title: Discontinuation of disease-modifying therapies in multiple sclerosis - Clinical outcome and prognostic factors.
abstract: BACKGROUND
  Stable disease course may prompt consideration of disease-modifying treatment (DMT) discontinuation in relapsing-remitting multiple sclerosis (RRMS).
  
  
  OBJECTIVE
  To investigate the clinical outcome after DMT discontinuation and to identify predictive factors supporting decision-making.
  
  
  METHODS
  We included 221 RRMS patients, who discontinued DMT after ⩾12 months and had documented follow-up ⩾2 years after discontinuation. Hazard ratios (HRs) with 95% confidence intervals (CIs) regarding relapse and disability progression after DMT discontinuation were calculated from Cox regression models.
  
  
  RESULTS
  Age >45 years at discontinuation (HR = 0.47, CI = 0.23-0.95, p = 0.038), absence of relapses for ⩾4 years on DMT before discontinuation (HR = 0.29, CI = 0.10-0.82, p = 0.020) and absence of contrast enhancing lesions (HR = 0.46, CI = 0.28-0.78, p = 0.004) were independent predictors of absence of relapse after discontinuation. Age >45 years and absence of relapses ⩾4 years on DMT combined had an HR of 0.06 (CI = 0.01-0.44, p < 0.001). Higher Expanded Disability Status Scale (EDSS) at discontinuation, age >45 years and longer disease duration were significantly associated with disability progression after discontinuation.
  
  
  CONCLUSIONS
  While freedom from further disease activity is generally unpredictable, there is a subset of patients (age ⩾45 years, DMT intake ⩾4 years without evidence of clinical or radiological disease activity) having a high likelihood of remaining relapse-free after DMT discontinuation. However, close clinical monitoring for recurrent disease activity is mandatory after discontinuing treatment.
authors.affiliation: Clinical Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Bsteh
authors.affiliation: Clinical Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria.
authors.forename: Julia
authors.initials: J
authors.lastname: Feige
authors.affiliation: Clinical Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria.
authors.forename: Rainer
authors.initials: R
authors.lastname: Ehling
authors.affiliation: Clinical Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria.
authors.forename: Michael
authors.initials: M
authors.lastname: Auer
authors.affiliation: Clinical Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria.
authors.forename: Harald
authors.initials: H
authors.lastname: Hegen
authors.affiliation: Clinical Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria.
authors.forename: Franziska
authors.initials: F
authors.lastname: Di Pauli
authors.affiliation: Clinical Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria.
authors.forename: Florian
authors.initials: F
authors.lastname: Deisenhammer
authors.affiliation: Clinical Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria.
authors.forename: Markus
authors.initials: M
authors.lastname: Reindl
authors.affiliation: Clinical Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria.
authors.forename: Thomas
authors.initials: T
authors.lastname: Berger
mesh_terms: D000328:Adult; D000367:Age Factors; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007155:Immunologic Factors; D008297:Male; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000188:drug therapy*; D017063:Outcome Assessment, Health Care; D011379:Prognosis; D012008:Recurrence; D012189:Retrospective Studies; D012720:Severity of Illness Index
chemical_list: D007155:Immunologic Factors
keywords: Multiple sclerosis; discontinuation; disease-modifying therapy; prognosis; progression; relapse