尼森仑赛治疗成人脊髓性肌萎缩症：实验室参数的安全性分析。
Nusinersen treatment in adult patients with spinal muscular atrophy: a safety analysis of laboratory parameters.
机构信息
Department of Neurology, University Hospital Essen, Hufelandstr. 55, 45147, Essen, Germany.
Center for Translational and Behavioral Neuroscience, University Hospital Essen, Essen, Germany.
出版信息
J Neurol. 2021 Dec;268(12):4667-4679. doi: 10.1007/s00415-021-10569-8. Epub 2021 Apr 25.
BACKGROUND
Nusinersen is an intrathecally administered antisense oligonucleotide (ASO) that improves motor function in patients with spinal muscular atrophy (SMA). In addition to efficacy, the safety of a therapy is the decisive factor for the success of the treatment. For some ASOs, various organ toxicities have been described, such as thrombocytopenia, renal and liver impairment, or coagulation abnormalities. However, systematic data on laboratory parameters under treatment with nusinersen are mainly available from studies in infants and children. Therefore, our aim was to assess the safety of nusinersen therapy in adult SMA patients.
METHODS
Laboratory data from 404 nusinersen injections performed in 50 adult patients with SMA type 2 and type 3 were retrospectively analyzed.
RESULTS
The total observation period was 76.9 patient-years, and patients received up to 12 injections. Our data provides no new safety concerns. In cerebrospinal fluid (CSF), the mean white blood cell count and lactate remained stable over time. Total CSF protein increased by 2.9 mg/dL. No change in mean platelet count was observed under therapy. Only one patient showed sporadic mild thrombocytopenia. Coagulation parameters and inflammatory markers were stable. The mean creatinine level decreased by 0.09 mg/dL. Analysis of mean liver enzyme levels revealed no relevant changes during treatment.
CONCLUSION
Our data demonstrate a favorable safety profile of nusinersen therapy in adult SMA patients under longer-term "real-world" conditions. In particular, we found no evidence of clinically relevant platelet declines, coagulopathies, or renal or hepatic organ toxicities, which are common concerns with the use of ASOs.
背景
Nusinersen 是一种鞘内给药的反义寡核苷酸（ASO），可改善脊髓性肌萎缩症（SMA）患者的运动功能。除了疗效外，治疗的安全性是治疗成功的决定性因素。对于某些 ASO，已经描述了各种器官毒性，例如血小板减少症、肾和肝损伤或凝血异常。然而，关于用 nusinersen 治疗的实验室参数的系统数据主要来自婴儿和儿童的研究。因此，我们的目的是评估 nusinersen 治疗成人 SMA 患者的安全性。
方法
回顾性分析了 50 例 2 型和 3 型 SMA 成年患者的 404 次 nusinersen 注射的实验室数据。
结果
总观察期为 76.9 患者年，患者接受了多达 12 次注射。我们的数据没有提供新的安全性问题。在脑脊液（CSF）中，白细胞计数和乳酸的平均值随时间保持稳定。总 CSF 蛋白增加了 2.9mg/dL。治疗期间血小板计数无明显变化。只有一名患者出现散发性轻度血小板减少症。凝血参数和炎症标志物稳定。平均肌酐水平下降 0.09mg/dL。分析平均肝酶水平显示治疗期间无明显变化。
结论
我们的数据表明，在长期“真实世界”条件下，nusinersen 治疗成人 SMA 患者的安全性良好。特别是，我们没有发现临床上相关的血小板下降、凝血障碍或肾或肝器官毒性的证据，这些是使用 ASO 的常见关注点。
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