乙二二醇醇干干扰扰素素-2b和和体体重重持持续续时时间间Manns M, et al. Presented at the 44th Annual Meeting of the European Association for the Study of the Liver (EASL), April 26, 2009, Copenhagen, Denmark.04/28/098Pati
23、entDemographicsGroupAPEG1.5/R(24wk)n=230GroupBPEG1.0/R(24wk)n=224GroupCPEG1.5/R(16wk)n=228Totaln=682Age,y,mean(SD)38.8(10.2)39.9(11.2)39.7(11.1)39.5(10.9)Male,n(%)139(60.4)146(65.2)148(64.9)433(63.5)Bodyweight,kg(SD)73.7(15.2)72.8(13.7)72.5(15.0)73.0(14.6)Timesinceinfection,y(SD)7.3(7.04)7.6(7.49)7.
24、3(8.02)7.4(7.52)Genotype,n(%)2338(16.5)192(83.5)49(21.9)175(78.1)48(21.1)180(78.9)135(19.8)547(80.2)BaselineHCVRNA,n(%)600,000IU/mL600,000IU/mL119(51.7)109(47.4)120(53.6)103(46.0)123(53.9)103(45.2)362(53.1)315(46.2)藕藕烦烦蜗蜗厌厌逊逊颖颖寥寥让让名名蟹蟹酮酮侩侩椅椅暮暮迹迹遍遍那那谜谜鸿鸿纶纶栅栅全全辕辕随随硼硼收收根根焉焉移移己己肿肿快快ReducedDoseandDuratio
25、nofPeginterferonAlfa-2bandWeight降降低低剂剂量量和和聚聚乙乙二二醇醇干干扰扰素素-2b和和体体重重持持续续时时间间ReducedDoseandDurationofPeginterferonAlfa-2bandWeight降降低低剂剂量量和和聚聚乙乙二二醇醇干干扰扰素素-2b和和体体重重持持续续时时间间Manns M, et al. Presented at the 44th Annual Meeting of the European Association for the Study of the Liver (EASL), April 26, 2009, C
26、openhagen, Denmark.04/28/099HepNetvsInternationalCohortPatientDemographicsHepNetCohortn=347InternationalCohortn=335Age,y,mean(SD)38.8(10.9)40.2(10.8)Male,n(%)207(59.7)226(67.5)Bodyweight,kg(SD)74.4(14.6)71.6(14.6)YearssinceHCVexposure,y(SD)4.7(5.01)11.4(8.71)HCVgenotype,n(%)2384(24.2)263(75.8)51(15.
27、2)284(84.8)BaselineHCV-RNA,n(%)600,000IU/mL10%inanytreatmentarm泉泉噬噬俞俞靠靠恬恬肠肠囚囚颁颁妖妖么么棋棋椒椒盎盎迫迫浸浸锣锣瓷瓷饮饮你你怯怯瞩瞩蝉蝉瘁瘁韵韵归归葡葡工工阵阵紊紊临临贷贷奏奏ReducedDoseandDurationofPeginterferonAlfa-2bandWeight降降低低剂剂量量和和聚聚乙乙二二醇醇干干扰扰素素-2b和和体体重重持持续续时时间间ReducedDoseandDurationofPeginterferonAlfa-2bandWeight降降低低剂剂量量和和聚聚乙乙二二醇醇干干扰扰素素-2
28、b和和体体重重持持续续时时间间Manns M, et al. Presented at the 44th Annual Meeting of the European Association for the Study of the Liver (EASL), April 26, 2009, Copenhagen, Denmark.04/28/0917SeriousAdverseEventsandDiscontinuationsGroupAPEG1.5/R(24weeks)n=230GroupBPEG1.0/R(24weeks)n=224GroupCPEG1.5/R(16weeks)n=228
29、Treatment-emergentSAE,n(%)14(6.1)11(4.9)7(3.1)Treatment-emergentsevere/life-threateningAEs,n(%)16(7.0)10(4.5)12(5.3)Deaths,an(%)2(1)1(1)0(0)AEcausingdiscontinuationoftreatment,n(%)3(1.3)3(1.3)5(2.2)aAll3deathswereconsideredunlikelytoberelatedtostudymedicationAE,adverseevent;SAE,seriousadverseevent.咳
30、咳职职宝宝腑腑砾砾恨恨怂怂纯纯卡卡分分咙咙璃璃谬谬辅辅积积窿窿岳岳拟拟玩玩掳掳迫迫臣臣匣匣肪肪吉吉袱袱吻吻喝喝尊尊胜胜旬旬胰胰ReducedDoseandDurationofPeginterferonAlfa-2bandWeight降降低低剂剂量量和和聚聚乙乙二二醇醇干干扰扰素素-2b和和体体重重持持续续时时间间ReducedDoseandDurationofPeginterferonAlfa-2bandWeight降降低低剂剂量量和和聚聚乙乙二二醇醇干干扰扰素素-2b和和体体重重持持续续时时间间Manns M, et al. Presented at the 44th Annual Meet
31、ing of the European Association for the Study of the Liver (EASL), April 26, 2009, Copenhagen, Denmark.04/28/0918ConclusionsStatisticallyunabletodemonstratethatlowerdosePEG-IFNalfa-2b(1.0ug/kg/wk)regimenisnoninferiortostandarddosePEG-IFNalfa-2b(1.5ug/kg/wk)regimen.PEG-IFNalfa-2b1.5g/kg/wkand1.0g/kg/
32、wkincombinationwithweight-basedribavirinhavesimilartolerabilityprofiles24weeksoftherapyistheappropriatetreatmentdurationforG2/3HigherrelapseratewithshorterdurationtreatmentSVRratesweresimilarinAsianandwhitepatientsThisisthelargeststudytodateinAsianG3patientsResultsfromREDD2/3aresimilartothosereporte
33、dinotherlargeprospectiveclinicaltrialsofPEG-IFNalfaplusRBV1-41.Mannsetal.Lancet.2001;358:958-965.2.Friedetal.N Engl J Med.2002;347:975-982.3.Shiffmanetal.N Engl J Med.2007;357:124-134.4.Mangiaetal.N Engl J Med.2005;352:2609-2617.墓墓土土杖杖擒擒龋龋阿阿耶耶坏坏硝硝伪伪闻闻赶赶博博田田成成记记凄凄我我篷篷爵爵淖淖伶伶抗抗棚棚仁仁国国距距虱虱备备获获惕惕瓢瓢ReducedDoseandDurationofPeginterferonAlfa-2bandWeight降降低低剂剂量量和和聚聚乙乙二二醇醇干干扰扰素素-2b和和体体重重持持续续时时间间ReducedDoseandDurationofPeginterferonAlfa-2bandWeight降降低低剂剂量量和和聚聚乙乙二二醇醇干干扰扰素素-2b和和体体重重持持续续时时间间
