METHODS: The PubMed, Embase and Cochrane databases were searched for randomized controlled trials (RCTs) comparing teplizumab to placebo for T1DM that reported any of the following outcomes: (1) C-peptide area under the curve (AUC); (2) glycated haemoglobin (HbA1c) levels; (3) insulin requirements; and (4) adverse events. Heterogeneity was examined with I2 statistics. p values <0.05 were taken to indicate statistical significance. The continuous endpoints were compared through the pooled mean difference (MD) and binary endpoints were assessed using risk ratios, both with 95% confidence intervals (CIs). Statistical analyses were performed using Review Manager Web software.
RESULTS: Eight RCTs with 1052 patients (754 receiving teplizumab) were included. Teplizumab significantly increased the AUC of C-peptide levels at 6 (MD 0.10 nmol/L, 95% CI 0.05, 0.16), 12 (MD 0.13 nmol/L, 95% CI 0.06, 0.20), 18 (MD 0.18 nmol/L, 95% CI 0.09, 0.27) and 24 months (MD 0.16 nmol/L, 95% CI 0.02, 0.31), significantly reduced HbA1c levels at 6 (MD -0.57%, 95% CI -1.07, -0.08) and 12 months (MD -0.31%, 95% CI -0.59, -0.02), and significantly reduced insulin requirements at 6 (MD -0.12 U/kg, 95% CI -0.16, -0.08), 12 (MD -0.11 U/kg, 95% CI -0.15, -0.07), 18 (MD -0.17 U/kg, 95% CI -0.26, -0.09) and 24 months (MD -0.11 U/kg, 95% CI -0.22, -0.01).
CONCLUSIONS: Teplizumab increases AUC of C-peptide levels and decreases HbA1c levels and insulin use, without raising serious adverse event risk.
方法:PubMed,搜索Embase和Cochrane数据库,以比较teplizumab与安慰剂治疗T1DM的随机对照试验(RCT),该试验报告了以下任何结果:(1)曲线下C肽面积(AUC);(2)糖化血红蛋白(HbA1c)水平;(3)胰岛素需求;(4)不良事件。用I2统计量检查异质性。P值<0.05表示统计学显著性。通过合并均值差异(MD)比较连续终点,并使用风险比评估二元终点,两者都有95%的置信区间(CI)。使用ReviewManagerWeb软件进行统计分析。
结果:共纳入8个RCTs,共1052名患者(754名接受替普利珠单抗)。Teplizumab在6时显着增加C肽水平的AUC(MD0.10nmol/L,95%CI0.05,0.16),12(MD0.13nmol/L,95%CI0.06,0.20),18(MD0.18nmol/L,95%CI0.09,0.27)和24个月(MD0.16nmol/L,95%CI0.02,0.31),6岁时HbA1c水平显着降低(MD-0.57%,95%CI-1.07,-0.08)和12个月(MD-0.31%,95%CI-0.59,-0.02),并在6时显著降低胰岛素需求(MD-0.12U/kg,95%CI-0.16,-0.08),12(MD-0.11U/kg,95%CI-0.15,-0.07),18(MD-0.17U/kg,95%CI-0.26,-0.09)和24个月(MD-0.11U/kg,95%CI-0.22,-0.01)。
结论:Teplizumab增加C肽水平的AUC,降低HbA1c水平和胰岛素使用,不增加严重不良事件风险。