Article Text

Research paper
Efficacy and safety of natalizumab in multiple sclerosis: interim observational programme results
  1. Helmut Butzkueven1,2,
  2. Ludwig Kappos3,
  3. Fabio Pellegrini4,
  4. Maria Trojano5,
  5. Heinz Wiendl6,
  6. Radhika N Patel7,
  7. Annie Zhang7,
  8. Christophe Hotermans7,
  9. Shibeshih Belachew7
  10. on behalf of the TYSABRI Observational Program (TOP) Investigators
  1. 1Department of Medicine, Melbourne Brain Centre at the Royal Melbourne Hospital, University of Melbourne, Melbourne, Victoria, Australia
  2. 2Department of Neurology, Box Hill Hospital, Monash University, Victoria, Victoria, Australia
  3. 3Departments of Neurology and Biomedicine, University Hospital Basel, Basel, Switzerland
  4. 4Department of Clinical Pharmacology and Epidemiology, Consorzio Mario Negri Sud, Chieti, Italy
  5. 5Department of Neuroscience and Sense Organs, University of Bari, Bari, Italy
  6. 6Department of Neurology–Inflammatory Disorders of the Nervous System and Neurooncology, University of Münster, Münster, Germany
  7. 7Biogen Idec Inc, Cambridge, Massachusetts, USA
  1. Correspondence to Dr H Butzkueven, Department of Medicine, Royal Melbourne Hospital Brain Centre, University of Melbourne, Level 4 East, Royal Melbourne Hospital Campus, Grattan Street, Parkville, Melbourne, VIC 3050, Australia; butz{at}


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.

Trial registration number NCT00493298.

  • Multiple Sclerosis

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