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

被引:41
作者
Kappos, Ludwig [1 ,2 ]
O'Connor, Paul W. [3 ]
Polman, Christopher H. [4 ]
Vermersch, Patrick [5 ]
Wiendl, Heinz [6 ]
Pace, Amy [7 ]
Zhang, Annie [7 ]
Hotermans, Christophe [7 ]
机构
[1] Univ Basel Hosp, Dept Neurol, CH-4031 Basel, Switzerland
[2] Univ Basel Hosp, Dept Biomed, CH-4031 Basel, Switzerland
[3] St Michaels Hosp, MS Clin, Toronto, ON M5B 1W8, Canada
[4] Vrije Univ Amsterdam Med Ctr, NL-1007 MB Amsterdam, Netherlands
[5] Univ Lille Nord France, Dept Neurol, Clin Neurol, Hop Roger Salengro,CHU Lille, F-59037 Lille, France
[6] Univ Munster, Dept Neurol Inflammatory Dis Nervous Syst & Neuro, Neurol Clin, D-48149 Munster, Germany
[7] Biogen Idec Inc, Weston, MA 02493 USA
基金
新加坡国家研究基金会;
关键词
Multiple sclerosis; Natalizumab; Relapse; Disease activity; Disease-modifying therapy; Annualized relapse rate; PLACEBO-CONTROLLED TRIAL; HIGH DISEASE-ACTIVITY; INTEGRIN ANTIBODY; DISABILITY STATUS; ORAL FINGOLIMOD; EFFICACY; MULTICENTER; IMPROVEMENT; RATIONALE; THERAPY;
D O I
10.1007/s00415-012-6809-7
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
In clinical practice natalizumab is typically used in patients who have experienced breakthrough disease during treatment with interferon beta (IFN beta) 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(A (R)) 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.
引用
收藏
页码:1388 / 1395
页数:8
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