title: Escalation to natalizumab or switching among immunomodulators in relapsing multiple sclerosis.
abstract: OBJECTIVE
  To evaluate whether an escalation approach was more effective in suppressing clinical and magnetic resonance imaging (MRI) activity than switching among immunomodulators in relapsing-remitting multiple sclerosis (RRMS) patients.
  
  
  METHODS
  In this post-marketing, prospective, observational study in two Italian multiple sclerosis (MS) centres, a total of 285 RRMS patients who failed a first-line treatment with interferon beta (IFNβ) or glatiramer acetate (GA) were considered. Patients were subdivided according to the strategy adopted after the failure (defined as the occurrence of ≥2 relapses or 1 relapse with residual disability): the switching (SWI) group, i.e. those switched among different IFNβ formulations, or from IFNβ to GA and vice versa; and the escalating (ESC) group, i.e. those escalated to natalizumab. Proportions of patients free from different types of disease activity (relapses, sustained disability progression, new active lesions on MRI, or a combination of them) were calculated at 12 and 24 months. Since patients were not randomized to treatment group, propensity score (PS)-adjusted Cox regression models were built to control for several potential confounders.
  
  
  RESULTS
  At 12 months there were no differences between the two groups in proportions of patients free from relapse, disability progression, MRI activity, and combined activity. After 24 months we observed greater proportions of patients in the ESC than SWI group free from relapse (p < 0.0001), disability progression (p = 0.0045), MRI activity (p = 0.0003), and combined activity (p < 0.0001). PS-adjusted models confirmed these findings, with hazard ratios ranging from 0.38 to 0.56 favours the ESC group.
  
  
  CONCLUSIONS
  We suggest that an escalation to natalizumab is more effective than switching among immunomodulators in RRMS patients who failed a first-line treatment.
authors.affiliation: Department of Neurology and Psychiatry, Multiple Sclerosis Centre, S. Andrea Hospital, Sapienza University, Rome, Italy. luca.prosperini@uniroma1.it
authors.forename: Luca
authors.initials: L
authors.lastname: Prosperini
authors.forename: Costanza
authors.initials: C
authors.lastname: Giannì
authors.forename: Laura
authors.initials: L
authors.lastname: Leonardi
authors.forename: Laura
authors.initials: L
authors.lastname: De Giglio
authors.forename: Giovanna
authors.initials: G
authors.lastname: Borriello
authors.forename: Simonetta
authors.initials: S
authors.lastname: Galgani
authors.forename: Carlo
authors.initials: C
authors.lastname: Pozzilli
authors.forename: Claudio
authors.initials: C
authors.lastname: Gasperini
mesh_terms: D000328:Adult; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D001921:Brain / Q000473:pathology; D005260:Female; D000068717:Glatiramer Acetate; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use; D056747:Immunomodulation; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D016899:Interferon-beta / Q000627:therapeutic use*; D008279:Magnetic Resonance Imaging; D008297:Male; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000188:drug therapy* / Q000473:pathology; D000069442:Natalizumab; D010455:Peptides / Q000627:therapeutic use*
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D007155:Immunologic Factors; D007166:Immunosuppressive Agents; D000069442:Natalizumab; D010455:Peptides; D000068717:Glatiramer Acetate; D016899:Interferon-beta