title: Long-term evolution of multiple sclerosis disability in the treatment era.
abstract: To characterize the accrual of long-term disability in a cohort of actively treated multiple sclerosis (MS) patients and to assess whether clinical and magnetic resonance imaging (MRI) data used in clinical trials have long-term prognostic value.
  
  
  
  This is a prospective study of 517 actively managed MS patients enrolled at a single center.
  
  
  
  More than 91% of patients were retained, with data ascertained up to 10 years after the baseline visit. At this last assessment, neurologic disability as measured by the Expanded Disability Status Scale (EDSS) was stable or improved compared to baseline in 41% of patients. Subjects with no evidence of disease activity (NEDA) by clinical and MRI criteria during the first 2 years had long-term outcomes that were no different from those of the cohort as a whole. 25-OH vitamin D serum levels were inversely associated with short-term MS disease activity; however, these levels had no association with long-term disability. At a median time of 16.8 years after disease onset, 10.7% (95% confidence interval [CI] = 7.2-14%) of patients reached an EDSS ≥ 6, and 18.1% (95% CI = 13.5-22.5%) evolved from relapsing MS to secondary progressive MS (SPMS).
  
  
  
  Rates of worsening and evolution to SPMS were substantially lower when compared to earlier natural history studies. Notably, the NEDA 2-year endpoint was not a predictor of long-term stability. Finally, the data call into question the utility of annual MRI assessments as a treat-to-target approach for MS care. Ann Neurol 2016;80:499-510.
authors.affiliation: Department of Neurology, University of California, San Francisco, San Francisco, CA. Bruce.Cree@ucsf.edu.
authors.forename: Bruce A C
authors.initials: BA
authors.lastname: Cree
authors.affiliation: Department of Neurology, University of California, San Francisco, San Francisco, CA.
authors.forename: Pierre-Antoine
authors.initials: PA
authors.lastname: Gourraud
authors.affiliation: Department of Neurology, University of California, San Francisco, San Francisco, CA.
authors.forename: Jorge R
authors.initials: JR
authors.lastname: Oksenberg
authors.affiliation: Department of Neurology, University of California, San Francisco, San Francisco, CA.
authors.forename: Carolyn
authors.initials: C
authors.lastname: Bevan
authors.affiliation: Department of Neurology, University of California, San Francisco, San Francisco, CA.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Crabtree-Hartman
authors.affiliation: Department of Neurology, University of California, San Francisco, San Francisco, CA.
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Gelfand
authors.affiliation: Department of Neurology, University of California, San Francisco, San Francisco, CA.
authors.forename: Douglas S
authors.initials: DS
authors.lastname: Goodin
authors.affiliation: Department of Neurology, University of California, San Francisco, San Francisco, CA.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Graves
authors.affiliation: Department of Neurology, University of California, San Francisco, San Francisco, CA.
authors.forename: Ari J
authors.initials: AJ
authors.lastname: Green
authors.affiliation: Department of Neurology, University of California, San Francisco, San Francisco, CA.
authors.forename: Ellen
authors.initials: E
authors.lastname: Mowry
authors.affiliation: Department of Neurology, University of Texas Southwestern Medical Center, Dallas, TX.
authors.forename: Darin T
authors.initials: DT
authors.lastname: Okuda
authors.affiliation: Department of Neurology, University of Southern California, Los Angeles, CA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Pelletier
authors.affiliation: Department of Neurology, University of California, San Francisco, San Francisco, CA.
authors.forename: H-Christian
authors.initials: HC
authors.lastname: von Büdingen
authors.affiliation: Department of Neurology, University of California, San Francisco, San Francisco, CA.
authors.forename: Scott S
authors.initials: SS
authors.lastname: Zamvil
authors.affiliation: Department of Neurology, University of California, San Francisco, San Francisco, CA.
authors.forename: Alisha
authors.initials: A
authors.lastname: Agrawal
authors.affiliation: Department of Neurology, University of California, San Francisco, San Francisco, CA.
authors.forename: Stacy
authors.initials: S
authors.lastname: Caillier
authors.affiliation: Department of Neurology, University of California, San Francisco, San Francisco, CA.
authors.forename: Caroline
authors.initials: C
authors.lastname: Ciocca
authors.affiliation: Department of Neurology, University of California, San Francisco, San Francisco, CA.
authors.forename: Refujia
authors.initials: R
authors.lastname: Gomez
authors.affiliation: Department of Neurology, University of California, San Francisco, San Francisco, CA.
authors.forename: Rachel
authors.initials: R
authors.lastname: Kanner
authors.affiliation: Department of Neurology, University of California, San Francisco, San Francisco, CA.
authors.forename: Robin
authors.initials: R
authors.lastname: Lincoln
authors.affiliation: Department of Neurology, University of California, San Francisco, San Francisco, CA.
authors.forename: Antoine
authors.initials: A
authors.lastname: Lizee
authors.affiliation: Department of Neurology, University of California, San Francisco, San Francisco, CA.
authors.forename: Pamela
authors.initials: P
authors.lastname: Qualley
authors.affiliation: Department of Neurology, University of California, San Francisco, San Francisco, CA.
authors.forename: Adam
authors.initials: A
authors.lastname: Santaniello
authors.affiliation: Department of Neurology, University of California, San Francisco, San Francisco, CA.
authors.forename: Leena
authors.initials: L
authors.lastname: Suleiman
authors.affiliation: Department of Neurology, University of California, San Francisco, San Francisco, CA.
authors.forename: Monica
authors.initials: M
authors.lastname: Bucci
authors.affiliation: Department of Neurology, University of California, San Francisco, San Francisco, CA.
authors.forename: Valentina
authors.initials: V
authors.lastname: Panara
authors.affiliation: Department of Neurology, University of California, San Francisco, San Francisco, CA.
authors.forename: Nico
authors.initials: N
authors.lastname: Papinutto
authors.affiliation: Department of Neurology, University of California, San Francisco, San Francisco, CA.
authors.forename: William A
authors.initials: WA
authors.lastname: Stern
authors.affiliation: Department of Neurology, University of California, San Francisco, San Francisco, CA.
authors.forename: Alyssa H
authors.initials: AH
authors.lastname: Zhu
authors.affiliation: Department of Biostatistics, University of Alabama at Birmingham, Birmingham, AL.
authors.forename: Gary R
authors.initials: GR
authors.lastname: Cutter
authors.affiliation: Department of Neurology, University of California, San Francisco, San Francisco, CA.
authors.forename: Sergio
authors.initials: S
authors.lastname: Baranzini
authors.affiliation: Department of Neurology, University of California, San Francisco, San Francisco, CA.
authors.forename: Roland G
authors.initials: RG
authors.lastname: Henry
authors.affiliation: Department of Neurology, University of California, San Francisco, San Francisco, CA.
authors.forename: Stephen L
authors.initials: SL
authors.lastname: Hauser
mesh_terms: D000328:Adult; D006233:Persons with Disabilities; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D020528:Multiple Sclerosis, Chronic Progressive / Q000000981:diagnostic imaging* / Q000188:drug therapy / Q000503:physiopathology*; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000000981:diagnostic imaging* / Q000188:drug therapy / Q000503:physiopathology*; D017063:Outcome Assessment, Health Care; D011379:Prognosis; D012720:Severity of Illness Index