Insulin needs after CD3-antibody therapy in new-onset type 1 diabetes
Insulin needs after CD3-antibody therapy in new-onset type 1 diabetes
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DOI：
10.1056/nejmoa043980
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发表时间：
2005-06-23
影响因子：
158.5
通讯作者：
Chatenoud, L
中科院分区：
文献类型：
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作者：
Keymeulen, B;Vandemeulebroucke, E;Chatenoud, L
背景1型糖尿病是一种T细胞介导的自身免疫性疾病，导致胰岛素分泌β细胞的大量丢失。临床发作后β细胞功能的进一步下降可通过CD 3单克隆抗体治疗来预防，如I期研究结果所示。为了提供这种治疗原则在代谢水平的证据，我们开始了2期安慰剂对照试验与人源化抗体，一个无糖基化的人IgG 1抗体针对CD 3（ChAglyCD 3）。MethodsIn一项多中心研究，80例新发1型糖尿病患者随机分配接受安慰剂或ChAglyCD 3连续6天。患者进行了为期18个月的随访，在此期间，他们的日常胰岛素需求和残余β细胞功能进行了评估，根据葡萄糖钳夹诱导的C-肽释放之前和之后的管理glucagon.ResultsAt 6，12，和18个月，残余β细胞功能更好地保持ChAglyCD 3比安慰剂。安慰剂组胰岛素剂量增加，但ChAglyCD 3组未增加。ChAglyCD 3的这种作用在80名患者中初始残留β细胞功能等于或高于第50百分位数的患者中最为明显。在这个亚组中，18个月时ChAglyCD 3组的平均胰岛素剂量为0.22 IU/kg体重/天，而安慰剂组为0.61 IU/kg体重/天（P
BackgroundType 1 diabetes mellitus is a T-cell-mediated autoimmune disease that leads to a major loss of insulin-secreting beta cells. The further decline of beta-cell function after clinical onset might be prevented by treatment with CD3 monoclonal antibodies, as suggested by the results of a phase 1 study. To provide proof of this therapeutic principle at the metabolic level, we initiated a phase 2 placebo-controlled trial with a humanized antibody, an aglycosylated human IgG1 antibody directed against CD3 (ChAglyCD3).MethodsIn a multicenter study, 80 patients with new-onset type 1 diabetes were randomly assigned to receive placebo or ChAglyCD3 for six consecutive days. Patients were followed for 18 months, during which their daily insulin needs and residual beta-cell function were assessed according to glucose-clamp-induced C-peptide release before and after the administration of glucagon.ResultsAt 6, 12, and 18 months, residual beta-cell function was better maintained with ChAglyCD3 than with placebo. The insulin dose increased in the placebo group but not in the ChAglyCD3 group. This effect of ChAglyCD3 was most pronounced among patients with initial residual beta-cell function at or above the 50th percentile of the 80 patients. In this subgroup, the mean insulin dose at 18 months was 0.22 IU per kilogram of body weight per day with ChAglyCD3, as compared with 0.61 IU per kilogram with placebo (P