甲氨蝶呤治疗类风湿关节炎的量效关系研究

贺龙全; 石颖; 邹庆华; 万萍; 钟兵; 方勇飞

doi:10.16016/j.1000-5404.202003380

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甲氨蝶呤治疗类风湿关节炎的量效关系研究

临床医学 | 更新时间：2026-01-09

- 甲氨蝶呤治疗类风湿关节炎的量效关系研究
- Relationship between methotrexate dose and clinical efficacy for treatment of rheumatoid arthritis
- 第三军医大学学报 2020年42卷第18期页码：1853-1858
- 作者机构：
  
  400038 重庆，陆军军医大学(第三军医大学)第一附属医院中医与风湿免疫科
- 作者简介：
  
  [ 方勇飞, E-mail: fyfalan@163.com FANG Yongfei, E-mail: fyfalan@163.com
- 基金信息：
  
  重庆市卫生技术推广基金(2017jstg36)
- DOI：10.16016/j.1000-5404.202003380
  中图分类号： R593.22; R969.4; R979.12
- 收稿：2020-03-30，
  
  修回：2020-05-22，
  
  纸质出版：2020-09-30
- 稿件说明：
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贺龙全, 石颖, 邹庆华, 等. 甲氨蝶呤治疗类风湿关节炎的量效关系研究[J]. 第三军医大学学报, 2020,42(18):1853-1858.

Longquan HE, Ying SHI, Qinghua ZOU, et al. Relationship between methotrexate dose and clinical efficacy for treatment of rheumatoid arthritis[J]. Journal of Third Military Medical University, 2020, 42(18): 1853-1858.
贺龙全, 石颖, 邹庆华, 等. 甲氨蝶呤治疗类风湿关节炎的量效关系研究[J]. 第三军医大学学报, 2020,42(18):1853-1858. DOI： 10.16016/j.1000-5404.202003380.

Longquan HE, Ying SHI, Qinghua ZOU, et al. Relationship between methotrexate dose and clinical efficacy for treatment of rheumatoid arthritis[J]. Journal of Third Military Medical University, 2020, 42(18): 1853-1858. DOI： 10.16016/j.1000-5404.202003380.

摘要

目的

研究甲氨蝶呤(methotrexate

MTX)剂量与多聚谷氨酸化MTX(MTX-PGs)浓度、疗效的关系，探索MTX治疗类风湿关节炎(rheumatoid arthritis

RA)的最佳初始有效剂量。

方法

回顾性分析本院2014年11月至2019年6月服用MTX治疗的RA患者165例，依据每周MTX口服剂量分为10 mg组、12.5 mg组、15 mg组，计算治疗前和治疗8周后的28个关节疾病活动评分(DAS28)，并根据欧洲抗风湿联盟(EULAR)疗效判定标准分为总有效(显效、有效)、无效；采用高效液相色谱质谱串联法检测MTX-PGs浓度，分析MTX剂量与疗效、治疗后DAS28、MTX-PGs浓度间的关系。

结果

① MTX剂量与疗效关系:10 mg、12.5 mg、15 mg各组的总有效率分别为37.31%、57.58%、56.25%，10 mg组总有效率低于12.5 mg组总有效率，差异具有统计学意义(

0.05)；② MTX剂量与治疗后DAS28关系:10 mg、12.5 mg、15 mg各组治疗后DAS28分别为:3.92(2.13

5.15)、2.80(1.81

4.22)、2.96(2.26

3.67)，10 mg组治疗后DAS28显著高于12.5 mg

组治疗后DAS28，差异具有统计学意义(

0.05)；③ MTX剂量与MTX-PGs浓度关系，10 mg、12.5 mg、15 mg各组MTX-PGs浓度分别为:92.0(88.0

96.0)ng/mL、112.0(103.0

115.0)ng/mL、127.5(102.0

153.8)ng/mL，三剂量组MTX-PGs浓度差异具有统计学意义(

0.05)；随着MTX剂量增加，MTX-PGs浓度也增高；10 mg组MTX-PGs浓度低于治疗有效时MTX-PGs浓度，差异具有统计学意义(

0.05)。

结论

MTX 12.5 mg/周可作为RA患者治疗的最佳初始有效剂量。

Abstract

Objective

To study the relation of methotrexate (MTX) dose with blood concentration of MTX polyglutamates (MTX-PGs) and clinical efficacy and explore the optimal initial dose of MTX for treatment of rheumatoid arthritis (RA).

Methods

We conducted a retrospective analysis of 165 RA patients receiving treatment in our hospital with MTX at the weekly oral dose of 10(

=67)

12.5(

=66) or 15 mg (

=32). The 28 joint disease activity scores (DAS28) were calculated before and after 8 weeks of MTX treatment. According to the European Union Anti-rheumatic Union (EULAR) criteria for efficacy evaluation

the clinical efficacy of the treatment was categorized into favorable responses (including significant and moderate responses) and nonresponse. High-performance liquid chromatography/tandem mass spectrometry (HPLC/MS/MS) assay was used to determine the blood concentration of MTX-PGs of the patients

and relations of MTX dose with the clinical efficacy

DAS28 after treatment and blood MTX-PGs concentration was analyzed.

Results

The patients taking MTX at the weekly dose of 10

12.5 and 15 mg showed total response rates of 37.31%

57.58%

and 56.25%

respectively

which was significantly lower in 10 mg group than in 12.5 mg group (

0.05). The median DAS28 after treatment was 3.92 (2.13-5.15)

2.80 (1.81-4.22)

and 2.96 (2.26-3.67) in the 10

12.5

and 15 mg groups

respectively

significantly highe

r in the 10 mg group than in 12.5 mg group (

0.05). The median blood concentrations of MTX-PGs in the 10

12.5

and 15 mg groups were 92.0 (88.0-96.0)

112.0 (103.0-115.0)

and 127.5 ng/mL (102.0-153.8 ng/mL)

respectively

showing significant differences among the 3 dose groups (

0.05). An increased MTX dose was associated with a higher MTX-PGs concentration in these patients. In 10 mg group

the mean blood concentration of MTX-PGs was 92.5±7.0 ng/mL

significantly lower than the documented concentration (92.5±7.0 ng/mL) required to produce a clinical response (

0.05).

Conclusion

MTX at the weekly oral dose of 12.5 mg can be the optimal initial dose for treatment of local RA patients in Chongqing.

关键词

Keywords

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