Teplizumab: A Disease-Modifying Therapy for Type 1 Diabetes That Preserves β-Cell Function.

IF 14.8 1区 医学 Q1 ENDOCRINOLOGY & METABOLISM
Diabetes Care Pub Date : 2023-10-01 DOI:10.2337/dc23-0675
Kevan C Herold, Stephen E Gitelman, Peter A Gottlieb, Laura A Knecht, Ralph Raymond, Eleanor L Ramos
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Abstract

Objective: In November 2022, teplizumab-mzwv became the first drug approved to delay the onset of stage 3 type 1 diabetes in adults and children age ≥8 years with stage 2 type 1 diabetes on the basis of data from the pivotal study TN-10.

Research design and methods: To provide confirmatory evidence of the effects of teplizumab on preserving endogenous insulin production, an integrated analysis of C-peptide data from 609 patients (n = 375 patients receiving teplizumab and n = 234 control patients) from five clinical trials in stage 3 type 1 diabetes was conducted.

Results: The primary outcome of the integrated analysis, change from baseline in stimulated C-peptide, was significantly improved at years 1 (average increase 0.08 nmol/L; P < 0.0001) and 2 (average increase 0.12 nmol/L; P < 0.0001) after one or two courses of teplizumab. An analysis of exogenous insulin use was also conducted, showing overall reductions of 0.08 (P = 0.0001) and 0.10 units/kg/day (P < 0.0001) at years 1 and 2, respectively. An integrated safety analysis of five clinical trials that enrolled 1,018 patients with stage 2 or 3 type 1 diabetes (∼1,500 patient-years of follow-up for teplizumab-treated patients) was conducted.

Conclusions: These data confirm consistency in the preservation of β-cell function, as measured by C-peptide, across multiple clinical trials. This analysis showed that the most common adverse events included lymphopenia, rash, and headache, a majority of which occurred during and after the first few weeks of teplizumab administration and generally resolved without intervention, consistent with a safety profile characterized by self-limited adverse events after one or two courses of teplizumab treatment.

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特普利珠单抗:一种保留β细胞功能的1型糖尿病疾病改良疗法。
目的:2022年11月,在关键研究TN-10的数据基础上,替普利珠单抗mzvv成为首个被批准用于延迟成人和≥8岁的2型糖尿病儿童3期1型糖尿病发作的药物。研究设计和方法:为替普利珠mab在保持内源性胰岛素产生方面的作用提供验证性证据,对来自3期1型糖尿病5项临床试验的609名患者(n=375名接受替普利珠单抗治疗的患者和n=234名对照患者)的C肽数据进行了综合分析。结果:综合分析的主要结果,即刺激的C肽与基线相比的变化,在接受一个或两个疗程的替普利珠单抗治疗后的第1年(平均增加0.08 nmol/L;P<0.0001)和第2年(平均提高0.12 nmol/L,P<0.0001)显著改善。还对外源性胰岛素的使用进行了分析,结果显示,在第1年和第2年,总体胰岛素使用量分别减少了0.08(P=0.0001)和0.10单位/kg/天(P<0.0001)。对5项临床试验进行了综合安全性分析,纳入了1018名2或3期1型糖尿病患者(替普利珠单抗治疗患者的随访时间约为1500患者年)。结论:这些数据证实了在多个临床试验中,通过C肽测量的β细胞功能的保存是一致的。该分析表明,最常见的不良事件包括淋巴细胞减少、皮疹和头痛,其中大多数发生在替普利珠单抗给药的前几周期间和之后,通常在不干预的情况下解决,这与一个或两个疗程的替普利珠mab治疗后自限性不良事件的安全性特征一致。
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来源期刊
Diabetes Care
Diabetes Care 医学-内分泌学与代谢
CiteScore
27.80
自引率
4.90%
发文量
449
审稿时长
1 months
期刊介绍: The journal's overarching mission can be captured by the simple word "Care," reflecting its commitment to enhancing patient well-being. Diabetes Care aims to support better patient care by addressing the comprehensive needs of healthcare professionals dedicated to managing diabetes. Diabetes Care serves as a valuable resource for healthcare practitioners, aiming to advance knowledge, foster research, and improve diabetes management. The journal publishes original research across various categories, including Clinical Care, Education, Nutrition, Psychosocial Research, Epidemiology, Health Services Research, Emerging Treatments and Technologies, Pathophysiology, Complications, and Cardiovascular and Metabolic Risk. Additionally, Diabetes Care features ADA statements, consensus reports, review articles, letters to the editor, and health/medical news, appealing to a diverse audience of physicians, researchers, psychologists, educators, and other healthcare professionals.
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