在接受长期甲氨蝶呤治疗的类风湿关节炎患者中，甲氨蝶呤多聚谷氨酸盐浓度与疾病控制无关。

Methotrexate polyglutamate concentrations are not associated with disease control in rheumatoid arthritis patients receiving long-term methotrexate therapy.

作者信息

Stamp Lisa K, O'Donnell John L, Chapman Peter T, Zhang Mei, James Jill, Frampton Christopher, Barclay Murray L

机构信息

University of Otago, Christchurch, New Zealand.

出版信息

Arthritis Rheum. 2010 Feb;62(2):359-68. doi: 10.1002/art.27201.

DOI:10.1002/art.27201

PMID:20112376

Abstract

OBJECTIVE

There are limited data suggesting that methotrexate polyglutamate (MTXGlu) concentrations can guide MTX dosing in patients with rheumatoid arthritis (RA). The aim of this study was to define a therapeutic range of red blood cell (RBC) MTXGlu(n) concentrations (where n refers to the number of glutamate groups), including threshold values for efficacy and adverse effects in patients receiving long-term oral MTX treatment.

METHODS

A cross-sectional study of 192 patients receiving oral MTX was undertaken. Disease activity was assessed by the swollen and tender joint counts, the C-reactive protein level, and the Disease Activity Score in 28 joints (DAS28). High disease activity was defined as a DAS28 of >3.2. A standardized questionnaire regarding common MTX adverse effects was completed.

RESULTS

The MTX dosage was significantly higher in patients in whom the swollen joint count and DAS28 were higher. The MTXGlu(4), MTXGlu(5), MTXGlu(3-5), and MTXGlu(1-5) concentrations were significantly higher in patients with high disease activity. After correction for age, the estimated glomerular filtration rate, and the MTX dosage, the association remained significant for MTXGlu(5). RBC folate concentrations were significantly higher in the group with high disease activity. There was no association between any MTXGlu(n) concentration and adverse effects.

CONCLUSION

In contrast to other studies, the results of the present study did not show a relationship between the MTXGlu(n) concentration and reduced disease activity in patients with RA who were receiving long-term MTX therapy. However, disease activity was influenced by the RBC folate level, which may be a more important factor than MTXGlu(n) concentrations for disease control. In accordance with the findings of previous studies, we were unable to show a relationship between MTXGlu(n) concentrations and adverse effects. Prospective studies will be important to determine whether there is a role for measuring MTXGlu(n) concentrations in patients receiving long-term treatment with MTX.

摘要

目的

仅有有限的数据表明甲氨蝶呤多聚谷氨酸盐（MTXGlu）浓度可指导类风湿关节炎（RA）患者的甲氨蝶呤剂量调整。本研究的目的是确定红细胞（RBC）MTXGlu(n)浓度的治疗范围（其中n指谷氨酸基团的数量），包括接受长期口服甲氨蝶呤治疗患者的疗效阈值和不良反应阈值。

方法

对192例接受口服甲氨蝶呤的患者进行了横断面研究。通过肿胀和压痛关节计数、C反应蛋白水平以及28个关节的疾病活动评分（DAS28）评估疾病活动度。高疾病活动度定义为DAS28>3.2。完成了一份关于常见甲氨蝶呤不良反应的标准化问卷。

结果

肿胀关节计数和DAS28较高的患者甲氨蝶呤剂量显著更高。高疾病活动度患者的MTXGlu(4)、MTXGlu(5)、MTXGlu(3 - 5)和MTXGlu(1 - 5)浓度显著更高。在校正年龄、估计肾小球滤过率和甲氨蝶呤剂量后，MTXGlu(5)的相关性仍然显著。高疾病活动度组的红细胞叶酸浓度显著更高。任何MTXGlu(n)浓度与不良反应之间均无关联。

结论

与其他研究不同，本研究结果未显示接受长期甲氨蝶呤治疗的RA患者中MTXGlu(n)浓度与疾病活动度降低之间存在关联。然而，疾病活动度受红细胞叶酸水平影响，对于疾病控制而言其可能是比MTXGlu(n)浓度更重要的因素。根据先前研究的结果，我们未能显示MTXGlu(n)浓度与不良反应之间存在关联。前瞻性研究对于确定在接受甲氨蝶呤长期治疗的患者中测量MTXGlu(n)浓度是否有作用至关重要。