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戈利木单抗与年轻新发1型糖尿病患者的β细胞功能
Golimumab and Beta-Cell Function in Youth with New-Onset Type 1 Diabetes


Teresa Quattrin ... 糖尿病 • 2020.11.19
相关阅读
• 1型糖尿病患儿应用闭环系统控制血糖的随机试验 • 1型糖尿病患者胰岛素治疗中加用sotagliflozin的效果

摘要


背景

1型糖尿病是以胰腺β细胞进行性减少为特征的自身免疫病。戈利木单抗是肿瘤坏死因子α特异性人单克隆抗体,已被批准用于治疗成人和儿童的数种自身免疫病。目前尚不清楚戈利木单抗是否有助于保留新诊断出显性(3期)1型糖尿病的年轻患者的β细胞功能。

 

方法

在这项2期、多中心、安慰剂对照、双盲、平行组对照试验中,我们以2∶1的比例将新诊断出显性1型糖尿病的儿童和年轻成人患者(年龄范围,6~21岁)随机分组,两组分别接受为期52周的戈利木单抗或安慰剂皮下给药治疗。主要终点是第52周时的内源性胰岛素生成量,评估指标是对4小时混合膳食耐受试验做出应答后,C肽水平的浓度-时间曲线下面积(4小时C肽AUC)。次要终点和其他终点包括胰岛素用量、糖化血红蛋白水平、低血糖事件数量、随时间推移的空腹胰岛素原与C肽比值以及应答曲线。

 

结果

共计84例参与者接受了随机分组:56例被分配至戈利木单抗组,28例被分配至安慰剂组。第52周时,戈利木单抗组和安慰剂组的平均(±SD)4小时C肽AUC有显著差异(0.64±0.42 pmol/mL vs. 0.43±0.39 pmol/mL,P<0.001)。达标治疗方法(treat-to-target approach)在两组中均实现了良好的血糖控制,且两组的糖化血红蛋白水平无显著差异。戈利木单抗组的胰岛素用量比安慰剂组少。戈利木单抗组43%的参与者和安慰剂组7%的参与者达到了部分缓解(定义为根据胰岛素剂量校正的糖化血红蛋白水平评分[计算方法是糖化血红蛋白水平+4×胰岛素剂量]≤9分)(差异,36个百分点;95% CI,22~55)。两组的低血糖事件平均数量无差异。根据研究者的判断,戈利木单抗组13例参与者(23%)和安慰剂组2例参与者(7%)发生了被记录为不良事件的低血糖事件。我们在接受药物治疗的30例参与者体内检出戈利木单抗抗体;29例参与者的抗体滴度低于1∶1,000,其中12例的中和抗体结果为阳性。

 

结论

在新诊断出显性1型糖尿病的儿童和年轻成人患者中,与安慰剂组相比,戈利木单抗组的内源性胰岛素生成量较多,外源性胰岛素用量较少(由Janssen Research and Development资助;T1GER在ClinicalTrials.gov注册号为NCT02846545)。





作者信息

Teresa Quattrin, M.D., Michael J. Haller, M.D., Andrea K. Steck, M.D., Eric I. Felner, M.D., Yinglei Li, Ph.D., Yichuan Xia, Ph.D., Jocelyn H. Leu, Pharm.D., Ph.D., Ramineh Zoka, Pharm.D., Joseph A. Hedrick, Ph.D., Mark R. Rigby, M.D., Ph.D., and Frank Vercruysse, M.D. for the T1GER Study Investigators*
From the Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, and Diabetes Center, John R. Oishei Children’s Hospital, Buffalo, NY (T.Q.); the Department of Pediatrics, University of Florida, Gainesville (M.J.H.); the Barbara Davis Center for Diabetes, University of Colorado Anschutz Medical Campus, Aurora (A.K.S.); the Division of Pediatric Endocrinology, Emory University School of Medicine, Atlanta (E.I.F.); Janssen Research and Development, Spring House (Y.L., Y.X., J.H.L.) and Horsham (R.Z., J.A.H., M.R.R.) — both in Pennsylvania; and Janssen Research and Development, Beerse, Belgium (F.V.). Address reprint requests to Dr. Quattrin at the Department of Pediatrics, Jacobs School of Medicine and Biomedical Sciences, 1001 Main St., 5th Fl., Buffalo, NY 14203, or at tquattrin@upa.chob.edu. *A complete list of the investigators in the T1GER Study is provided in the Supplementary Appendix, available at NEJM.org.

 

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