title: Efficacy and safety of natalizumab in multiple sclerosis: interim observational programme results.
abstract: BACKGROUND
  Clinical trials established the efficacy and safety of natalizumab. Data are needed over longer periods of time and in the clinical practice setting.
  
  
  OBJECTIVE
  To evaluate long-term safety of natalizumab and its impact on annualised relapse rate and Expanded Disability Status Scale (EDSS) progression in patients with relapsing-remitting multiple sclerosis (RRMS).
  
  
  METHODS
  The Tysabri (natalizumab) Observational Program (TOP) is an open-label, multinational, 10-year prospective study in clinical practice settings.
  
  
  RESULTS
  In this 5-year interim analysis, 4821 patients were enrolled. Follow-up for at least 4 years from natalizumab commencement in 468 patients and at least 2 years in 2496 patients revealed no new safety signals. There were 18 cases of progressive multifocal leucoencephalopathy reported, following 11-44 natalizumab infusions. Mean annualised relapse rate decreased from 1.99 in the 12 months prior to baseline to 0.31 on natalizumab therapy (p<0.0001), remaining low at 5 years. Lower annualised relapse rates were observed in patients who used natalizumab as first MS therapy, in patients with lower baseline EDSS scores, and in patients with lower prenatalizumab relapse rates. Mean EDSS scores remained unchanged up to 5 years.
  
  
  CONCLUSIONS
  Interim TOP data confirm natalizumab's overall safety profile and the low relapse rate and stabilised disability levels in natalizumab-treated patients with RRMS in clinical practice.
  
  
  BACKGROUND
  NCT00493298.
authors.affiliation: Department of Medicine, Melbourne Brain Centre at the Royal Melbourne Hospital, University of Melbourne, Melbourne, Victoria, Australia Department of Neurology, Box Hill Hospital, Monash University, Victoria, Victoria, Australia.
authors.forename: Helmut
authors.initials: H
authors.lastname: Butzkueven
authors.affiliation: Departments of Neurology and Biomedicine, University Hospital Basel, Basel, Switzerland.
authors.forename: Ludwig
authors.initials: L
authors.lastname: Kappos
authors.affiliation: Department of Clinical Pharmacology and Epidemiology, Consorzio Mario Negri Sud, Chieti, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Pellegrini
authors.affiliation: Department of Neuroscience and Sense Organs, University of Bari, Bari, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Trojano
authors.affiliation: Department of Neurology-Inflammatory Disorders of the Nervous System and Neurooncology, University of Münster, Münster, Germany.
authors.forename: Heinz
authors.initials: H
authors.lastname: Wiendl
authors.affiliation: Biogen Idec Inc, Cambridge, Massachusetts, USA.
authors.forename: Radhika N
authors.initials: RN
authors.lastname: Patel
authors.affiliation: Biogen Idec Inc, Cambridge, Massachusetts, USA.
authors.forename: Annie
authors.initials: A
authors.lastname: Zhang
authors.affiliation: Biogen Idec Inc, Cambridge, Massachusetts, USA.
authors.forename: Christophe
authors.initials: C
authors.lastname: Hotermans
authors.affiliation: Biogen Idec Inc, Cambridge, Massachusetts, USA.
authors.forename: Shibeshih
authors.initials: S
authors.lastname: Belachew
mesh_terms: D000328:Adult; D005260:Female; D006801:Humans; D008297:Male; D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects / Q000627:therapeutic use; D039441:Integrin alpha4 / Q000187:drug effects; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000188:drug therapy; D000069442:Natalizumab; D012008:Recurrence; D012720:Severity of Illness Index; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D039441:Integrin alpha4; D000069442:Natalizumab
keywords: Multiple Sclerosis