Efficacy of anti-CD3 monoclonal antibodies in delaying the progression of recent-onset type 1 diabetes mellitus: A systematic review, meta-analyses and meta-regression

IF 5.4 2区医学 Q1 ENDOCRINOLOGY & METABOLISM

Diabetes, Obesity & Metabolism Pub Date : 2023-08-14 DOI:10.1111/dom.15237

Muhammad Talal Ashraf MBBS, Syed Hassan Ahmed Rizvi MBBS, Muhammad Arham Bin Kashif MBBS, Muhammad Khuzzaim Shakeel Khan MBBS, Syed Hassan Ahmed MBBS, Muhammad Sohaib Asghar MBBS, MD

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引用次数: 1

Abstract

Aim

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.

Methods

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.

Results

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.

Conclusion

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.

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抗CD3单克隆抗体延缓新发1型糖尿病进展的疗效：系统综述、荟萃分析和荟萃回归

目的1型糖尿病是一种公认的慢性自身免疫性疾病，其特征是β细胞的致病性破坏，导致内源性胰岛素产生的损失。胰岛素给药仍然是症状治疗的主要治疗方法。最近的研究表明，疾病修饰剂，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，替普利珠单抗获得了美国食品药品监督管理局（FDA）的批准，成为第一种治疗1型糖尿病的疾病调节剂。本综述旨在评估抗CD3单克隆抗体在预防和治疗1型糖尿病中的疗效的临床证据。方法截至2022年12月，对PubMed、Google Scholar、Scopus和Cochrane Central Register of Controlled Trials（Central）进行全面检索，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，并计算95%置信区间（CI）的比值比以量化效应。采用Cochrane偏倚风险工具进行质量评估。结果本综述共纳入11项随机对照试验，涉及1397名参与者（干预组908名参与者，对照组489名参与者）。参与者的平均年龄为15岁年，平均随访时间为2.04 年。特普利珠单抗是最常被研究的干预措施。与安慰剂相比，抗CD3单克隆抗体治疗在更短的时间内显著增加了曲线下区域的C肽浓度（平均差异 = 0.114，95%置信区间：0.069至0.159，p = .000）。此外，抗CD3单克隆抗体在所有时间段内显著降低了患者的胰岛素摄入量（平均差异 = −0.123，95%置信区间：−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的产生，改善患者的生活方式。未来的研究应考虑局限性，包括样本量、异质性和随访时间，以进一步验证这些发现的可推广性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Diabetes, Obesity & Metabolism 医学-内分泌学与代谢

CiteScore

10.90

自引率

6.90%

发文量

319

审稿时长

3-8 weeks

期刊介绍： Diabetes, Obesity and Metabolism is primarily a journal of clinical and experimental pharmacology and therapeutics covering the interrelated areas of diabetes, obesity and metabolism. The journal prioritises high-quality original research that reports on the effects of new or existing therapies, including dietary, exercise and lifestyle (non-pharmacological) interventions, in any aspect of metabolic and endocrine disease, either in humans or animal and cellular systems. ‘Metabolism’ may relate to lipids, bone and drug metabolism, or broader aspects of endocrine dysfunction. Preclinical pharmacology, pharmacokinetic studies, meta-analyses and those addressing drug safety and tolerability are also highly suitable for publication in this journal. Original research may be published as a main paper or as a research letter.