title: Switching from natalizumab to fingolimod in multiple sclerosis: a French prospective study.
abstract: OBJECTIVE
  The safety and efficacy of switching from natalizumab to fingolimod have not yet been evaluated in a large cohort of patients with multiple sclerosis (MS) to our knowledge.
  
  
  OBJECTIVE
  To collect data from patients with MS switching from natalizumab to fingolimod.
  
  
  METHODS
  The Enquête Nationale sur l'Introduction du Fingolimod en Relais au Natalizumab (ENIGM) study, a survey-based, observational multicenter cohort study among MS tertiary referral centers. Participants were patients for whom a switch from natalizumab to fingolimod was planned. Clinical data were collected on natalizumab treatment, duration and management of the washout period (WP), and relapse or adverse events during the WP and after the initiation of fingolimod.
  
  
  METHODS
  Occurrence of MS relapse during the WP or during a 6-month follow-up period after the initiation of fingolimod.
  
  
  RESULTS
  Thirty-six French MS tertiary referral centers participated. In total, 333 patients with MS switched from natalizumab to fingolimod after a mean of 31 natalizumab infusions (female to male ratio, 2.36; mean age, 41 years; and Expanded Disability Status Scale score at the initiation of natalizumab, 3.6). Seventy-one percent were seropositive for the JC polyomavirus. The Expanded Disability Status Scale score remained stable for patients receiving natalizumab. Twenty-seven percent of patients relapsed during the WP. A WP shorter than 3 months was associated with a lower risk of relapse (odds ratio, 0.23; P = .001) and with less disease activity before natalizumab initiation (P = .03). Patients who stopped natalizumab because of poor tolerance or lack of efficacy also had a higher risk of relapse (odds ratio, 3.20; P = .004). Twenty percent of patients relapsed during the first 6 months of fingolimod therapy. Three percent stopped fingolimod for efficacy, tolerance, or compliance issues. In the multivariate analysis, the occurrence of relapse during the WP was the only significant prognostic factor for relapse during fingolimod therapy (odds ratio, 3.80; P = .05).
  
  
  CONCLUSIONS
  In this study, switching from natalizumab to fingolimod was associated with a risk of MS reactivation during the WP or shortly after fingolimod initiation. The WP should be shorter than 3 months.
authors.affiliation: Department of Neurology, University Hospital of Nice, Nice, France.
authors.forename: Mikael
authors.initials: M
authors.lastname: Cohen
authors.affiliation: Department of Neurology, Salpêtrière Hospital, Paris, France.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Maillart
authors.affiliation: Department of Neurology, University Hospital of Reims, Reims, France.
authors.forename: Ayman
authors.initials: A
authors.lastname: Tourbah
authors.affiliation: Department of Neurology, University Hospital of Strasbourg, Strasbourg, France.
authors.forename: Jérôme
authors.initials: J
authors.lastname: De Sèze
authors.affiliation: Department of Neurology, University Hospital of Lyon, Lyon, France.
authors.forename: Sandra
authors.initials: S
authors.lastname: Vukusic
authors.affiliation: Department of Neurology, University Hospital of Toulouse, Toulouse, France.
authors.forename: David
authors.initials: D
authors.lastname: Brassat
authors.affiliation: Department of Neurology, University Hospital of La Rochelle, La Rochelle, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Anne
authors.affiliation: Department of Neurology, University Hospital of Nantes, Nantes, France.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Wiertlewski
authors.affiliation: Department of Neurology, University Hospital of Montpellier, Montpellier, France.
authors.forename: William
authors.initials: W
authors.lastname: Camu
authors.affiliation: Department of Neurology, University Hospital of Mulhouse, Mulhouse, France.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Courtois
authors.affiliation: Department of Neurology, University Hospital of Bordeaux, Bordeaux, France.
authors.forename: Aurélie
authors.initials: A
authors.lastname: Ruet
authors.affiliation: Department of Neurology, University Hospital of Nancy, Nancy, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Debouverie
authors.affiliation: Department of Neurology, University Hospital of Rennes, Rennes, France.
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Le Page
authors.affiliation: Department of Neurology, University Hospital of Grenoble, Grenoble, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Casez
authors.affiliation: Department of Neurology, University Hospital of Poissy, Poissy, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Heinzlef
authors.affiliation: Department of Neurology, Tenon Hospital, Paris, France.
authors.forename: Bruno
authors.initials: B
authors.lastname: Stankoff
authors.affiliation: Department of Neurology, University Hospital of Rouen, Rouen, France.
authors.forename: Bertrand
authors.initials: B
authors.lastname: Bourre
authors.affiliation: Department of Neurology, University Hospital of Nimes, Nimes, France.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Castelnovo
authors.affiliation: Department of Neurology, University Hospital of Marseille, Marseille, France.
authors.forename: Audrey
authors.initials: A
authors.lastname: Rico
authors.affiliation: Department of Neurology, University Hospital of Besançon, Besançon, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Berger
authors.affiliation: Department of Neurology, University Hospital of Saint Etienne, Saint Etienne, France.
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Camdessanche
authors.affiliation: Department of Neurology, University Hospital of Caen, Caen, France.
authors.forename: Gilles
authors.initials: G
authors.lastname: Defer
authors.affiliation: Department of Neurology, University Hospital of Clermont Ferrand, Clermont Ferrand, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Clavelou
authors.affiliation: Department of Neurology, University Hospital of Amiens, Amiens, France.
authors.forename: Abdullatif
authors.initials: A
authors.lastname: Al Khedr
authors.affiliation: Department of Neurology, University Hospital of Lille, Lille, France.
authors.forename: Hélène
authors.initials: H
authors.lastname: Zephir
authors.affiliation: Department of Neurology, University Hospital of Dijon, Dijon, France.
authors.forename: Agnès
authors.initials: A
authors.lastname: Fromont
authors.affiliation: Department of Neurology, Salpêtrière Hospital, Paris, France.
authors.forename: Caroline
authors.initials: C
authors.lastname: Papeix
authors.affiliation: Department of Neurology, University Hospital of Mulhouse, Mulhouse, France.
authors.forename: Bruno
authors.initials: B
authors.lastname: Brochet
authors.affiliation: Department of Neurology, University Hospital of Nimes, Nimes, France.
authors.forename: Jean
authors.initials: J
authors.lastname: Pelletier
authors.affiliation: Department of Neurology, University Hospital of Nice, Nice, France.
authors.forename: Christine
authors.initials: C
authors.lastname: Lebrun
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D015331:Cohort Studies; D057915:Drug Substitution / Q000379:methods* / Q000639:trends; D005260:Female; D000068876:Fingolimod Hydrochloride; D005602:France / Q000453:epidemiology; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000175:diagnosis / Q000188:drug therapy* / Q000453:epidemiology; D000069442:Natalizumab; D011409:Propylene Glycols / Q000627:therapeutic use*; D011446:Prospective Studies; D012307:Risk Factors; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D062606:Tertiary Care Centers; D055815:Young Adult
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D007166:Immunosuppressive Agents; D000069442:Natalizumab; D011409:Propylene Glycols; D000068876:Fingolimod Hydrochloride; D013110:Sphingosine