诱导、升级、降级、停药：多发​​性硬化症的治疗决策.pdf

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1、Induction,Escalation,De-Escalation,Discontinuation:Treatment Decisions Over a Lifetime of MSJohn R.Corboy,MDCharles Elliot Morris Chair of Neurology,CU SOMMedical Director,RMMSC at CUApril 6,2024Disclosures Grants NIH/ITN,PCORI,NMSS,EMD Serono Consulting Clene Nanoscience,Bristol Meyers Squib Editin

2、g Annals of Neurology Medical Director Rocky Mountain MS CenterGoal of MS TherapyLife-Long Brain/Spine Health3Changes Through Lifetime Pathological Clinical-less new relapses,some with slow progression Radiological:MRI w less new active lesions,more SELs Biomarkers:NfL,GFAP,others Treatment Behavior

3、al Symptomatic Immunotherapy:Disease Modifying Therapies(DMTs)Neuroprotection Remyelination RegenerationMS PathogenesisInflammation and Neurodegeneration Inflammation due to adaptive immune dysfunction most marked early in coursePathologically new,active lesions with trafficking WBCs/adaptive immune

4、 system Relapses,new enhancing MRI lesions early,then diminish over timeProgression Independent of Relapse Activity(PIRA)important,less common Neurodegeneration occurs early,and accumulates over timeB Cell meningeal follicles and activated microglia on path;innate immune system dysfunction;compartme

5、ntalized inflammation is more prominentPhase Rim Lesions(PRLs)and Slowly Expanding Lesions on MRI scansAccumulation of brain atrophy,T1 holes on MRIPIRA even more frequent,PPMS and SPMSDo presently-available MS DMTs treat both equally?Likely not2017The Evolving MS Treatment LandscapePhase IIIFDA-App

6、roved Therapies199520002005201020112012Aubagio(teriflunomide)Tecfidera(dimethyl fumarate)Extavia(IFN-1b)Gilenya(fingolimod)Tysabri(natalizumab)Betaseron(IFN-1b)Copaxone(glatiramer acetate)Avonex(IFN-1a)Rebif(IFN-1a)Novantrone(mitoxantrone)20132014Ocrevus(ocrelizumab)Zinbryta(Daclizumab)Injectable Th