title: Long-term management of natalizumab discontinuation in a large monocentric cohort of multiple sclerosis patients.
abstract: BACKGROUND
  Pivotal and post-marketing studies demonstrated the impressive efficacy and the good tolerability profile of natalizumab in Multiple Sclerosis patients. On the other hand long-term safety of natalizumab therapy is burdened by the risk of progressive multifocal leukoencephalopathy, especially in anti-JCV seropositive patients treated for more than two years. Some of these patients must stop the drug at the risk of disease reactivation.
  
  
  OBJECTIVE
  To evaluate the effects of natalizumab discontinuation in a monocentric cohort of multiple sclerosis patients followed for a mean time of 22.4 months.
  
  
  METHODS
  One hundred and ten patients, who stopped therapy after at least 12 infusions, were followed with periodic clinical and magnetic resonance imaging evaluations. One hundred patients started either immunomodulant therapy (n=90) or fingolimod (n=10) while 10 remained without any drug.
  
  
  RESULTS
  "Disease-activity free" patients were 25% at one year after discontinuation and annualized relapse rate significantly increased from 0.06 to 0.84 (p<0.0001). We found that the risk of reactivation peaked despite alternative treatments between the second and the eighth month after suspension, a so-called "high risk period". During this period the majority of patients showed a return to pre-natalizumab disease activity while 10% of patients presented a "rebound activity". A higher pre-natalizumab disease activity was correlated with an increased risk of reactivation (p=0.004).
  
  
  CONCLUSIONS
  Our data suggest that disease reactivation peaked during a "high risk period" between the second and the eighth month since stopping the drug. During this period no alternative treatments seemed to provide an adequate protection from disease reactivation. Though transient, this phase could be potentially dangerous, therefore we need to develop more effective strategies to deal with this challenge.
authors: Department of Neurology, San Raffaele Scientific Institute, Via Olgettina 48, 20132 Milan, Italy. Electronic address: sangalli.francesca@hsr.it.
authors: Francesca
authors: F
authors: Sangalli
authors: Department of Neurology, San Raffaele Scientific Institute, Via Olgettina 48, 20132 Milan, Italy.
authors: Lucia
authors: L
authors: Moiola
authors: Department of Neurology, San Raffaele Scientific Institute, Via Olgettina 48, 20132 Milan, Italy.
authors: Laura
authors: L
authors: Ferrè
authors: Department of Neurology, San Raffaele Scientific Institute, Via Olgettina 48, 20132 Milan, Italy.
authors: Marta
authors: M
authors: Radaelli
authors: Department of Neurology, San Raffaele Scientific Institute, Via Olgettina 48, 20132 Milan, Italy.
authors: Valeria
authors: V
authors: Barcella
authors: Department of Neurology, San Raffaele Scientific Institute, Via Olgettina 48, 20132 Milan, Italy.
authors: Mariaemma
authors: M
authors: Rodegher
authors: Department of Neurology, San Raffaele Scientific Institute, Via Olgettina 48, 20132 Milan, Italy.
authors: Bruno
authors: B
authors: Colombo
authors: Department of Neurology, San Raffaele Scientific Institute, Via Olgettina 48, 20132 Milan, Italy.
authors: Filippo
authors: F
authors: Martinelli Boneschi
authors: Department of Neurology, San Raffaele Scientific Institute, Via Olgettina 48, 20132 Milan, Italy.
authors: Vittorio
authors: V
authors: Martinelli
authors: Department of Neurology, San Raffaele Scientific Institute, Via Olgettina 48, 20132 Milan, Italy.
authors: Giancarlo
authors: G
authors: Comi
keywords: Discontinuation; Multiple sclerosis; Tysabri