[1]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.
 HE Longquan,SHI Ying,ZOU Qinghua,et al.Relationship between methotrexate dose and clinical efficacy for treatment of rheumatoid arthritis[J].J Third Mil Med Univ,2020,42(18):1853-1858.
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《第三军医大学学报》[ISSN:1000-5404/CN:51-1095/R]

卷:
42卷
期数:
2020年第18期
页码:
1853-1858
栏目:
临床医学
出版日期:
2020-09-30

文章信息/Info

Title:
Relationship between methotrexate dose and clinical efficacy for treatment of rheumatoid arthritis
作者:
贺龙全石颖邹庆华万萍钟兵方勇飞
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
Author(s):
HE Longquan SHI Ying ZOU Qinghua WAN Ping ZHONG Bing FANG Yongfei

Department of Traditional Chinese Medicine and Rheumatology, First Affiliated Hospital, Army Medical University (Third Military Medical University), Chongqing, 400038, China

关键词:
类风湿关节炎甲氨蝶呤多聚谷氨酸化甲氨蝶呤
Keywords:
rheumatoid arthritis methotrexate polyglutamate methotrexates
分类号:
R593.22;R969.4;R979.12
文献标志码:
A
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(P<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(P<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(P<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(P<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:

ObjectiveTo 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). MethodsWe conducted a retrospective analysis of 165 RA patients receiving treatment in our hospital with MTX at the weekly oral dose of 10(n=67), 12.5(n=66) or 15 mg (n=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. ResultsThe 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 (P<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 higher in the 10 mg group than in 12.5 mg group (P<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 (P<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 (P<0.05). ConclusionMTX at the weekly oral dose of 12.5 mg can be the optimal initial dose for treatment of local RA patients in Chongqing.

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更新日期/Last Update: 2020-09-22