Department of Paediatric Immunology and Rheumatology, Wilhelmina Children's Hospital, University Medical Centre Utrecht, Utrecht, The Netherlands.
Faculty of Medicine, Utrecht University, Utrecht, The Netherlands.
Rheumatology (Oxford). 2021 Dec 24;61(1):377-382. doi: 10.1093/rheumatology/keab354.
The objective of this study was to assess the relationship between adalimumab trough concentrations and treatment response in paediatric patients with JIA.
This was a monocentric cohort study of JIA patients treated with adalimumab. Clinical data and samples were collected during routine follow-up. Adalimumab trough concentrations were quantified by a novel liquid chromatography-tandem mass spectrometry assay. Anti-adalimumab antibodies were measured in samples with trough concentrations of ≤5mg/l. Disease activity was evaluated using the clinical Juvenile Arthritis DAS with 71-joint count (cJADAS71). Response to adalimumab was defined according to recent international treat-to-target guidelines.
A total of 35 adalimumab trough samples were available from 34 paediatric patients with JIA. Although there was no significant difference in adalimumab dose, trough concentrations were significantly lower in patients with secondary failure [median 1.0 mg/l; interquartile range (IQR) 1.0-5.3] compared with patients with primary failure (median 13.97 mg/l; IQR 11.81-16.67) or an adequate response (median 14.94 mg/l; IQR 10.31-16.19) to adalimumab.
Adalimumab trough concentrations were significantly lower in JIA patients with secondary failure compared with patients with primary failure or an adequate response to adalimumab. Our results suggest that trough concentration measurements could identify JIA patients who require increased adalimumab doses to achieve or maintain therapeutic drug concentrations.
本研究旨在评估幼年特发性关节炎(JIA)患儿阿达木单抗谷浓度与治疗反应之间的关系。
这是一项采用阿达木单抗治疗的 JIA 患者的单中心队列研究。临床数据和样本在常规随访期间收集。阿达木单抗谷浓度采用新型液相色谱-串联质谱法进行定量。在谷浓度≤5mg/l 的样本中检测抗阿达木单抗抗体。采用包含 71 个关节的临床幼年特发性关节炎疾病活动度评分(cJADAS71)评估疾病活动度。根据最近的国际达标治疗指南定义阿达木单抗的治疗反应。
共 34 例 JIA 患儿的 35 个阿达木单抗谷样本可用。尽管阿达木单抗剂量无显著差异,但继发失效患者的阿达木单抗谷浓度明显较低[中位数 1.0mg/l;四分位距(IQR)1.0-5.3],与原发失效(中位数 13.97mg/l;IQR 11.81-16.67)或阿达木单抗治疗有充分反应的患者(中位数 14.94mg/l;IQR 10.31-16.19)相比。
与阿达木单抗治疗有原发失效或充分反应的 JIA 患者相比,继发失效患者的阿达木单抗谷浓度明显较低。我们的结果表明,谷浓度测量可能有助于确定需要增加阿达木单抗剂量以达到或维持治疗药物浓度的 JIA 患者。