蒂尔泽帕提德免疫性对药理动力学,有效性和安全性:分析第三阶段研究数据
Garrett R Mullins1, Michael E Hodsdon1, Ying Grace Li1
1Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN 46285, USA.
The Journal of clinical endocrinology and metabolism
|September 13, 2023
概括
在超过一半的患者中检测到与治疗相关的抗药抗体 (ADA) 对抗提尔泽帕提德 (TZP),但没有影响药物的药理动力学或疗效. 大多数ADA阳性患者的过敏反应或注射部位反应都是轻微的.
科学领域:
- 药理学 药理学是指药理学的学科.
- 免疫学 免疫学 免疫学
- 内分泌学 在内分泌学.
背景情况:
- 抗药抗体 (ADA) 可以影响药物的药理动力学,安全性和疗效.
- 了解ADA的发展对于治疗性蛋白质的评估至关重要.
研究的目的:
- 为了评估治疗新出现的 (TE) ADA在7个第3阶段试验中,对TZP治疗的参与者进行治疗.
- 评估TE ADA对TZP药理动力学,疗效和安全性的影响.
主要方法:
- 在7个第三阶段试验中,对5025名2型糖尿病患者进行了ADA评估,这些患者接受了TZP (5,10或15毫克) 治疗.
- ADA的特点是对TZP,GNIP和nGLP-1的交叉反应和中和能力.
- 分析了与TE ADA状态相关的药理动力学,疗效和安全数据.
主要成果:
- 在接受TZP治疗的患者中,TE ADA发生在51.1%的患者中,剂量组之间的比例相似.
- 对TZP活性的中和抗体 (NAb) 在<2.1%的患者中观察到;对 nGIP/nGLP-1的交叉反应NAb为<1.0%.
- TE ADA状态,标位或NAb状态没有影响TZP的药理动力学或疗效,但TE ADA+患者有更多的过敏和注射部位反应,大多是轻微的.
结论:
- 根据TE ADA测量的免疫性,没有影响TZP的药理动力学或疗效.
- 在TE ADA+患者中,过敏和注射部位反应主要为轻度至中度.
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