title: Relationship between symptom change, relapse activity and disability progression in multiple sclerosis.
abstract: BACKGROUND
  Symptom changes may serve as a risk factor for relapse activity (RA) and disability progression (DP), which could facilitate multiple sclerosis (MS) treatment decisions.
  
  
  OBJECTIVE
  To assess the relationship of symptom change with RA and DP.
  
  
  METHODS
  We evaluated the relationship of symptom change with subsequent RA and DP using NARCOMS registry data reported over a five-year period. Symptom change was evaluated using both symptom worsening (SW) and average of Performance Scales (APS) scores. Disability progression was defined as a one-point or more increase in Patient-Determined Disease Steps (PDDS) score between two consecutive updates. Repeated measures logistic regression was used to investigate the relationship between symptom change and RA and DP.
  
  
  RESULTS
  SW and APS were both significant predictors of subsequent RA and DP. Both SW and APS have a significant interaction with levels of disability (Mildly Impaired versus Highly Impaired) for the prediction of the subsequent RA or DP. For Mildly Impaired MS subjects, both SW and APS were significant predictors of both RA and DP. However, for Highly Impaired MS subjects, SW did not significantly predict future RA and neither SW nor APS predicted disability progression.
  
  
  CONCLUSIONS
  Changes in self-reported overall symptomatology may precede and predict clinical relapse and future disability progression. The predictive power of symptom changes may only be present at lower levels of disability.
authors.affiliation: Department of Biostatistics, University of Alabama at Birmingham, Birmingham, AL, USA. Electronic address: yuliang@uab.edu.
authors.forename: Yuliang
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Biostatistics, University of Alabama at Birmingham, Birmingham, AL, USA. Electronic address: cjmorgan@uab.edu.
authors.forename: Charity
authors.initials: C
authors.lastname: Morgan
authors.affiliation: Department of Biostatistics, University of Alabama at Birmingham, Birmingham, AL, USA. Electronic address: lindsey.hornung@cchmc.org.
authors.forename: Lindsey
authors.initials: L
authors.lastname: Hornung
authors.affiliation: Division of Neurology, Barrow Neurological Institute, Phoenix, AZ, USA. Electronic address: tuula.tyry@dignityhealth.org.
authors.forename: Tuula
authors.initials: T
authors.lastname: Tyry
authors.affiliation: Department of Biostatistics, University of Alabama at Birmingham, Birmingham, AL, USA. Electronic address: asalter@uab.edu.
authors.forename: Amber R
authors.initials: AR
authors.lastname: Salter
authors.affiliation: Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA. Electronic address: neetu.agashivala@novartis.com.
authors.forename: Neetu
authors.initials: N
authors.lastname: Agashivala
authors.affiliation: Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA. Electronic address: belletd3@hotmail.com.
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Belletti
authors.affiliation: Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA. Electronic address: edward.kim@novartis.com.
authors.forename: Edward
authors.initials: E
authors.lastname: Kim
authors.affiliation: Mellen Center for MS, Cleveland Clinic, Cleveland, USA. Electronic address: foxr@ccf.org.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Fox
authors.affiliation: Department of Biostatistics, University of Alabama at Birmingham, Birmingham, AL, USA. Electronic address: scofield@uab.edu.
authors.forename: Stacey S
authors.initials: SS
authors.lastname: Cofield
authors.affiliation: Department of Biostatistics, University of Alabama at Birmingham, Birmingham, AL, USA. Electronic address: cutterg@uab.edu.
authors.forename: Gary R
authors.initials: GR
authors.lastname: Cutter
mesh_terms: D000328:Adult; D015331:Cohort Studies; D006233:Persons with Disabilities; D018450:Disease Progression; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000453:epidemiology* / Q000503:physiopathology*; D012008:Recurrence
keywords: Disability progression; Disease modifying therapy; Multiple sclerosis; PDDS; Patient-reported outcomes; Relapse activity; Symptom worsening