title: Evaluation of no evidence of disease activity in a 7-year longitudinal multiple sclerosis cohort.
abstract: OBJECTIVE
  With multiple and increasingly effective therapies for relapsing forms of multiple sclerosis (MS), disease-free status or no evidence of disease activity (NEDA) has become a treatment goal and a new outcome measure. However, the persistence of NEDA over time and its predictive power for long-term prognosis are unknown.
  
  
  OBJECTIVE
  To investigate NEDA during 7 years as measured by relapses, disability progression, and yearly magnetic resonance imaging (MRI).
  
  
  METHODS
  Patients were selected from the 2200-patient Comprehensive Longitudinal Investigation of Multiple Sclerosis at Brigham and Women's Hospital (CLIMB) cohort study. Patients were required to have an initial diagnosis of clinically isolated syndrome or relapsing-remitting MS and a minimum of 7 years of prospective follow-up that included yearly brain MRI and biannual clinical visits (n = 219). Patients were analyzed independent of disease-modifying therapy. Patients were classified as having early (recent-onset) MS if they were 5 years or less from their first MS symptom at enrollment or otherwise considered to have established MS (>5 years from onset).
  
  
  METHODS
  NEDA was defined as a composite that consisted of absence of relapses, no sustained Expanded Disability Status Scale score progression, and no new or enlarging T2 or T1 gadolinium-enhancing lesions on annual MRI. Relapses, progression, and MRI changes were also investigated as individual outcomes.
  
  
  RESULTS
  A total of 99 of 215 patients (46.0%) had NEDA for clinical and MRI measures at 1 year, but only 17 of 216 (7.9%) maintained NEDA status after 7 years. No differences were found in NEDA status between patients with early vs established MS. A dissociation was found between clinical and MRI disease activity. Each year, 30.6% (64 of 209) to 42.9% (93 of 217) of the cohort had evidence of either clinical or MRI disease activity but not both. NEDA at 2 years had a positive predictive value of 78.3% for no progression (Expanded Disability Status Scale score change ≤0.5) at 7 years. Only minor improvement was found in the positive predictive values with additional follow-up of 1 to 3 years.
  
  
  CONCLUSIONS
  NEDA is difficult to sustain long term even with treatment. NEDA status at 2 years may be optimal in terms of prognostic value in the longer term. Our results provide a basis for investigating NEDA as an outcome measure and treatment goal and for evaluating the effect of new MS drugs on NEDA.
authors.affiliation: Partners Multiple Sclerosis Center, Brigham and Women's Hospital, Boston, Massachusetts.
authors.forename: Dalia L
authors.initials: DL
authors.lastname: Rotstein
authors.affiliation: Partners Multiple Sclerosis Center, Brigham and Women's Hospital, Boston, Massachusetts2Biostatistics Center, Massachusetts General Hospital, Brookline, Massachusetts.
authors.forename: Brian C
authors.initials: BC
authors.lastname: Healy
authors.affiliation: Partners Multiple Sclerosis Center, Brigham and Women's Hospital, Boston, Massachusetts.
authors.forename: Muhammad T
authors.initials: MT
authors.lastname: Malik
authors.affiliation: Partners Multiple Sclerosis Center, Brigham and Women's Hospital, Boston, Massachusetts.
authors.forename: Tanuja
authors.initials: T
authors.lastname: Chitnis
authors.affiliation: Partners Multiple Sclerosis Center, Brigham and Women's Hospital, Boston, Massachusetts.
authors.forename: Howard L
authors.initials: HL
authors.lastname: Weiner
mesh_terms: D000328:Adult; D004185:Disability Evaluation; D018450:Disease Progression; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000175:diagnosis* / Q000473:pathology / Q000503:physiopathology; D017063:Outcome Assessment, Health Care; D011237:Predictive Value of Tests; D011379:Prognosis; D012008:Recurrence