title: Switching multiple sclerosis patients with breakthrough disease to second-line therapy.
abstract: BACKGROUND
  Multiple sclerosis (MS) patients with breakthrough disease on immunomodulatory drugs are frequently offered to switch to natalizumab or immunosuppressants. The effect of natalizumab monotherapy in patients with breakthrough disease is unknown.
  
  
  METHODS
  This is an open-label retrospective cohort study of 993 patients seen at least four times at the University of California San Francisco MS Center, 95 had breakthrough disease on first-line therapy (60 patients switched to natalizumab, 22 to immunosuppressants and 13 declined the switch [non-switchers]). We used Poisson regression adjusted for potential confounders to compare the relapse rate within and across groups before and after the switch.
  
  
  RESULTS
  In the within-group analyses, the relapse rate decreased by 70% (95% CI 50,82%; p<0.001) in switchers to natalizumab and by 77% (95% CI 59,87%; p<0.001) in switchers to immunosuppressants; relapse rate in non-switchers did not decrease (6%, p =  0.87). Relative to the reduction among non-switchers, the relapse rate was reduced by 68% among natalizumab switchers (95% CI 19,87%; p = 0.017) and by 76% among the immunosuppressant switchers (95% CI 36,91%; p = 0.004).
  
  
  CONCLUSIONS
  Switching to natalizumab or immunosuppressants in patients with breakthrough disease is effective in reducing clinical activity of relapsing MS. The magnitude of the effect and the risk-benefit ratio should be evaluated in randomized clinical trials and prospective cohort studies.
authors.affiliation: Multiple Sclerosis Center, Department of Neurology, University of California San Francisco, San Francisco, California, USA.
authors.forename: Tamara
authors.initials: T
authors.lastname: Castillo-Trivino
authors.forename: Ellen M
authors.initials: EM
authors.lastname: Mowry
authors.forename: Alberto
authors.initials: A
authors.lastname: Gajofatto
authors.forename: Dorothee
authors.initials: D
authors.lastname: Chabas
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Crabtree-Hartman
authors.forename: Bruce A
authors.initials: BA
authors.lastname: Cree
authors.forename: Douglas S
authors.initials: DS
authors.lastname: Goodin
authors.forename: Ari J
authors.initials: AJ
authors.lastname: Green
authors.forename: Darin T
authors.initials: DT
authors.lastname: Okuda
authors.forename: Daniel
authors.initials: D
authors.lastname: Pelletier
authors.forename: Scott S
authors.initials: SS
authors.lastname: Zamvil
authors.forename: Eric
authors.initials: E
authors.lastname: Vittinghoff
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Waubant
mesh_terms: D000328:Adult; D000465:Algorithms; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D017024:Chemotherapy, Adjuvant; D015331:Cohort Studies; D018450:Disease Progression; D057915:Drug Substitution / Q000379:methods; D005260:Female; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use*; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000188:drug therapy* / Q000473:pathology; D000069442:Natalizumab; D012008:Recurrence; D012189:Retrospective Studies
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D007155:Immunologic Factors; D007166:Immunosuppressive Agents; D000069442:Natalizumab