title: Relapsing multiple sclerosis patients treated with disease modifying therapy exhibit highly variable disease progression: a predictive model.
abstract: OBJECTIVE
  To describe a "new natural history" of multiple sclerosis (MS), characterizing three patterns of progression in Relapsing MS (RMS) patients during the "treatment era," using newly developed definitions. By utilizing our simple model we intend to predict which patients are most likely to reach an EDSS of 6.0.
  
  
  METHODS
  We stratified MS progression into three distinct patterns: aggressive MS (AMS), intermediate MS (IMS) and mild MS (MMS), based on Expanded Disability Status Scale (EDSS) score rate of change. These groups were compared for progression of EDSS before and after reaching these definitions.
  
  
  RESULTS
  The three groups remained significantly different in terms of disability throughout their disease courses p ≤ 0.001; 98% of the patients used disease modifying treatments (DMTs). AMS patients represent a significantly more disabling and aggressive form of MS than the IMS group.
  
  
  CONCLUSIONS
  Transition from relatively mild MS to aggressive course may begin at any time in the first 15 years, despite DMTs. Our definition for AMS is unique and identifies a group of patients who become permanently disabled within two years after a variable amount of time in a benign phase, despite treatment with modern DMTs.
authors.affiliation: Allegheny General Hospital, Department of Neurology, Pittsburgh, USA; Drexel University College of Medicine, Department of Neurology, Pittsburgh, USA.
authors.forename: Thomas F
authors.initials: TF
authors.lastname: Scott
authors.affiliation: Drexel University College of Medicine, Department of Neurology, Pittsburgh, USA. Electronic address: chrishackett@live.com.
authors.forename: Christopher T
authors.initials: CT
authors.lastname: Hackett
authors.affiliation: Drexel University College of Medicine, Department of Neurosurgery, Pittsburgh, USA; Carnegie Mellon University, Department of Biomedical Engineering, Pittsburgh, USA; Allegheny General Hospital, Department of Neurosurgery, Pittsburgh, USA.
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Quigley
authors.affiliation: Allegheny General Hospital, Department of Neurology, Pittsburgh, USA; Drexel University College of Medicine, Department of Neurology, Pittsburgh, USA.
authors.forename: Carol J
authors.initials: CJ
authors.lastname: Schramke
mesh_terms: D000328:Adult; D017668:Age of Onset; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use; D004185:Disability Evaluation; D018450:Disease Progression; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D008962:Models, Theoretical; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000145:classification / Q000628:therapy*; D000069442:Natalizumab; D012008:Recurrence; D016019:Survival Analysis
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000069442:Natalizumab
keywords: Aggressive; DMT; Multiple sclerosis; Natural history; Progression