Tysabri Observational Program (TOP): long-term safety and effectiveness of natalizumab treatment in relapsing-remitting multiple sclerosis over 15 years.
Helmut Butzkueven, Ludwig Kappos, Heinz Wiendl, Maria Trojano, Tim Spelman, Andres Greco, Zhaonan Sun, Tyler Lasky
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引用次数: 0
Abstract
Objective: This Tysabri Observational Program (TOP) final analysis evaluated the 15-year safety and effectiveness of natalizumab treatment in patients with relapsing-remitting multiple sclerosis (RRMS).
Methods: This multinational, real-world observational study assessed natalizumab-associated serious adverse events, annualised relapse rates (ARRs) and disability progression/improvement in patients with RRMS. These outcomes were evaluated in subpopulations receiving short- (1-2 years) versus long-term (≥10 years) natalizumab and in patients who switched from intravenous to subcutaneous (SC) natalizumab formulation. The probability of conversion to non-active secondary progressive multiple sclerosis (SPMS) was assessed in patients who remained on versus discontinued natalizumab after ≥1 year.
Results: As of November 2023, TOP enrolled 6319 patients. Median time on natalizumab was 4.13 years. There were no new safety signals after up to 15 years of treatment. Marked, sustained reductions in pretreatment ARR occurred with natalizumab independent of baseline disease indicators (eg, Expanded Disability Status Scale score). On natalizumab, the ARR decreased by 91.5% after 15 years, relative to the year before baseline. At 15.5 years, cumulative probabilities of 24-week confirmed disability progression and improvement were 48.5% and 38.8%, respectively. Long-term natalizumab treatment significantly decreased ARR compared with short-term treatment. Switching from intravenous to SC formulation did not affect ARR after 1 year post-switch. The cumulative probability of converting to non-active SPMS was significantly lower in patients remaining on natalizumab compared with those who discontinued (0.22 vs 0.29, respectively).
Conclusions: Follow-up of over 15 years did not reveal new safety concerns and confirmed sustained real-world effectiveness of natalizumab in patients with RRMS (NCT00493298).
目的：Tysabri观察项目（TOP）最终分析评估了natalizumab治疗复发-缓解型多发性硬化症（RRMS）患者15年的安全性和有效性。方法：这项跨国、真实世界的观察性研究评估了RRMS患者与natalizumab相关的严重不良事件、年化复发率（arr）和残疾进展/改善。这些结果在接受短期（1-2年）与长期（≥10年）纳他珠单抗的亚群中进行了评估，并在从静脉注射到皮下（SC）纳他珠单抗制剂的患者中进行了评估。在持续使用纳他珠单抗与停用纳他珠单抗≥1年后的患者中，评估了转化为非活动性继发性进行性多发性硬化症（SPMS）的可能性。结果：截至2023年11月，TOP入组6319例患者。natalizumab的中位治疗时间为4.13年。在长达15年的治疗后，没有出现新的安全信号。纳他珠单抗在独立于基线疾病指标（如扩展残疾状态量表评分）的情况下，显著地持续降低了预处理ARR。对于natalizumab，相对于基线前一年，15年后ARR下降了91.5%。在15.5年时，24周确认残疾进展和改善的累积概率分别为48.5%和38.8%。与短期治疗相比，长期纳他珠单抗治疗显著降低ARR。从静脉注射到SC制剂的转换在转换后1年没有影响ARR。与停用natalizumab的患者相比，继续使用natalizumab的患者转化为非活性SPMS的累积概率显著降低（分别为0.22 vs 0.29）。结论：超过15年的随访未发现新的安全性问题，并证实natalizumab对RRMS患者（NCT00493298）的持续实际有效性。
期刊介绍：
The Journal of Neurology, Neurosurgery & Psychiatry (JNNP) aspires to publish groundbreaking and cutting-edge research worldwide. Covering the entire spectrum of neurological sciences, the journal focuses on common disorders like stroke, multiple sclerosis, Parkinson’s disease, epilepsy, peripheral neuropathy, subarachnoid haemorrhage, and neuropsychiatry, while also addressing complex challenges such as ALS. With early online publication, regular podcasts, and an extensive archive collection boasting the longest half-life in clinical neuroscience journals, JNNP aims to be a trailblazer in the field.
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