一项前性研究,以表征患有类风湿性疾病的儿科患者的阿达利穆马布暴露
Tatjana Welzel1,2,3,4, Klervi Golhen5, Andrew Atkinson5,6,7
1Pediatric Pharmacology and Pharmacometrics, University Children's Hospital Basel, University of Basel, Basel, Switzerland. tatjana.welzel@ukbb.ch.
Pediatric rheumatology online journal
|January 3, 2024
概括
在儿科类风湿性疾病 (PRD) 中,阿达利穆马布的暴露显示出很高的可变性. 甲三酸联合治疗可能会增加阿达利穆马布水平,往往超过与类风湿性关节炎 (RA) 临床反应相关的水平.
科学领域:
- 儿科风湿病学 儿科风湿病学
- 药理动力学 药理动力学
- 免疫学 免疫学 免疫学
背景情况:
- 在儿科类风湿性疾病 (PRD) 中,阿达利穆马布的剂量是固定的,不考虑甲状腺素联合治疗或疾病活性.
- 关于PRD中阿达利穆马布的药理动力学 (PK) 的数据有限.
- 这项研究调查了在有或没有甲状腺素的PRD患者中阿达利穆马布PK的变异性.
研究的目的:
- 分析阿达利穆马布的药理动力学 (PK) 和其在儿科类风湿性疾病 (PRD) 中的变异性.
- 为了比较PRD患者的阿达利穆马布暴露,这些患者接受了阿达利穆马布加上甲状腺素治疗与阿达利穆马布单独治疗.
主要方法:
- 一项前性,两中心的研究包括28名PRD患者 (年龄为2-18岁),分为两个组:阿达利穆马布加上甲状腺素 (GA-M) 和单独的阿达利穆马布 (GA).
- 在经过≥12周治疗后,通过ELISA测量了阿达利穆马布度 (Cmax和Cmin).
- 群体之间的日志正常化Cmin的统计比较使用标准t-test进行.
主要成果:
- 28名患有青少年异常性关节炎,脑膜炎或骨质炎的患者 (每组14名) 完成了这项研究.
- 虽然GA-M具有更高的女性代表性和更长的阿达利穆马布暴露,但剂量和观察到的疾病活性在各组之间是相似的.
- 中位数Cmin值在各组之间没有统计学上的差异 (p=0.3),但GA-M显示出更高的暴露 (27%的增加) 和更频繁的Cmin≥8 mg/L (79%对64%).
- 总的来说,在PRD中观察到广泛的阿达利穆马布Cmin值 (0.5至26毫克/升).
结论:
- 在PRD中,阿达利穆马布暴露呈现出显著的异质性.
- 甲托雷克萨特联合治疗往往会增加PRD中阿达利穆马布的暴露,尽管在统计学上并不显著.
- 大多数PRD患者的阿达利穆马布暴露水平超过了与RA临床反应相关的水平,特别是在甲状腺素联合治疗时.
- 需要进一步的研究来开发个性化,基于模型的PRD治疗策略,以优化阿达利穆马布的剂量并避免暴露不足或过度.
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