Department of Neuroscience, Central Clinical School, Alfred Campus, Monash University, Melbourne, Victoria, Australia.
Neurologic Clinic and Policlinic, Departments of Medicine, Clinical Research, Biomedicine and Biomedical Engineering, University Hospital and University of Basel, Basel, Switzerland.
J Neurol Neurosurg Psychiatry. 2020 Jun;91(6):660-668. doi: 10.1136/jnnp-2019-322326. Epub 2020 Mar 31.
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.
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.
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.
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.
NCT00493298.
Tysabri 观察计划（TOP）开始于 10 多年前，是一项开放性、多国、前瞻性观察性研究，评估那他珠单抗治疗复发缓解型多发性硬化症患者的长期安全性和有效性。
这些数据提供了 TOP 的 10 年中期安全性和有效性分析。采用泊松模型和 Kaplan-Meier 法分别分析年复发率（ARR）和残疾进展/改善。分析包括接受那他珠单抗治疗的患者和停止那他珠单抗但仍留在 TOP 的患者。
截至 2017 年 11 月，TOP 纳入了 6148 例患者。总体而言，829 例患者（13.5%）经历了≥1 次严重不良事件（SAE），感染最常见（4.1%）。53 例患者（0.9%）发生了确诊的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特征一致；未发现新的安全性信号。共有 3210 例患者（52.2%）停止使用那他珠单抗；2117 例（34.4%）退出 TOP。那他珠单抗中位治疗时间为 3.3 年（范围 0-11.6 年）；中位随访时间为 5.2 年（范围 0-10.8 年）。那他珠单抗治疗的 ARR 为 0.15，与起始前相比降低了 92.5%。10 年累积残疾恶化和改善的概率分别为 27.8%和 33.1%。停止或继续使用那他珠单抗的患者的 ARR 相似，表明有限的失访偏倚。
自 TOP 5 年中期分析（2012 年 12 月）以来，队列规模（6148 例比 4821 例）、中位暴露时间（3.3 年比 1.8 年）和中位随访时间（62 个月比 26 个月）均增加。这项 10 年中期分析进一步支持那他珠单抗在现实世界中的强大有效性和已确立的安全性。
NCT00493298。
