title: Risk of relapse after natalizumab withdrawal: Results from the French TYSEDMUS cohort.
abstract: OBJECTIVE
  To assess disease activity within 12 months after natalizumab (NZ) discontinuation in a large French postmarketing cohort.
  
  
  METHODS
  In France, patients exposed at least once to NZ were included in the TYSEDMUS observational and multicenter cohort, part of the French NZ Risk Management Plan. Clinical disease activity during the year following NZ discontinuation was assessed in this cohort. Time to first relapse after NZ stop was analyzed using Kaplan-Meier method and potentially associated factors were studied using a multivariate Cox model.
  
  
  RESULTS
  Out of the 4,055 patients with multiple sclerosis (MS) included in TYSEDMUS, 1,253 discontinued NZ and 715 of them had relevant data for our study. The probability of relapse within the year after NZ stop was estimated at 45% (95% confidence interval 0.41-0.49).
  
  
  CONCLUSIONS
  This large and systematic survey of patients with MS after NZ withdrawal allows quantifying the risk of increased disease activity following treatment discontinuation. This study provides large-scale, multicenter, systematic data after NZ cessation in real-life settings.
authors.affiliation: Neurology Department (C.P., S.M., C.L.), Pitié-Salpêtrière Hospital, Paris; Service de Neurologie A, Hôpital Neurologique Pierre Wertheimer (S.V., C.C.), and Neuro-epidemiology and Pharmaco-epidemiology (E.V.G.), Hospices Civils de Lyon, Lyon/Bron; Centre des Neurosciences de Lyon (S.V., C.C.), INSERM 1028 et CNRS UMR5292, Equipe Neuro-oncologie et Neuro-inflammation; Université de Lyon (S.V., C.C.); Observatoire Français de la Sclérose en Plaques (R.C., N.D., Z.U.), Bron; Neurology Department (B.S.), Saint Antoine Hospital, Paris; Agence Nationale de Sécurité des Médicaments (ANSM, formerly Agence Française de Sécurité Sanitaire des Produits de Santé-AFSSAPS) (A.C.), Saint-Denis; and Neurology Department (M.C.), Purpan Hospital, Toulouse, France.
authors.forename: Caroline
authors.initials: C
authors.lastname: Papeix
authors.affiliation: Neurology Department (C.P., S.M., C.L.), Pitié-Salpêtrière Hospital, Paris; Service de Neurologie A, Hôpital Neurologique Pierre Wertheimer (S.V., C.C.), and Neuro-epidemiology and Pharmaco-epidemiology (E.V.G.), Hospices Civils de Lyon, Lyon/Bron; Centre des Neurosciences de Lyon (S.V., C.C.), INSERM 1028 et CNRS UMR5292, Equipe Neuro-oncologie et Neuro-inflammation; Université de Lyon (S.V., C.C.); Observatoire Français de la Sclérose en Plaques (R.C., N.D., Z.U.), Bron; Neurology Department (B.S.), Saint Antoine Hospital, Paris; Agence Nationale de Sécurité des Médicaments (ANSM, formerly Agence Française de Sécurité Sanitaire des Produits de Santé-AFSSAPS) (A.C.), Saint-Denis; and Neurology Department (M.C.), Purpan Hospital, Toulouse, France.
authors.forename: Sandra
authors.initials: S
authors.lastname: Vukusic
authors.affiliation: Neurology Department (C.P., S.M., C.L.), Pitié-Salpêtrière Hospital, Paris; Service de Neurologie A, Hôpital Neurologique Pierre Wertheimer (S.V., C.C.), and Neuro-epidemiology and Pharmaco-epidemiology (E.V.G.), Hospices Civils de Lyon, Lyon/Bron; Centre des Neurosciences de Lyon (S.V., C.C.), INSERM 1028 et CNRS UMR5292, Equipe Neuro-oncologie et Neuro-inflammation; Université de Lyon (S.V., C.C.); Observatoire Français de la Sclérose en Plaques (R.C., N.D., Z.U.), Bron; Neurology Department (B.S.), Saint Antoine Hospital, Paris; Agence Nationale de Sécurité des Médicaments (ANSM, formerly Agence Française de Sécurité Sanitaire des Produits de Santé-AFSSAPS) (A.C.), Saint-Denis; and Neurology Department (M.C.), Purpan Hospital, Toulouse, France.
