Internal Medicine, Dow University of Health Sciences, Karachi; Pakistan.
Internal Medicine, Dow University of Health Sciences, Karachi; Pakistan.
Mult Scler Relat Disord. 2022 May;61:103743. doi: 10.1016/j.msard.2022.103743. Epub 2022 Mar 15.
Multiple Sclerosis (MS) is a chronic debilitating neurological disease affecting young adults. The disease involves immune-mediated demyelination of nerve fibers and neurons that leads to disruption of brain-body communication, leading to permanent nerve damage. MS-associated retrovirus envelope protein (MSRV-Env) has been detected in the blood and lesions of MS patients, and its role is suggested in the pathogenesis of MS. Temelimab is a humanized IgG4 monoclonal antibody (mAb) that targets the MSRV-Env protein and neutralizes its action. Several clinical trials have been conducted to evaluate the effectiveness of the drug in MS.
A systemic search was conducted from electronic databases (PubMed/Medline, Cochrane Library, and Google Scholar) from inception to 11th sept 2021. All statistical analysis was conducted in Review Manager 5.4.1. Studies meeting inclusion criteria were selected. Those studies were selected which compared Temelimab therapy to inactive control. The primary outcome of interest was drug safety and efficacy; information about immunogenicity was also included. Random-effect model was used to pool the studies, and the result was reported in the risk ratio (RR) with corresponding 95% Confidence interval (CI).
Phase I, Phase II-a and Phase II-b trials demonstrate the safety and effectiveness of Temelimab. Our analysis showed statistically non-significant Risk Ratio (RR) of Adverse events in Temelimab group than that in placebo group (1.01 [0.70,1.46]; p-value = 0.94; I = 0%) . Considering the effect of Temelimab on brain lesions, pooled result showed statistically significant Risk Ratio (RR) of brain lesions in placebo group than that in Temelimab group (0.75 [0.69,0.81), p-value < 0.00001, I = 0% CONCLUSION: Qualitative and quantitative analysis of the trials assessing the safety and efficacy of Temelimab demonstrate that the drug is safe as well as favourable for use in MS patients.
多发性硬化症（MS）是一种影响年轻人的慢性衰弱性神经系统疾病。该疾病涉及到神经纤维和神经元的免疫介导脱髓鞘，导致脑-体通讯中断，导致永久性神经损伤。已在 MS 患者的血液和病变中检测到与多发性硬化症相关的逆转录病毒包膜蛋白（MSRV-Env），其在 MS 的发病机制中起作用。Temelimab 是一种靶向 MSRV-Env 蛋白并中和其作用的人源化 IgG4 单克隆抗体（mAb）。已经进行了几项临床试验来评估该药物在 MS 中的疗效。
从电子数据库（PubMed/Medline、Cochrane 图书馆和 Google Scholar）进行系统搜索，从开始到 2021 年 9 月 11 日。所有统计分析均在 Review Manager 5.4.1 中进行。选择符合纳入标准的研究。选择了将 Temelimab 治疗与安慰剂对照进行比较的研究。主要研究结果是药物安全性和疗效；还包括免疫原性信息。使用随机效应模型对研究进行合并，并以风险比（RR）及其相应的 95%置信区间（CI）报告结果。
I 期、IIa 期和 IIb 期试验证明 Temelimab 的安全性和有效性。我们的分析显示 Temelimab 组与安慰剂组不良事件的风险比（RR）无统计学意义（1.01 [0.70,1.46]；p 值=0.94；I=0%）。考虑到 Temelimab 对脑病变的影响，合并结果显示安慰剂组脑病变的风险比（RR）明显低于 Temelimab 组（0.75 [0.69,0.81），p 值<0.00001，I=0%）。
评估 Temelimab 安全性和疗效的试验的定性和定量分析表明，该药物既安全又有利于 MS 患者使用。
