Abstract：
OBJECTIVE: Teplizumab has emerged as a potential disease-modifying drug in type 1 diabetes (T1D). This meta-analysis sought to summarize the therapeutic effect of teplizumab in newly diagnosed patients with T1D.
METHODS: Randomized controlled trials involving patients with T1D receiving teplizumab in the intervention arm and placebo (or no active intervention) in the control arm were searched throughout the electronic databases. The primary outcome was the change in area under the curve of C-peptide levels from baseline.
RESULTS: Seven reports from 6 studies involving 834 subjects met the inclusion criteria. Compared to teplizumab, greater reductions in area under the curve of C-peptide from the baseline values were observed in the control group after 6 months (mean difference [MD] 0.07 nmol/L [0.01, 0.13], P = .02), after 12 months (MD 0.07 nmol/L [0.04, 0.11], P = .0001), after 18 months (MD 0.10 nmol/L [0.06, 0.14], P < .00001), and after 24 months (MD 0.07 nmol/L [0.01, 0.14], P = .03) of interventions. Moreover, fewer patients treated with teplizumab had a decreased C-peptide response after 6 months (odds ratio [OR] 0.21), after 12 months (OR 0.17), after 18 months (OR 0.30), and after 24 months (OR 0.12) of treatment. The preservation of endogenous insulin production was supported by reduced use of exogenous insulin with maintenance of comparable glycemic control for up to 18 months post-treatment. Teplizumab imparted higher risks of grade 3 or higher adverse events, adverse events leading to study medication discontinuation, nausea, rash, and lymphopenia.
CONCLUSIONS: The results of the meta-analysis support teplizumab as a promising disease-modifying therapy for newly diagnosed T1D.
METHODS: Randomized controlled trials involving patients with T1D receiving teplizumab in the intervention arm and placebo (or no active intervention) in the control arm were searched throughout the electronic databases. The primary outcome was the change in area under the curve of C-peptide levels from baseline.
RESULTS: Seven reports from 6 studies involving 834 subjects met the inclusion criteria. Compared to teplizumab, greater reductions in area under the curve of C-peptide from the baseline values were observed in the control group after 6 months (mean difference [MD] 0.07 nmol/L [0.01, 0.13], P = .02), after 12 months (MD 0.07 nmol/L [0.04, 0.11], P = .0001), after 18 months (MD 0.10 nmol/L [0.06, 0.14], P < .00001), and after 24 months (MD 0.07 nmol/L [0.01, 0.14], P = .03) of interventions. Moreover, fewer patients treated with teplizumab had a decreased C-peptide response after 6 months (odds ratio [OR] 0.21), after 12 months (OR 0.17), after 18 months (OR 0.30), and after 24 months (OR 0.12) of treatment. The preservation of endogenous insulin production was supported by reduced use of exogenous insulin with maintenance of comparable glycemic control for up to 18 months post-treatment. Teplizumab imparted higher risks of grade 3 or higher adverse events, adverse events leading to study medication discontinuation, nausea, rash, and lymphopenia.
CONCLUSIONS: The results of the meta-analysis support teplizumab as a promising disease-modifying therapy for newly diagnosed T1D.
摘要：
背景：Teplizumab已成为1型糖尿病（T1D）的潜在疾病改善药物。这项荟萃分析旨在总结替普单抗在新诊断的T1D患者中的治疗效果。
方法：在整个电子数据库中搜索涉及T1D患者在干预组接受teplizumab和对照组接受安慰剂（或无主动干预）的随机对照试验（RCT）。主要结果是C肽水平从基线的曲线下面积(AUC)的变化。
结果：来自6项研究的7份报告，涉及834名受试者，符合纳入标准。与替普利单抗相比,6个月后，在对照组中观察到C肽的AUC从基线值有更大的降低（MD0.07nmol/L[0.01,0.13]，P=0.02),12个月后（MD0.07nmol/L[0.04，0.11]，P=0.0001),18个月后（MD0.10nmol/L[0.06，0.14]，P<0.00001),24个月后(MD0.07nmol/L[0.01，0.14]，干预措施的P=0.03）。此外，替普利珠单抗治疗6个月后C肽反应降低的患者较少(OR0.21),12个月后（OR0.17），治疗18个月后（OR0.30）和24个月后（OR0.12）。内源性胰岛素生产的保留得到了减少外源性胰岛素使用的支持，并在治疗后18个月内维持了可比的血糖控制。Teplizumab赋予更高的3级或更高的不良事件（AE）的风险，导致研究药物停药的AE，恶心,皮疹,和淋巴细胞减少症。
结论：荟萃分析的结果支持替普利珠单抗作为新诊断的T1D的一种有希望的疾病改善疗法。
方法：在整个电子数据库中搜索涉及T1D患者在干预组接受teplizumab和对照组接受安慰剂（或无主动干预）的随机对照试验（RCT）。主要结果是C肽水平从基线的曲线下面积(AUC)的变化。
结果：来自6项研究的7份报告，涉及834名受试者，符合纳入标准。与替普利单抗相比,6个月后，在对照组中观察到C肽的AUC从基线值有更大的降低（MD0.07nmol/L[0.01,0.13]，P=0.02),12个月后（MD0.07nmol/L[0.04，0.11]，P=0.0001),18个月后（MD0.10nmol/L[0.06，0.14]，P<0.00001),24个月后(MD0.07nmol/L[0.01，0.14]，干预措施的P=0.03）。此外，替普利珠单抗治疗6个月后C肽反应降低的患者较少(OR0.21),12个月后（OR0.17），治疗18个月后（OR0.30）和24个月后（OR0.12）。内源性胰岛素生产的保留得到了减少外源性胰岛素使用的支持，并在治疗后18个月内维持了可比的血糖控制。Teplizumab赋予更高的3级或更高的不良事件（AE）的风险，导致研究药物停药的AE，恶心,皮疹,和淋巴细胞减少症。
结论：荟萃分析的结果支持替普利珠单抗作为新诊断的T1D的一种有希望的疾病改善疗法。