authors.forename: Romain
authors.initials: R
authors.lastname: Casey
authors.affiliation: Neurology Department (C.P., S.M., C.L.), Pitié-Salpêtrière Hospital, Paris; Service de Neurologie A, Hôpital Neurologique Pierre Wertheimer (S.V., C.C.), and Neuro-epidemiology and Pharmaco-epidemiology (E.V.G.), Hospices Civils de Lyon, Lyon/Bron; Centre des Neurosciences de Lyon (S.V., C.C.), INSERM 1028 et CNRS UMR5292, Equipe Neuro-oncologie et Neuro-inflammation; Université de Lyon (S.V., C.C.); Observatoire Français de la Sclérose en Plaques (R.C., N.D., Z.U.), Bron; Neurology Department (B.S.), Saint Antoine Hospital, Paris; Agence Nationale de Sécurité des Médicaments (ANSM, formerly Agence Française de Sécurité Sanitaire des Produits de Santé-AFSSAPS) (A.C.), Saint-Denis; and Neurology Department (M.C.), Purpan Hospital, Toulouse, France.
authors.forename: Nadine
authors.initials: N
authors.lastname: Debard
authors.affiliation: Neurology Department (C.P., S.M., C.L.), Pitié-Salpêtrière Hospital, Paris; Service de Neurologie A, Hôpital Neurologique Pierre Wertheimer (S.V., C.C.), and Neuro-epidemiology and Pharmaco-epidemiology (E.V.G.), Hospices Civils de Lyon, Lyon/Bron; Centre des Neurosciences de Lyon (S.V., C.C.), INSERM 1028 et CNRS UMR5292, Equipe Neuro-oncologie et Neuro-inflammation; Université de Lyon (S.V., C.C.); Observatoire Français de la Sclérose en Plaques (R.C., N.D., Z.U.), Bron; Neurology Department (B.S.), Saint Antoine Hospital, Paris; Agence Nationale de Sécurité des Médicaments (ANSM, formerly Agence Française de Sécurité Sanitaire des Produits de Santé-AFSSAPS) (A.C.), Saint-Denis; and Neurology Department (M.C.), Purpan Hospital, Toulouse, France.
authors.forename: Bruno
authors.initials: B
authors.lastname: Stankoff
authors.affiliation: Neurology Department (C.P., S.M., C.L.), Pitié-Salpêtrière Hospital, Paris; Service de Neurologie A, Hôpital Neurologique Pierre Wertheimer (S.V., C.C.), and Neuro-epidemiology and Pharmaco-epidemiology (E.V.G.), Hospices Civils de Lyon, Lyon/Bron; Centre des Neurosciences de Lyon (S.V., C.C.), INSERM 1028 et CNRS UMR5292, Equipe Neuro-oncologie et Neuro-inflammation; Université de Lyon (S.V., C.C.); Observatoire Français de la Sclérose en Plaques (R.C., N.D., Z.U.), Bron; Neurology Department (B.S.), Saint Antoine Hospital, Paris; Agence Nationale de Sécurité des Médicaments (ANSM, formerly Agence Française de Sécurité Sanitaire des Produits de Santé-AFSSAPS) (A.C.), Saint-Denis; and Neurology Department (M.C.), Purpan Hospital, Toulouse, France.
authors.forename: Serge
authors.initials: S
authors.lastname: Mrejen
authors.affiliation: Neurology Department (C.P., S.M., C.L.), Pitié-Salpêtrière Hospital, Paris; Service de Neurologie A, Hôpital Neurologique Pierre Wertheimer (S.V., C.C.), and Neuro-epidemiology and Pharmaco-epidemiology (E.V.G.), Hospices Civils de Lyon, Lyon/Bron; Centre des Neurosciences de Lyon (S.V., C.C.), INSERM 1028 et CNRS UMR5292, Equipe Neuro-oncologie et Neuro-inflammation; Université de Lyon (S.V., C.C.); Observatoire Français de la Sclérose en Plaques (R.C., N.D., Z.U.), Bron; Neurology Department (B.S.), Saint Antoine Hospital, Paris; Agence Nationale de Sécurité des Médicaments (ANSM, formerly Agence Française de Sécurité Sanitaire des Produits de Santé-AFSSAPS) (A.C.), Saint-Denis; and Neurology Department (M.C.), Purpan Hospital, Toulouse, France.
