PDF(Pubmed)
Abstract：
BACKGROUND: 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.
METHODS: 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.
RESULTS: 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).
CONCLUSIONS: 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.
METHODS: 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.
RESULTS: 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).
CONCLUSIONS: 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.
摘要：
背景：每周小剂量甲氨蝶呤（MTX）是治疗幼年特发性关节炎的主要药物。不幸的是,相当一部分患者的MTX疗效不足。这种不充分反应的潜在原因是药物依从性欠佳。这项研究的目的是通过定量血浆中的MTX浓度来评估青少年特发性关节炎患者的MTX依从性。其次,MTX浓度与自我报告的依从性问题之间的关联，或同时使用生物制剂进行了检查。
方法：这是一个回顾性研究，使用幼年特发性关节炎患者血浆样本的观察性研究。建立了一种超灵敏的液相色谱-串联质谱法，用于定量血浆中MTX及其代谢物7-羟基-MTX。将测定的青少年特发性关节炎患者的MTX血浆浓度与相应的依从性限值进行比较，将它们归类为粘附或可能不粘附MTX治疗。
结果：分析了43例幼年特发性关节炎患者的血浆样本。MTX治疗开始后不久，该人群对MTX的依从性为88％，治疗一年后下降至77％。青少年更容易出现不依从(p=0.002)。我们找不到MTX依从性与任何自我报告的依从性问题之间的关联，也不使用伴随的生物治疗（分别为p=1.00和p=0.27；Fisher精确）。
结论：血浆中MTX的定量是评估每周低剂量MTX患者依从性的可行且客观的方法。在临床实践中,这种方法的使用可能是医师反驳或支持不坚持MTX治疗的有用工具.
方法：这是一个回顾性研究，使用幼年特发性关节炎患者血浆样本的观察性研究。建立了一种超灵敏的液相色谱-串联质谱法，用于定量血浆中MTX及其代谢物7-羟基-MTX。将测定的青少年特发性关节炎患者的MTX血浆浓度与相应的依从性限值进行比较，将它们归类为粘附或可能不粘附MTX治疗。
结果：分析了43例幼年特发性关节炎患者的血浆样本。MTX治疗开始后不久，该人群对MTX的依从性为88％，治疗一年后下降至77％。青少年更容易出现不依从(p=0.002)。我们找不到MTX依从性与任何自我报告的依从性问题之间的关联，也不使用伴随的生物治疗（分别为p=1.00和p=0.27；Fisher精确）。
结论：血浆中MTX的定量是评估每周低剂量MTX患者依从性的可行且客观的方法。在临床实践中,这种方法的使用可能是医师反驳或支持不坚持MTX治疗的有用工具.
