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那他珠单抗实现无疾病活动证据(NEDA-3)的有效性——来自挪威本地队列的数据

Effectiveness of Natalizumab in Achieving No Evidence of Disease Activity (NEDA-3)-Data From a Local Norwegian Cohort.

作者信息

Jaklin Andreas K, Benjaminsen Espen, Alstadhaug Karl B

机构信息

Department of Medicine, University Hospital of North Norway, Tromsø, Norway.

Department of Neurology, Nordland Hospital Trust, Bodø, Norway.

出版信息

Front Neurol. 2021 Oct 20;12:765837. doi: 10.3389/fneur.2021.765837. eCollection 2021.

Abstract

We aimed to determine the effectiveness of natalizumab (NTZ) by assessing overall No Evidence of Disease Activity 3 (NEDA-3) in a local Norwegian cohort. NTZ is an immunomodulating drug used in the treatment of multiple sclerosis (MS). It has typically been used as a second-line treatment, but certain patients with high disease activity have started directly with NTZ. This retrospective cohort study includes all patients who received NTZ for relapsing-remitting MS at Nordland Hospital in the period 2008-2018. In June 2019, status for every patient was assessed, and a survival curve was used to show the cumulative probability of achieving NEDA-3 over time. The cohort consisted of 66 patients, 49 women and 17 men with a mean age of 40.0 ± 10.8 years. Each patient received on average 45.8 ± 36.4 NTZ infusions. Mean age and Expanded Disability Status Scale (EDSS) at first infusion was 34.8 ± 10.5 and 3.2 ± 1.9, respectively. Prior to NTZ treatment, 83% had used other disease modulating drugs and 65% were anti-JC virus (JCV) seronegative. During the study period, seven patients converted to seropositive. In 2019, 40 patients had switched or stopped treatment: 19 due to positive JCV serostatus, 9 due to disease activity, 7 due to adverse effects or complications (1 progressive multifocal leukoencephalopathy), 2 due to pregnancy, and 3 due to autologous hematopoietic cell transplantation abroad. Three patients experienced rebound in the wake of discontinuation (7.5%). Of the patients receiving NTZ for more than 3 years ( = 33), 50% had achieved NEDA-3 after 3 years. Compared to those with evidence of disease activity (EDA), these NEDA-3 patients had significant lower EDSS score before first NTZ treatment ( = 0.04). They were also slightly, but not significantly, younger at debut of their MS, at the diagnosis and at first NTZ treatment. Of all the patients who ever started on NTZ, 23% had achieved NEDA-3 5 years later. The mean EDSS in 2019 was 3.6 ± 2.5. Despite the high rate of treatment switch, mainly due to the risk of PML, almost one in four who started on NTZ achieved NEDA-3 after 5 years, and the overall disease progression was low in the total cohort. Treating less advanced disease seems to predict better long-term stability.

摘要

我们旨在通过评估挪威当地队列中无疾病活动证据3(NEDA-3)的总体情况来确定那他珠单抗(NTZ)的有效性。NTZ是一种用于治疗多发性硬化症(MS)的免疫调节药物。它通常被用作二线治疗,但某些疾病活动度高的患者已直接开始使用NTZ。这项回顾性队列研究纳入了2008年至2018年期间在诺尔兰医院接受NTZ治疗复发缓解型MS的所有患者。2019年6月,对每位患者的病情进行了评估,并使用生存曲线来显示随时间实现NEDA-3的累积概率。该队列由66名患者组成,其中49名女性和17名男性,平均年龄为40.0±10.8岁。每位患者平均接受了45.8±36.4次NTZ输注。首次输注时的平均年龄和扩展残疾状态量表(EDSS)分别为34.8±10.5和3.2±1.9。在接受NTZ治疗之前,83%的患者曾使用过其他疾病调节药物,65%的患者抗JC病毒(JCV)血清学阴性。在研究期间,7名患者血清学转为阳性。2019年,40名患者已换药或停药:19名因JCV血清学阳性,9名因疾病活动,7名因不良反应或并发症(1例进行性多灶性白质脑病),2名因怀孕,3名因在国外进行自体造血细胞移植。3名患者在停药后出现病情反弹(7.5%)。在接受NTZ治疗超过3年的患者(n = 33)中,50%在3年后实现了NEDA-3。与有疾病活动证据(EDA)的患者相比,这些NEDA-3患者在首次接受NTZ治疗前的EDSS评分显著更低(P = 0.04)。他们在MS起病、诊断和首次接受NTZ治疗时也略年轻,但差异不显著。在所有开始使用NTZ的患者中,23%在5年后实现了NEDA-3。2019年的平均EDSS为3.6±2.5。尽管换药率很高,主要是由于存在进行性多灶性白质脑病的风险,但开始使用NTZ的患者中几乎四分之一在5年后实现了NEDA-3,并且整个队列中的总体疾病进展较低。治疗病情较轻的疾病似乎预示着更好的长期稳定性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d499/8563783/df8fa2e634e8/fneur-12-765837-g0001.jpg

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