Original Communication

Journal of Neurology

, Volume 260, Issue 5, pp 1388-1395

First online:

Open Access This content is freely available online to anyone, anywhere at any time.

Clinical effects of natalizumab on multiple sclerosis appear early in treatment course

  • Ludwig KapposAffiliated withDepartments of Neurology and Biomedicine, University Hospital Basel Email author 
  • , Paul W. O’ConnorAffiliated withMS Clinic, St. Michael’s Hospital
  • , Christopher H. PolmanAffiliated withVU Medical Centre
  • , Patrick VermerschAffiliated withDepartment of Neurology, Clinique neurologique, Hôpital Roger Salengro, University of Lille Nord de France
  • , Heinz WiendlAffiliated withDepartment of Neurology-Inflammatory Diseases of the Nervous System and Neurooncology, Neurology Clinic, University of Münster
  • , Amy PaceAffiliated withBiogen Idec Inc.
  • , Annie ZhangAffiliated withBiogen Idec Inc.
  • , Christophe HotermansAffiliated withBiogen Idec Inc.


In clinical practice natalizumab is typically used in patients who have experienced breakthrough disease during treatment with interferon beta (IFNβ) or glatiramer acetate. In these patients it is important to reduce disease activity as quickly as possible. In a phase II study, differences between natalizumab and placebo in MRI outcomes reflecting inflammatory activity were evident after the first infusion and maintained through a 6-month period, suggesting a rapid onset of natalizumab treatment effects. To explore how soon after natalizumab initiation clinical effects become apparent, annualized relapse rates per 3-month period and time to first relapse were analyzed in the phase III AFFIRM study (natalizumab vs. placebo) and in the multinational Tysabri® Observational Program (TOP). In AFFIRM, natalizumab reduced the annualized relapse rate within 3 months of treatment initiation compared with placebo in the overall population (0.30 vs. 0.71; p < 0.0001) and in patients with highly active disease (0.30 vs. 0.94; p = 0.0039). The low annualized relapse rate was maintained throughout the 2-year study period, and the risk of relapse in AFFIRM patients treated with natalizumab was reduced [hazard ratio against placebo 0.42 (95 % CI 0.34–0.52); p < 0.0001]. Rapid reductions in annualized relapse rate also occurred in TOP (baseline 1.99 vs. 0–3 months 0.26; p < 0.0001). Natalizumab resulted in rapid, sustained reductions in disease activity in both AFFIRM and in clinical practice. This decrease in disease activity occurred within the first 3 months of treatment even in patients with more active disease.


Multiple sclerosis Natalizumab Relapse Disease activity Disease-modifying therapy Annualized relapse rate