authors.forename: Zoe
authors.initials: Z
authors.lastname: Uhry
authors.affiliation: Neurology Department (C.P., S.M., C.L.), Pitié-Salpêtrière Hospital, Paris; Service de Neurologie A, Hôpital Neurologique Pierre Wertheimer (S.V., C.C.), and Neuro-epidemiology and Pharmaco-epidemiology (E.V.G.), Hospices Civils de Lyon, Lyon/Bron; Centre des Neurosciences de Lyon (S.V., C.C.), INSERM 1028 et CNRS UMR5292, Equipe Neuro-oncologie et Neuro-inflammation; Université de Lyon (S.V., C.C.); Observatoire Français de la Sclérose en Plaques (R.C., N.D., Z.U.), Bron; Neurology Department (B.S.), Saint Antoine Hospital, Paris; Agence Nationale de Sécurité des Médicaments (ANSM, formerly Agence Française de Sécurité Sanitaire des Produits de Santé-AFSSAPS) (A.C.), Saint-Denis; and Neurology Department (M.C.), Purpan Hospital, Toulouse, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Van Ganse
authors.affiliation: Neurology Department (C.P., S.M., C.L.), Pitié-Salpêtrière Hospital, Paris; Service de Neurologie A, Hôpital Neurologique Pierre Wertheimer (S.V., C.C.), and Neuro-epidemiology and Pharmaco-epidemiology (E.V.G.), Hospices Civils de Lyon, Lyon/Bron; Centre des Neurosciences de Lyon (S.V., C.C.), INSERM 1028 et CNRS UMR5292, Equipe Neuro-oncologie et Neuro-inflammation; Université de Lyon (S.V., C.C.); Observatoire Français de la Sclérose en Plaques (R.C., N.D., Z.U.), Bron; Neurology Department (B.S.), Saint Antoine Hospital, Paris; Agence Nationale de Sécurité des Médicaments (ANSM, formerly Agence Française de Sécurité Sanitaire des Produits de Santé-AFSSAPS) (A.C.), Saint-Denis; and Neurology Department (M.C.), Purpan Hospital, Toulouse, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Castot
authors.affiliation: Neurology Department (C.P., S.M., C.L.), Pitié-Salpêtrière Hospital, Paris; Service de Neurologie A, Hôpital Neurologique Pierre Wertheimer (S.V., C.C.), and Neuro-epidemiology and Pharmaco-epidemiology (E.V.G.), Hospices Civils de Lyon, Lyon/Bron; Centre des Neurosciences de Lyon (S.V., C.C.), INSERM 1028 et CNRS UMR5292, Equipe Neuro-oncologie et Neuro-inflammation; Université de Lyon (S.V., C.C.); Observatoire Français de la Sclérose en Plaques (R.C., N.D., Z.U.), Bron; Neurology Department (B.S.), Saint Antoine Hospital, Paris; Agence Nationale de Sécurité des Médicaments (ANSM, formerly Agence Française de Sécurité Sanitaire des Produits de Santé-AFSSAPS) (A.C.), Saint-Denis; and Neurology Department (M.C.), Purpan Hospital, Toulouse, France.
authors.forename: Michel
authors.initials: M
authors.lastname: Clanet
authors.affiliation: Neurology Department (C.P., S.M., C.L.), Pitié-Salpêtrière Hospital, Paris; Service de Neurologie A, Hôpital Neurologique Pierre Wertheimer (S.V., C.C.), and Neuro-epidemiology and Pharmaco-epidemiology (E.V.G.), Hospices Civils de Lyon, Lyon/Bron; Centre des Neurosciences de Lyon (S.V., C.C.), INSERM 1028 et CNRS UMR5292, Equipe Neuro-oncologie et Neuro-inflammation; Université de Lyon (S.V., C.C.); Observatoire Français de la Sclérose en Plaques (R.C., N.D., Z.U.), Bron; Neurology Department (B.S.), Saint Antoine Hospital, Paris; Agence Nationale de Sécurité des Médicaments (ANSM, formerly Agence Française de Sécurité Sanitaire des Produits de Santé-AFSSAPS) (A.C.), Saint-Denis; and Neurology Department (M.C.), Purpan Hospital, Toulouse, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Lubetzki
authors.affiliation: Neurology Department (C.P., S.M., C.L.), Pitié-Salpêtrière Hospital, Paris; Service de Neurologie A, Hôpital Neurologique Pierre Wertheimer (S.V., C.C.), and Neuro-epidemiology and Pharmaco-epidemiology (E.V.G.), Hospices Civils de Lyon, Lyon/Bron; Centre des Neurosciences de Lyon (S.V., C.C.), INSERM 1028 et CNRS UMR5292, Equipe Neuro-oncologie et Neuro-inflammation; Université de Lyon (S.V., C.C.); Observatoire Français de la Sclérose en Plaques (R.C., N.D., Z.U.), Bron; Neurology Department (B.S.), Saint Antoine Hospital, Paris; Agence Nationale de Sécurité des Médicaments (ANSM, formerly Agence Française de Sécurité Sanitaire des Produits de Santé-AFSSAPS) (A.C.), Saint-Denis; and Neurology Department (M.C.), Purpan Hospital, Toulouse, France.
authors.forename: Christian
authors.initials: C
authors.lastname: Confavreux