Mohamed Hamid J, Sorich Michael J, Kowalski Stefan M, McKinnon Ross, Proudman Susanna M, Cleland Leslie, Wiese Michael D
Pharmacy Department, Modbury Public Hospital, Modbury, South Australia, Australia.
Eur J Clin Pharmacol. 2015 Apr;71(4):411-23. doi: 10.1007/s00228-015-1819-x. Epub 2015 Feb 18.
PURPOSE: Evidence regarding the relationship between red blood cell methotrexate polyglutamate concentration and response to treatment and adverse drug reactions in patients using methotrexate for inflammatory arthropathies is complex and in some respects appears conflicting. Accordingly, we undertook a systematic analysis of available evidence to determine the clinical utility of dosing methotrexate to a target red blood cell methotrexate polyglutamate concentration. METHODS: A systematic literature review was conducted to identify all studies that had reported an association between red blood cell methotrexate polyglutamate concentration and disease activity or adverse drug reactions in users of methotrexate for the treatment of rheumatoid arthritis, juvenile idiopathic arthritis or psoriatic arthritis. RESULTS: No randomised controlled trials were identified. Thirteen studies (ten in patients with rheumatoid arthritis and three in patients with juvenile idiopathic arthritis) were identified. All studies evaluated an association between red blood cell methotrexate polyglutamate concentration and response to treatment, and eight evaluated an association with toxicity. Eight studies identified lower disease activity with at least one higher red blood cell methotrexate polyglutamate concentration, although there was at least moderate potential for bias in all of these studies. Relatively large increases in concentration appeared to be required to produce a meaningful reduction in disease activity. Only one study identified an association between red blood cell methotrexate polyglutamate concentration and methotrexate-induced side effects, although studies were likely underpowered to detect this type of association. CONCLUSIONS: The manner in which data were presented in the included studies had many limitations that hampered its conclusive assessment, but red blood cell methotrexate polyglutamate concentrations appear to be a potentially useful guide to treatment in patients with inflammatory arthropathies, but the specific polyglutamate that should be monitored and how monitoring could be integrated into treat-to-target approaches should be clarified before it can be routinely implemented.
目的：关于使用甲氨蝶呤治疗炎性关节病的患者中，红细胞甲氨蝶呤聚谷氨酸盐浓度与治疗反应及药物不良反应之间关系的证据较为复杂，在某些方面似乎相互矛盾。因此，我们对现有证据进行了系统分析，以确定根据目标红细胞甲氨蝶呤聚谷氨酸盐浓度调整甲氨蝶呤剂量的临床实用性。 方法：进行了一项系统的文献综述，以识别所有报告了使用甲氨蝶呤治疗类风湿关节炎、幼年特发性关节炎或银屑病关节炎的患者中，红细胞甲氨蝶呤聚谷氨酸盐浓度与疾病活动或药物不良反应之间关联的研究。 结果：未识别到随机对照试验。共识别出13项研究（10项针对类风湿关节炎患者，3项针对幼年特发性关节炎患者）。所有研究均评估了红细胞甲氨蝶呤聚谷氨酸盐浓度与治疗反应之间的关联，8项研究评估了与毒性的关联。8项研究发现，至少有一个较高的红细胞甲氨蝶呤聚谷氨酸盐浓度与较低的疾病活动相关，尽管所有这些研究都至少存在中度偏倚的可能性。似乎需要相对大幅提高浓度才能使疾病活动有意义地降低。只有一项研究发现红细胞甲氨蝶呤聚谷氨酸盐浓度与甲氨蝶呤引起的副作用之间存在关联，尽管这些研究可能因效能不足而无法检测到这种关联。 结论：纳入研究中呈现数据的方式存在许多局限性，妨碍了对其进行确定性评估，但红细胞甲氨蝶呤聚谷氨酸盐浓度似乎是炎性关节病患者治疗的潜在有用指导，但在常规实施之前，应明确应监测的具体聚谷氨酸盐以及如何将监测纳入达标治疗方法中。
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