title: Natalizumab discontinuation in patients with multiple sclerosis: Profiling risk and benefits at therapeutic crossroads.
abstract: OBJECTIVE
  The objective of this paper is to estimate the risk of reaching well-established disability milestones after withdrawal of natalizumab (NTZ) due to concern about the risk of progressive multifocal leukoencephalopathy in patients with multiple sclerosis (MS).
  
  
  METHODS
  Data from 415 patients with MS followed-up for six years after starting NTZ were collected from seven tertiary MS centers. The risk of disability worsening, i.e. reaching Expanded Disability Status Scale (EDSS) scores of 4.0 or 6.0, and the likelihood of experiencing a disability reduction of one EDSS point (or more), were assessed by propensity score-adjusted analyses in patients who discontinued and in those still on treatment at the end of follow-up.
  
  
  RESULTS
  A total of 318 patients who received standard NTZ treatment without experiencing evidence of disability worsening in the first two years were included in the six-year follow-up analysis, with 196 (61.6%) still on treatment and 122 (38.4%) discontinuing after a median time of 3.5 years. Patients in the discontinuing group had a more than two-fold increased risk of disability worsening (p = 0.007), and a 68% decreased likelihood of experiencing disability reduction (p = 0.009) compared with the continuing group.
  
  
  CONCLUSIONS
  While discussing the overall risk/benefit profile of NTZ, patients should be advised that, in case of treatment discontinuation, the risk of disability worsening is one in three, and increases to one in two if the EDSS score at NTZ start is above 3.0.
authors.affiliation: Department of Neurology and Psychiatry, Sapienza University, Italy luca.prosperini@uniroma1.it.
authors.forename: Luca
authors.initials: L
authors.lastname: Prosperini
authors.affiliation: MS Centre, S. Antonio Abate Hospital, Italy.
authors.forename: Pietro
authors.initials: P
authors.lastname: Annovazzi
authors.affiliation: Neurologia 2 - CRESM (Centro Riferimento Regionale Sclerosi Multipla), University Hospital San Luigi Gonzaga, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Capobianco
authors.affiliation: Regional Referring MS Center, Spedali Civili of Brescia, Montichiari Hospital, Italy.
authors.forename: Ruggero
authors.initials: R
authors.lastname: Capra
authors.affiliation: Department of Neurosciences Tor Vergata University, Italy/IRCCS Neuromed, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Buttari
authors.affiliation: Department of Neurosciences, S. Camillo-Forlanini Hospital, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Gasperini
authors.affiliation: Department of Neurosciences, S. Camillo-Forlanini Hospital, Italy.
authors.forename: Simonetta
authors.initials: S
authors.lastname: Galgani
authors.affiliation: Neurology Unit, Department Head and Neck, ASL 3 genovese, Genova, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Solaro
authors.affiliation: Department of Neurosciences Tor Vergata University, Italy/S. Lucia Foundation IRCCS, Italy.
authors.forename: Diego
authors.initials: D
authors.lastname: Centonze
authors.affiliation: Neurologia 2 - CRESM (Centro Riferimento Regionale Sclerosi Multipla), University Hospital San Luigi Gonzaga, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Bertolotto
authors.affiliation: Department of Neurology and Psychiatry, Sapienza University, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Pozzilli
authors.affiliation: Department of Neurology and Psychiatry, Sapienza University, ItalyMS Centre, S. Antonio Abate Hospital, ItalyNeurologia 2 - CRESM (Centro Riferimento Regionale Sclerosi Multipla), University Hospital San Luigi Gonzaga, ItalyRegional Referring MS Center, Spedali Civili of Brescia, Montichiari Hospital, ItalyDepartment of Neurosciences Tor Vergata University, Italy/IRCCS Neuromed, ItalyDepartment of Neurosciences, S. Camillo-Forlanini Hospital, ItalyDepartment of Neurosciences, S. Camillo-Forlanini Hospital, ItalyNeurology Unit, Department Head and Neck, ASL 3 genovese, Genova, ItalyDepartment of Neurosciences Tor Vergata University, Italy/S. Lucia Foundation IRCCS, ItalyNeurologia 2 - CRESM (Centro Riferimento Regionale Sclerosi Multipla), University Hospital San Luigi Gonzaga, ItalyDepartment of Neurology and Psychiatry, Sapienza University, ItalyMS Centre, S. Antonio Abate Hospital, Italy.
authors.forename: Angelo
authors.initials: A
authors.lastname: Ghezzi
mesh_terms: D000293:Adolescent; D000328:Adult; D005260:Female; D006801:Humans; D007968:Leukoencephalopathy, Progressive Multifocal / Q000453:epidemiology* / Q000209:etiology; D008297:Male; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000188:drug therapy*; D000069442:Natalizumab / Q000009:adverse effects / Q000627:therapeutic use*; D009894:Opportunistic Infections / Q000453:epidemiology* / Q000209:etiology; D011446:Prospective Studies; D018570:Risk Assessment; D028761:Withholding Treatment; D055815:Young Adult
chemical_list: D000069442:Natalizumab
keywords: Natalizumab; disability; discontinuation; progressive multifocal leukoencephalopathy