Relationship between methotrexate dose and clinical efficacy for treatment of rheumatoid arthritis

Longquan HE; Ying SHI; Qinghua ZOU; Ping WAN; Bing ZHONG; Yongfei FANG

doi:10.16016/j.1000-5404.202003380

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Relationship between methotrexate dose and clinical efficacy for treatment of rheumatoid arthritis

Clinical Medicine | 更新时间：2026-01-09

- Relationship between methotrexate dose and clinical efficacy for treatment of rheumatoid arthritis
- Journal of Third Military Medical University Vol. 42, Issue 18, Pages: 1853-1858(2020)
- 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：
- 基金信息：
  
  the Health Technology Promotion Fund of Chongqing(2017jstg36)
- DOI：10.16016/j.1000-5404.202003380
  CLC： R593.22; R969.4; R979.12
- Received：30 March 2020，
  
  Revised：2020-05-22，
  
  Published：30 September 2020
- 稿件说明：
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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：

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

references

ALETAHA D, SMOLEN J S. Diagnosis and management of rheumatoid arthritis[J]. JAMA, 2018, 320(13): 1360. DOI: 10.1001/jama.2018.13103.

中华医学会风湿病学分会. 2018中国类风湿关节炎诊疗指南[J].中华内科杂志, 2018, 57(4): 242-251. DOI: 10.3760/cma.j.issn.0578-1426.2018.04.004.

Chinese Medical Association Rheumatology Branch. 2018 Chinese rheumatoid arthritis diagnosis and treatment guidelines[J]. Chin J Intern Med, 2018, 57(4): 242-251. DOI: 10.3760/cma.j.issn.0578-1426.2018.04.004.

PINCUS T, GIBSON K A, CASTREJÓN I. Update on methotrexate as the anchor drug for rheumatoid arthritis[J]. Bull Hosp Jt Dis, 2013, 71(Suppl 1): S9-S19.

SMOLEN J S, LANDEWÉ R, BIJLSMA J, et al . EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2016 update[J ] . Ann Rheum Dis, 2017, 76(6): 960-977. DOI: 10.1136/annrheumdis-2016-210715.

于萍, 任立敏, 王秀茹, 等.甲氨蝶呤在国人类风湿关节炎治疗中不良反应的调查及分析[J].中华风湿病学杂志, 2010, 14(8): 550-553. DOI: 10.3760/cma.j.issn.1007-7480.2010.08.0, 10.

YU P, REN L M, WANG X R, et al . Investigation and analysis of the adverse reactions of methotrexate in the treatment of human rheumatoid arthritis in China[J ] . Chin J Rheumatol, 2010, 14(8): 550-553. DOI: 10.3760/cma.j.issn.1007-7480.2010.08.0, 10.j. issn. 1007-7480.2010.08.0, 10.

STAMP L, ROBERTS R, KENNEDY M, et al . The use of low dose methotrexate in rheumatoid arthritis—are we entering a new era of therapeutic drug monitoring and pharmacogenomics?[J ] . Biomed Pharmacother, 2006, 60(10): 678-687. DOI: 10.1016/j.biopha.2006.09.007.

罗彦, 王志中, 王勇, 等.多聚谷氨酸化甲氨蝶呤浓度与类风湿关节炎疗效相关性研究[J].第三军医大学学报, J Thind Mil Med Univ, 2011, 33(5): 473-476. DOI: 1000-5404(2011)05-0473-04.

LUO Y, WANG Z Z, WANG Y, et al .Correlation of methotrexate polyglutamate concentration in erythrocyte with methotrexate efficacy in rheumatoid arthritis patients[J ] . J Third Mil Med Univ, 2011, 33(5): 473-476. DOI: 1000-5404(2011)05-0473-04.

ARNETT F C, EDWORTHY S M, BLOCH D A, et al . The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis[J ] . Arthritis Rheum, 1988, 31(3): 315-324. DOI: 10.1002/art.1780310302.

ALETAHA D, NEOGI T, SILMAN A J, et al . 2010 Rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative[J ] . Arthritis Rheum, 2010, 62(9): 2569-2581. DOI: 10.1002/art.27584.

DALRYMPLE J M, STAMP L K, O'DONNELL J L, et al . Pharmacokinetics of oral methotrexate in patients with rheumatoid arthritis[J ] . Arthritis Rheum, 2008, 58(11): 3299-3308. DOI: 10.1002/art.24034.

FRANSEN J, CREEMERS M C, VAN RIEL P L. Remission in rheumatoid arthritis: agreement of the disease activity score (DAS28) with the Ara preliminary remission criteria[J]. Rheumatology (Oxford), 2004, 43(10): 1252-1255. DOI: 10.1093/rheumatology/keh297.

VAN GESTEL A M, HAAGSMA C J, VAN RIEL P L. Validation of rheumatoid arthritis improvement criteria that include simplified joint counts[J]. Arthritis Rheum, 1998, 41(10): 1845-1850. DOI: 10.1002/1529-0131(199810)41: 10<1845: :AID-ART17>3.0.CO; 2-K.

VAN RIEL P L, RENSKERS L. The Disease Activity Score (DAS) and the Disease Activity Score using 28 joint counts (DAS28) in the management of rheumatoid arthritis[J]. Clin Exp Rheumatol, 2016, 34(5 Suppl 101): S40-S44.

JIN S Y, LI M T, FANG Y F, et al . Chinese registry of rheumatoid arthritis (CREDIT): Ⅱ. prevalence and risk factors of major comorbidities in Chinese patients with rheumatoid arthritis[J ] . Arthritis Res Ther, 2017, 19(1): 251. DOI: 10.1186/s13075-017-1457-z.

RUBINO F M. Separation methods for methotrexate, its structural analogues and metabolites[J]. J Chromatogr B Biomed Sci Appl, 2001, 764(1/2): 217-254. DOI: 10.1016/s0378-4347(01)00402-9.

DE ROTTE M C, DEN BOER E, DE JONG P H, et al . Methotrexate polyglutamates in erythrocytes are associated with lower disease activity in patients with rheumatoid arthritis[J ] . Ann Rheum Dis, 2015, 74(2): 408-414. DOI: 10.1136/annrheumdis-2013-203725.

中国医师协会风湿免疫科医师分会.甲氨蝶呤在风湿性疾病中的应用中国专家共识[J].中华内科杂志, 2018, 57(10): 719-722. DOI: 10.3760/cma.j.issn.0578- 1426.2018.10.005.

Chinese Medical Doctor Association of Rheumatology and Immunology Branch. Application of methotrexate in rheumatic diseases Chinese expert consensus[J]. Chin J Intern Med, 2018, 57 (10): 719-722. DOI: 10.3760/cma.j.issn.0578- 1426.2018.10.005.Issn.0578-1426.2018.10.005.

VAN EDE A E, LAAN R F, ROOD M J, et al . Effect of folic or folinic acid supplementation on the toxicity and efficacy of methotrexate in rheumatoid arthritis: A forty-eight-week, multicenter, randomized, double-blind, placebo-controlled study[J ] . Arthritis Rheum, 2001, 44(7): 1515-1524. DOI: 10.1002/1529-0131(200107)44: 7 < 1515: :AID-ART273 > 3.0.CO;2-7.

栗占国, 张奉春, 鲍春德.类风湿关节炎[M].北京:人民卫生出版社, 2009: 3-4.

LI Z G, ZHANG F C, BAO C D.Rheumatoid arthritis[M]. Beijing:People's Medical Publishing House, 2009: 3-4.

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