title: Clinical effects of natalizumab on multiple sclerosis appear early in treatment course.
abstract: 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.
authors.affiliation: Departments of Neurology and Biomedicine, University Hospital Basel, Petersgraben 4, Basel, Switzerland. lkappos@uhbs.ch
authors.forename: Ludwig
authors.initials: L
authors.lastname: Kappos
authors.forename: Paul W
authors.initials: PW
authors.lastname: O'Connor
authors.forename: Christopher H
authors.initials: CH
authors.lastname: Polman
authors.forename: Patrick
authors.initials: P
authors.lastname: Vermersch
authors.forename: Heinz
authors.initials: H
authors.lastname: Wiendl
authors.forename: Amy
authors.initials: A
authors.lastname: Pace
authors.forename: Annie
authors.initials: A
authors.lastname: Zhang
authors.forename: Christophe
authors.initials: C
authors.lastname: Hotermans
mesh_terms: D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D004185:Disability Evaluation; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use*; D016899:Interferon-beta / Q000276:immunology*; D007391:International Cooperation; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D008297:Male; D009103:Multiple Sclerosis / Q000188:drug therapy*; D000069442:Natalizumab; D055502:Secondary Prevention; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D007155:Immunologic Factors; D000069442:Natalizumab; D016899:Interferon-beta