Department of Clinical Pharmacy, University Medical Centre Utrecht, Utrecht University, Utrecht, The Netherlands.
Department of Pediatric Rheumatology and Immunology, Wilhelmina Children's Hospital, Utrecht University, Utrecht, The Netherlands.
Pediatr Rheumatol Online J. 2024 May 7;22(1):52. doi: 10.1186/s12969-024-00988-y.
Low-dose weekly methotrexate (MTX) is the mainstay of treatment in juvenile idiopathic arthritis. Unfortunately, a substantial part of patients has insufficient efficacy of MTX. A potential cause of this inadequate response is suboptimal drug adherence. The aim of this study was to assess MTX adherence in juvenile idiopathic arthritis patients by quantification of MTX concentrations in plasma. Secondly, the association between MTX concentrations and either self-reported adherence issues, or concomitant use of biologics was examined.
This was a retrospective, observational study using plasma samples from juvenile idiopathic arthritis patients. An ultrasensitive liquid chromatography-tandem mass spectrometry method was developed for quantification of MTX and its metabolite 7-hydroxy-MTX in plasma. The determined MTX plasma concentrations in juvenile idiopathic arthritis patients were compared with corresponding adherence limits, categorising them as either adherent or possibly non-adherent to MTX therapy.
Plasma samples of 43 patients with juvenile idiopathic arthritis were analysed. Adherence to MTX in this population was 88% shortly after initiation of MTX therapy and decreased to 77% after one year of treatment. Teenagers were more at risk for non-adherence (p = 0.002). We could not find an association between MTX adherence with either self-reported adherence issues, nor with the use of concomitant biological treatment (p = 1.00 and p = 0.27, respectively; Fisher's Exact).
Quantification of MTX in plasma is a feasible and objective method to assess adherence in patients using low-dose weekly MTX. In clinical practice, the use of this method could be a helpful tool for physicians to refute or support suspicion of non-adherence to MTX therapy.
低剂量每周甲氨蝶呤（MTX）是治疗幼年特发性关节炎的主要方法。不幸的是，相当一部分患者对 MTX 的疗效不佳。这种反应不足的一个潜在原因是药物依从性不佳。本研究旨在通过定量检测血浆中甲氨蝶呤浓度来评估幼年特发性关节炎患者的 MTX 依从性。其次，检查 MTX 浓度与自述的依从性问题或同时使用生物制剂之间的关系。
这是一项回顾性、观察性研究，使用了幼年特发性关节炎患者的血浆样本。建立了一种超灵敏的液相色谱-串联质谱法，用于定量检测血浆中甲氨蝶呤及其代谢物 7-羟基甲氨蝶呤。将确定的幼年特发性关节炎患者的 MTX 血浆浓度与相应的依从性限制进行比较，将其归类为对 MTX 治疗依从或可能不依从。
分析了 43 名幼年特发性关节炎患者的血浆样本。在开始 MTX 治疗后不久，该人群对 MTX 的依从性为 88%，治疗 1 年后降至 77%。青少年不依从的风险更高（p=0.002）。我们没有发现 MTX 依从性与自述的依从性问题之间存在关联，也没有发现与同时使用生物治疗之间存在关联（p=1.00 和 p=0.27，Fisher 精确检验）。
定量检测血浆中甲氨蝶呤是一种可行和客观的方法，可用于评估使用低剂量每周 MTX 的患者的依从性。在临床实践中，该方法的使用可能是医生反驳或支持对 MTX 治疗不依从的怀疑的有用工具。
