Abstract：
Type 1 diabetes mellitus is widely recognized as a chronic autoimmune disease characterized by the pathogenic destruction of beta cells, resulting in the loss of endogenous insulin production. Insulin administration remains the primary therapy for symptomatic treatment. Recent studies showed that disease-modifying agents, such as anti-CD3 monoclonal antibodies, have shown promising outcomes in improving the management of the disease. In late 2022, teplizumab received approval from the US Food and Drug Administration (FDA) as the first disease-modifying agent for the treatment of type 1 diabetes. This review aims to evaluate the clinical evidence regarding the efficacy of anti-CD3 monoclonal antibodies in the prevention and treatment of type 1 diabetes.
A comprehensive search of PubMed, Google Scholar, Scopus and Cochrane Central Register of Controlled Trials (CENTRAL) was conducted up to December 2022 to identify relevant randomized controlled trials. Meta-analysis was performed using a random-effects model, and odds ratios with 95% confidence intervals (CIs) were calculated to quantify the effects. The Cochrane risk of bias tool was employed for quality assessment.
In total, 11 randomized controlled trials involving 1397 participants (908 participants in the intervention arm, 489 participants in the control arm) were included in this review. The mean age of participants was 15 years, and the mean follow-up time was 2.04 years. Teplizumab was the most commonly studied intervention. Compared with placebo, anti-CD3 monoclonal antibody treatment significantly increased the C-peptide concentration in the area under the curve at shorter timeframes (mean difference = 0.114, 95% CI: 0.069 to 0.159, p = .000). Furthermore, anti-CD3 monoclonal antibodies significantly reduced the patients\' insulin intake across all timeframes (mean difference = -0.123, 95% CI: -0.151 to -0.094, p < .001). However, no significant effect on glycated haemoglobin concentration was observed.
The findings of this review suggest that anti-CD3 monoclonal antibody treatment increases endogenous insulin production and improves the lifestyle of patients by reducing insulin dosage. Future studies should consider the limitations, including sample size, heterogeneity and duration of follow-up, to validate the generalizability of these findings further.
A comprehensive search of PubMed, Google Scholar, Scopus and Cochrane Central Register of Controlled Trials (CENTRAL) was conducted up to December 2022 to identify relevant randomized controlled trials. Meta-analysis was performed using a random-effects model, and odds ratios with 95% confidence intervals (CIs) were calculated to quantify the effects. The Cochrane risk of bias tool was employed for quality assessment.
In total, 11 randomized controlled trials involving 1397 participants (908 participants in the intervention arm, 489 participants in the control arm) were included in this review. The mean age of participants was 15 years, and the mean follow-up time was 2.04 years. Teplizumab was the most commonly studied intervention. Compared with placebo, anti-CD3 monoclonal antibody treatment significantly increased the C-peptide concentration in the area under the curve at shorter timeframes (mean difference = 0.114, 95% CI: 0.069 to 0.159, p = .000). Furthermore, anti-CD3 monoclonal antibodies significantly reduced the patients\' insulin intake across all timeframes (mean difference = -0.123, 95% CI: -0.151 to -0.094, p < .001). However, no significant effect on glycated haemoglobin concentration was observed.
The findings of this review suggest that anti-CD3 monoclonal antibody treatment increases endogenous insulin production and improves the lifestyle of patients by reducing insulin dosage. Future studies should consider the limitations, including sample size, heterogeneity and duration of follow-up, to validate the generalizability of these findings further.
摘要：
目的：1型糖尿病是一种以β细胞的致病性破坏为特征的慢性自身免疫性疾病，导致内源性胰岛素产生的损失。胰岛素给药仍然是对症治疗的主要疗法。最近的研究表明，疾病调节剂，如抗CD3单克隆抗体，在改善疾病管理方面显示出有希望的结果。2022年末，teplizumab获得了美国食品和药物管理局（FDA）的批准，成为治疗1型糖尿病的第一种疾病调节剂。本文旨在评估抗CD3单克隆抗体在1型糖尿病预防和治疗中的临床证据。
方法：对PubMed的全面搜索，谷歌学者，Scopus和Cochrane中央对照试验注册中心（CENTRAL）于2022年12月进行，以确定相关的随机对照试验。使用随机效应模型进行荟萃分析，计算比值比和95%置信区间(CI)以量化效果。采用Cochrane偏倚风险工具进行质量评估。
结果：总计，11项随机对照试验，涉及1397名参与者(干预组908名参与者，控制臂中的489名参与者)被纳入本综述。参与者的平均年龄是15岁,平均随访时间为2.04年。Teplizumab是最常用的研究干预措施。与安慰剂相比，抗CD3单克隆抗体治疗在较短的时间范围内显着增加了曲线下面积中的C肽浓度(平均差=0.114,95%CI:0.069~0.159,p=.000).此外，抗CD3单克隆抗体在所有时间范围内显著降低了患者的胰岛素摄入量(平均差=-0.123,95%CI:-0.151至-0.094,p<.001).然而,未观察到对糖化血红蛋白浓度的显著影响.
结论：本综述的结果表明，抗CD3单克隆抗体治疗可通过减少胰岛素剂量增加内源性胰岛素产生并改善患者的生活方式。未来的研究应该考虑局限性，包括样本量，异质性和随访持续时间，进一步验证这些发现的普遍性。
方法：对PubMed的全面搜索，谷歌学者，Scopus和Cochrane中央对照试验注册中心（CENTRAL）于2022年12月进行，以确定相关的随机对照试验。使用随机效应模型进行荟萃分析，计算比值比和95%置信区间(CI)以量化效果。采用Cochrane偏倚风险工具进行质量评估。
结果：总计，11项随机对照试验，涉及1397名参与者(干预组908名参与者，控制臂中的489名参与者)被纳入本综述。参与者的平均年龄是15岁,平均随访时间为2.04年。Teplizumab是最常用的研究干预措施。与安慰剂相比，抗CD3单克隆抗体治疗在较短的时间范围内显着增加了曲线下面积中的C肽浓度(平均差=0.114,95%CI:0.069~0.159,p=.000).此外，抗CD3单克隆抗体在所有时间范围内显著降低了患者的胰岛素摄入量(平均差=-0.123,95%CI:-0.151至-0.094,p<.001).然而,未观察到对糖化血红蛋白浓度的显著影响.
结论：本综述的结果表明，抗CD3单克隆抗体治疗可通过减少胰岛素剂量增加内源性胰岛素产生并改善患者的生活方式。未来的研究应该考虑局限性，包括样本量，异质性和随访持续时间，进一步验证这些发现的普遍性。
