[随机双盲安慰剂对照临床试验BCD-132-4/MIRANTIBUS中antid20单克隆抗体divozilimab治疗多发性硬化症患者48周的疗效和安全性]。

Q3 Medicine
A N Boyko, V M Alifirova, I G Lukashevich, Z A Goncharova, I V Greshnova, L G Zaslavsky, S V Kotov, N A Malkova, G N Mishin, E V Parshina, I Ye Poverennova, L N Prakhova, S A Sivertseva, I V Smagina, N A Totolyan, Yu V Trinitatsky, T N Trushnikova, F A Khabirov, J Yu Chefranova, S G Shchur, V A Dudin, D V Pokhabov, D D Bolsun, A V Eremeeva, Yu N Linkova, A V Zinkina-Orikhan
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引用次数: 0

摘要

目的:评价抗cd20单克隆抗体divozilimab (DIV)静脉滴注剂量为500mg治疗复发-缓解型多发性硬化症(RRMS)患者的疗效和安全性,并与teriflunomide (TRF)进行比较。在48周的治疗中,对DIV的疗效和安全性进行了研究。材料与方法:多中心、随机、双盲、双屏蔽III期临床试验(CT) BCD-132-4/MIRANTIBUS纳入338例成年RRMS患者,按1:1比例分为两组:DIV 500 mg和TRF 14 mg。筛选后,受试者进入主CT期,主CT期包括两个治疗周期,为期48周。主要终点是“最后一位患者随机纳入研究后48周的平均年化复发率”。结果:321名受试者按照研究方案完成了48周的治疗。对主要终点疗效数据的分析,相继证明了500mg剂量的试验药物DIV优于对照药物TRF的假设。RRMS患者首次输注DIV后,根据脑MRI和疾病临床表现显示急性疾病活动迅速抑制。因此,接受DIV治疗的患者在治疗48周后,没有T1钆增强病变,而在TRF组中,20.7%(35/169)的受试者观察到这种病变。每次扫描的CUA评估显示,与TRF组相比,DIV组估计期间的平均值有统计学意义显著降低:调整后的每次扫描率(DIV/TRF)之比为0.125 [95% CI: 0.089;0.177]。在48周的治疗中,DIV组的复发比例为9.5% (n=16/169), TRF组的复发比例为19.5% (33/169)(p=0.0086)。DIV已显示出良好的安全性。在不良反应(AR)中,最常记录的是输液反应和实验室数据偏差,如白细胞、中性粒细胞和淋巴细胞数量减少。确定的AR是预期的,有轻度到中度的严重程度,并且没有任何负面后果。结论:与TRF相比,DIV具有较高的疗效和安全性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
[Efficacy and safety of antiCD20 monoclonal antibody divozilimab during 48-week treatment of multiple sclerosis patients in randomized double-blind placebo-controlled clinical trial BCD-132-4/MIRANTIBUS].

Objective: To evaluate the efficacy and safety of the anti-CD20 monoclonal antibody divozilimab (DIV) used as an intravenous infusion at a dose of 500 mg for the treatment of patients with relapsing-remitting multiple sclerosis (RRMS) in comparison with the teriflunomide (TRF). The study of the efficacy and safety of the use of the drug DIV was carried out for 48 weeks of therapy.

Material and methods: The multicenter, randomized, double-blind and double-masked phase III clinical trial (CT) BCD-132-4/MIRANTIBUS included 338 adult patients with RRMS distributed in a 1:1 ratio into two groups: DIV 500 mg and TRF 14 mg. After screening, subjects were included in the main CT period, which consisted of two cycles of therapy over 48 weeks. The primary end point was «Mean annualized relapse rate 48 weeks after the last patient is randomized in the study».

Results: 321 subjects completed 48 weeks of therapy according to the study protocol. The analysis of the of efficacy data for the primary endpoint successively proved the hypothesis of superiority of the test drug DIV at a dose of 500 mg over the reference drug TRF. A rapid suppression of acute disease activity according to the brain MRI and clinical manifestations of the disease was shown after the first infusion of DIV in patients with RRMS. Thus, after 48 weeks of therapy in patients treated with DIV, there were no T1 gadolinium-enhancing lesions, while in the TRF group such lesions were observed in 20.7% (35/169) of subjects. Evaluation of the CUA per scan showed that the mean values for the estimated period were statistically significantly lower in the DIV drug group compared to the TRF group: the ratio of the adjusted per scan rates (DIV/TRF) was 0.125 [95% CI: 0.089; 0.177]. Over the 48 weeks of therapy, the proportion of subjects with relapses was 9.5% (n=16/169) in the DIV group and 19.5% (33/169) in the TRF group (p=0.0086). DIV has shown a favorable safety profile. Among the adverse reactions (AR), infusion reactions and deviations of laboratory data, such as a decrease in the number of leukocytes, neutrophils, and lymphocytes, were most often recorded. Identified AR were expected, had mild to moderate severity, and resolved without any negative consequences.

Conclusion: The results of the clinical study indicate the high efficacy and safety of DIV in comparison with TRF.

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来源期刊
Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova
Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova Medicine-Psychiatry and Mental Health
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