Clinical effects of natalizumab on multiple sclerosis appear early in treatment course.
Clinical effects of natalizumab on multiple sclerosis appear early in treatment course.
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DOI：
10.1007/s00415-012-6809-7
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发表时间：
2013-05
影响因子：
6
通讯作者：
Hotermans C
中科院分区：
文献类型：
--
作者：
Kappos L;O'Connor PW;Polman CH;Vermersch P;Wiendl H;Pace A;Zhang A;Hotermans C
在临床实践中，natalizumab通常用于在干扰素β (IFNβ)或醋酸格拉替雷默治疗期间经历突破性疾病的患者。在这些患者中，重要的是尽快减少疾病活动。在一项II期研究中，natalizumab和安慰剂在第一次输注后反映炎症活动的MRI结果的差异很明显，并维持了6个月的时间，这表明natalizumab治疗效果的快速起效。为了探索natalizumab启动临床效果多长时间变得明显，在III期AFFIRM研究（natalizumab与安慰剂）和跨国Tysabri®观察项目（TOP）中分析了每3个月的年化复发率和首次复发时间。在AFFIRM中，与安慰剂相比，natalizumab在总体人群（0.30 vs. 0.71, p < 0.0001）和疾病高度活跃的患者（0.30 vs. 0.94, p = 0.0039）中降低了治疗开始后3个月内的年化复发率。在整个2年的研究期间，维持了较低的年化复发率，并且接受natalizumab治疗的AFFIRM患者的复发风险降低[与安慰剂相比的风险比为0.42 (95% CI 0.34-0.52)；p < 0.0001]。TOP患者的年复发率也迅速下降（基线1.99 vs. 0-3个月0.26;p < 0.0001）。Natalizumab在AFFIRM和临床实践中都能快速、持续地降低疾病活动性。这种疾病活动性的下降发生在治疗的前3个月内，即使是在疾病更活跃的患者中。
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.
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