OBJECTIVE The Tysabri Observational Programme (TOP), which began >10 years ago, is an open-label, multinational, prospective observational study evaluating the long-term safety and effectiveness of natalizumab in relapsing-remitting multiple sclerosis patients. METHODS These data provide a 10-year interim analysis of safety and effectiveness in TOP. Annualised relapse rates (ARRs) and disability progression/improvement were analysed using the Poisson model and the Kaplan-Meier method, respectively. Analyses included patients on natalizumab and those who discontinued natalizumab but remained in TOP. RESULTS As of November 2017, TOP included 6148 patients. Overall, 829 patients (13.5%) experienced ≥1 serious adverse event (SAE), with infection the most common (4.1%). Fifty-three patients (0.9%) had confirmed progressive multifocal leukoencephalopathy. SAE data were consistent with natalizumab's known safety profile; no new safety signals were identified. A total of 3210 patients (52.2%) discontinued natalizumab; 2117 (34.4%) withdrew from TOP. Median time on natalizumab was 3.3 (range 0-11.6) years; median follow-up time was 5.2 (range 0-10.8) years. The on-natalizumab ARR was 0.15, a 92.5% reduction from the year before initiation. Ten-year cumulative probabilities of disability worsening and improvement were 27.8% and 33.1%, respectively. On-natalizumab ARRs were similar between patients who discontinued or remained on natalizumab, suggesting limited attrition bias. CONCLUSIONS Since the TOP 5-year interim analysis (December 2012), cohort size (6148 vs 4821), median exposure (3.3 vs 1.8 years) and median follow-up time (62 vs 26 months) have increased. This 10-year interim analysis further supports the robust real-world effectiveness and well-established safety profile of natalizumab. TRIAL REGISTRATION NUMBER NCT00493298.

中文翻译：

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那他珠单抗治疗在临床实践中的长期安全性和有效性：来自Tysabri观察计划（TOP）的10年真实数据。

目的Tysabri观察计划（TOP）始于10年前，是一项开放性，多国性，前瞻性观察研究，评估了那他珠单抗在复发缓解型多发性硬化症患者中的长期安全性和有效性。方法这些数据提供了为期10年的TOP安全性和有效性的中期分析。分别使用Poisson模型和Kaplan-Meier方法分析了年度复发率（ARR）和残疾进展/改善情况。分析包括接受那他珠单抗治疗的患者和那些停止那他珠单抗治疗但仍在TOP治疗的患者。结果截至2017年11月，TOP包括6148名患者。总体而言，有829例患者（13.5％）经历了≥1个严重不良事件（SAE），其中感染最为常见（4.1％）。五十三名患者（0。9％）已确认进行性多灶性白质脑病。SAE数据与那他珠单抗已知的安全性一致；没有发现新的安全信号。共有3210例患者（52.2％）停用那他珠单抗；2117（34.4％）从最高处退出。那他珠单抗的中位时间为3.3（0-11.6）年；中位随访时间为5.2（0-10.8）年。那他珠单抗的ARR为0.15，比开始治疗前的那一年降低了92.5％。十年残疾累积和改善的累计概率分别为27.8％和33.1％。停用或继续使用那他珠单抗的患者之间的那他珠单抗的ARR相似，表明减员偏倚有限。结论自从前5年期中期分析（2012年12月）以来，队列规模（6148对4821），中位数暴露（3.3对1。8年）和中位随访时间（62对26个月）有所增加。这项为期10年的中期分析进一步支持了那他珠单抗在现实世界中的稳健有效性和公认的安全性。试用注册号NCT00493298。