评估西尼莫德治疗患者对SARS-CoV-2 mRNA疫苗的免疫反应：一项非随机对照临床试验（AMA-VACC）。
Assessing the immune response to SARS-CoV-2 mRNA vaccines in siponimod-treated patients: a nonrandomized controlled clinical trial (AMA-VACC).
作者信息
Ziemssen Tjalf, Groth Marie, Rauser Benedict, Bopp Tobias
机构信息
Department of Neurology, Center of Clinical Neuroscience, Carl Gustav Carus University Clinic, University Hospital of Dresden, Fetscherstraße 74, 01307 Dresden, Germany.
Novartis Pharma GmbH, Nuremberg, Germany.
出版信息
Ther Adv Neurol Disord. 2022 Nov 8;15:17562864221135305. doi: 10.1177/17562864221135305. eCollection 2022.
BACKGROUND
Systematic data are lacking on the immune response toward SARS-CoV-2 mRNA vaccination in SPMS patients on disease-modifying therapies (DMTs).
OBJECTIVE
The AMA-VACC clinical trial was designed to characterize immune responses to SARS-CoV-2 mRNA vaccines in siponimod-treated SPMS patients.
DESIGN
AMA-VACC is an ongoing three-cohort, multicenter, open-label, prospective clinical study.
METHODS
The study included patients at risk for SPMS or patients with SPMS diagnosis. Patients received SARS-CoV-2 mRNA vaccine as part of their clinical routine during ongoing siponimod treatment (cohort 1), during siponimod treatment interruption (cohort 2), or while on dimethyl fumarate, glatiramer acetate, beta-interferons, teriflunomide, or no current therapy (cohort 3). SARS-CoV-2-specific neutralizing antibodies and T-cell responses were measured 1 week and 1 month after the second dose of vaccination.
RESULTS
In total, 17 patients, 4 patients, and 20 patients were recruited into cohorts 1, 2, and 3, respectively. The primary endpoint of seroconversion for SARS-CoV-2-neutralizing antibodies at week 1 was reached by 52.9%, 75.0%, and 90.0% of patients in cohorts 1, 2, and 3, respectively. For 64.7% of patients in cohort 1, all patients in cohort 2, and 95% of patients in cohort 3, seroconversion was observed at either week 1 or month 1 or both time points. After 1 week, 71.4% of cohort 1, 75.0% of cohort 2, and 85.0% of cohort 3 were positive for either SARS-CoV-2-neutralizing antibodies or SARS-CoV-2-specific T-cells or both. After 1 month, the rates were 56.3%, 100.0%, and 95.0%, respectively.
CONCLUSION
The study shows that the majority of siponimod patients mount humoral and cellular immune response under continuous siponimod treatment. The data do not sufficiently support interruption of treatment for the purpose of vaccination.
REGISTRATION
EU Clinical Trials Register: EudraCT 2020-005752-38 (www.clinicaltrialsregister.eu); ClinicalTrials.gov: NCT04792567 (https://clinicaltrials.gov).
背景
缺乏关于接受疾病修饰治疗（DMTs）的继发进展型多发性硬化（SPMS）患者对SARS-CoV-2 mRNA疫苗免疫反应的系统性数据。
目的
AMA-VACC临床试验旨在描述西尼莫德治疗的SPMS患者对SARS-CoV-2 mRNA疫苗的免疫反应。
设计
AMA-VACC是一项正在进行的三队列、多中心、开放标签的前瞻性临床研究。
方法
该研究纳入有SPMS风险的患者或已确诊SPMS的患者。患者在持续接受西尼莫德治疗期间（队列1）、西尼莫德治疗中断期间（队列2）或接受富马酸二甲酯、醋酸格拉替雷、β-干扰素、特立氟胺治疗期间或未接受当前治疗时（队列3），将SARS-CoV-2 mRNA疫苗作为其临床常规治疗的一部分接种。在接种第二剂疫苗后1周和1个月测量SARS-CoV-2特异性中和抗体和T细胞反应。
结果
分别有17例、4例和20例患者被纳入队列1、队列2和队列3。队列1、队列2和队列3中分别有52.9%、75.0%和90.0%的患者在第1周达到SARS-CoV-2中和抗体血清转化的主要终点。队列1中64.7%的患者、队列2中的所有患者以及队列3中95%的患者在第1周或第1个月或两个时间点均观察到血清转化。1周后，队列1中71.4%、队列2中75.0%和队列3中85.0%的患者SARS-CoV-2中和抗体或SARS-CoV-2特异性T细胞或两者均呈阳性。1个月后，相应比例分别为56.3%、100.0%和95.0%。
结论
该研究表明，大多数西尼莫德治疗的患者在持续接受西尼莫德治疗的情况下产生体液免疫和细胞免疫反应。这些数据不足以支持为了接种疫苗而中断治疗。
注册信息
欧盟临床试验注册库：EudraCT 2020-005752-38（www.clinicaltrialsregister.eu）；美国国立医学图书馆临床试验数据库：NCT04792567（https://clinicaltrials.gov）。
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