美国耶鲁大学Kevan C. Herold团队研究了Teplizumab治疗新诊断的1型糖尿病对β-细胞功能的效果。2023年10月18日出版的《新英格兰医学杂志》发表了这项成果。

Teplizumab是一种针对T细胞CD3的人源化单克隆抗体，经美国食品药品监督管理局批准，可延缓8岁或以上临床前（2期）糖尿病患者的临床1型糖尿病（3期）发作。对于新诊断的1型糖尿病患者，静脉注射Teplizumab是否可预防疾病进展尚不清楚。

在这项临床3期随机安慰剂对照试验中，研究组评估了被分配接受Teplizumab或安慰剂治疗两个12天疗程的儿童和青少年的β细胞保存、临床终点和安全性。主要终点是通过第78周刺激C肽水平测量的β细胞功能与基线相比的变化。关键次要终点是达到血糖目标所需的胰岛素剂量、糖化血红蛋白水平、在目标葡萄糖范围内的时间以及临床上重要的低血糖事件。

在第78周，接受Teplizumab的患者（217名）刺激C肽水平显著高于接受安慰剂治疗的患者（111名）（最小二乘平均差，0.13 pmol/毫升；P<0.001），接受Teplizumab治疗的患者中，94.9%的C肽峰值水平保持在每毫升0.2 pmol或更高的临床意义峰值，而接受安慰剂治疗的患者中这一比例为79.2%。两组在关键次要终点方面没有显著差异。不良事件主要与Teplizumab或安慰剂的给药有关，包括头痛、胃肠道症状、皮疹、淋巴细胞减少和轻度细胞因子释放综合征。

研究结果表明，在新诊断为1型糖尿病的儿童和青少年中，两个为期12天的Teplizumab疗程在保存β细胞功能的主要终点方面显示出临床益处，但在次要终点方面，两组之间没有观察到显著差异。

附：英文原文

Title: Teplizumab and β-Cell Function in Newly Diagnosed Type 1 Diabetes | NEJM

Author:

Issue&Volume: 2023-10-18

Abstract:

Background

Teplizumab, a humanized monoclonal antibody to CD3 on T cells, is approved by the Food and Drug Administration to delay the onset of clinical type 1 diabetes (stage 3) in patients 8 years of age or older with preclinical (stage 2) disease. Whether treatment with intravenous teplizumab in patients with newly diagnosed type 1 diabetes can prevent disease progression is unknown.

Methods

In this phase 3, randomized, placebo-controlled trial, we assessed β-cell preservation, clinical end points, and safety in children and adolescents who were assigned to receive teplizumab or placebo for two 12-day courses. The primary end point was the change from baseline in β-cell function, as measured by stimulated C-peptide levels at week 78. The key secondary end points were the insulin doses that were required to meet glycemic goals, glycated hemoglobin levels, time in the target glucose range, and clinically important hypoglycemic events.

Results

Patients treated with teplizumab (217 patients) had significantly higher stimulated C-peptide levels than patients receiving placebo (111 patients) at week 78 (least-squares mean difference, 0.13 pmol per milliliter; 95% confidence interval [CI], 0.09 to 0.17; P<0.001), and 94.9% (95% CI, 89.5 to 97.6) of patients treated with teplizumab maintained a clinically meaningful peak C-peptide level of 0.2 pmol per milliliter or greater, as compared with 79.2% (95% CI, 67.7 to 87.4) of those receiving placebo. The groups did not differ significantly with regard to the key secondary end points. Adverse events occurred primarily in association with administration of teplizumab or placebo and included headache, gastrointestinal symptoms, rash, lymphopenia, and mild cytokine release syndrome.

Conclusions

Two 12-day courses of teplizumab in children and adolescents with newly diagnosed type 1 diabetes showed benefit with respect to the primary end point of preservation of β-cell function, but no significant differences between the groups were observed with respect to the secondary end points.

DOI: 10.1056/NEJMoa2308743

Source: https://www.nejm.org/doi/full/10.1056/NEJMoa2308743