Application status of methotrexate in patients with rheumatoid arthritis

  • Yijun HAN ,
  • Xiaoli CHEN ,
  • Changhong LI ,
  • Jinxia ZHAO
Expand
  • Department of Rheumatology and Immunology, Peking University Third Hospital, Beijing 100191, China
ZHAO Jinxia, e-mail, zhao-jinxia@163.com

Received date: 2024-08-08

  Online published: 2024-12-18

Supported by

the Clinical Cohort Construction Program of Peking University Third Hospital(BYSYDL2022017)

Copyright

, 2024, All rights reserved, without authorization

Abstract

Objective: To investigate the current status of methotrexate (MTX) application in rheumatoid arthritis (RA) patients. Methods: The clinical and laboratory data of RA patients who attended in the Department of Rheumatology and Immunology of Peking University Third Hospital from January 1, 2022 to November 31, 2023 were collected retrospectively. In order to figure out the relationship between MTX use and RA disease control, we recorded information including the starting dose, maximum dose, current dose, reasons of discontinuation of MTX, etc. The t test, Mann-Whitney U test, Chi-square test, Fisher' s exact probability and multivariable Logistic regression were used for analysis. Results: A total of 239 RA patients were enrolled, including 201 females and 38 males with a mean age of (54.5±14.3) years. Among them, 101 patients reached the therapeutic target [clinical remission or low disease activity assessed by 28-joint disease activity score (DAS28)-erythrocyte sedimentation rate (ESR)], accounting for 42.2% of the RA patients. Twenty-six patients met the European League Against Rheumatism (EULAR) definition of difficult-to-treat (D2T) RA, accounting for 10.9% of RA patients. The proportion of the RA patients who had ever used MTX was 84. 1%, and those who were currently on it accounted for only 39.7%. The MTX dose was generally low, with a starting dose of (9.5±3.0) mg/week, the maximum dose of 15.0 (10.0, 15.0) mg/week, and the current dose being (12.4±2.7) mg/week. The most common reasons for MTX dose reduction or discontinuation were adverse reactions, mainly including abnormalities of hepatic function, gastrointestinal discomfort, leucopenia, etc. Those who were currently on MTX had a higher rate of treatment to target (52.6% vs. 35.4%, P>0.05), lower disease activity score (DAS28-ESR, 3.6±1.8 vs. 4.2±1.8, P < 0.05), and fewer tender joint counts (4.8±8.3 vs. 8.6±10.4, P < 0.05) as compared with those who were not taking the drug, while swollen joint count, pain visual analog score and patient' s global score, C-reactive protein (CRP) level and ESR level were not significantly different between the two groups. Compared with those who did not reach the target of treatment, those who did had a higher rate of current MTX application (48.5% vs. 33.3%, P < 0.05), but the history of MTX did not differ between the two groups (84.2% vs. 84.1%, P>0.05). The maximum dose of MTX (median 15.0 mg/week vs. 13.7 mg/week, P>0.05) and the current dose [(12.9±2.5) mg/week vs. (11.8±2.8) mg/week, P>0.05] was higher in those who achieved the target, while the starting dose [(9.6±2.8) mg/week vs. (9.5±3.1) mg/week, P>0.05] and the rate of prior MTX (84.2% vs. 83.3%, P>0.05) was comparable between the two groups. The D2T RA patients had a higher rate of previous MTX use (96.2% vs. 82.6%, P < 0.05) and a higher starting dose [(11.6±4.3) mg/week vs. (9.8±2.7) mg/week, P>0.05], while the maximum dose (median 12.5 mg/week vs. 15.0 mg/week, P>0.05) and the current dose were both lower [(11.6±3.2) mg/week vs. (12.5±2.6) mg/week, P>0.05] than the non-D2T RA patients. Conclusion: The proportion of regular use of MTX among RA patients was low and the dose was generally small. The RA patients with regular use of MTX had a higher rate of achieving treatment target and lower disease activity. Those who achieved the target had a higher rate of current MTX use, higher maximum and current doses than those who did not. The D2T RA patients had lower maximum and current doses of MTX than the non-D2T RA patients. Therefore, increasing the usage and dosage of MTX in RA patients may help to improve the rate of achieving treatment targets.

Cite this article

Yijun HAN , Xiaoli CHEN , Changhong LI , Jinxia ZHAO . Application status of methotrexate in patients with rheumatoid arthritis[J]. Journal of Peking University(Health Sciences), 2024 , 56(6) : 994 -1000 . DOI: 10.19723/j.issn.1671-167X.2024.06.008

References

1 Smolen JS , Landewé RBM , Bergstra SA , et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2022 update[J]. Ann Rheum Dis, 2023, 82 (1): 3- 18.
2 耿研, 谢希, 王昱, 等. 类风湿关节炎诊疗规范[J]. 中华内科杂志, 2022, 61 (1): 51- 59.
3 Yu C , Li M , Duan X , et al. Chinese registry of rheumatoid arthritis (CREDIT): Ⅰ. Introduction and prevalence of remission in Chinese patients with rheumatoid arthritis[J]. Clin Exp Rheumatol, 2018, 36 (5): 836- 840.
4 Sun X , Li R , Cai Y , et al. Clinical remission of rheumatoid arthritis in a multicenter real-world study in Asia-Pacific region[J]. Lancet Reg Health West Pac, 2021, 15, 100240.
5 Sokka T , Kautiainen H , Toloza S , et al. QUEST-RA: Quantitative clinical assessment of patients with rheumatoid arthritis seen in standard rheumatology care in 15 countries[J]. Ann Rheum Dis, 2007, 66 (11): 1491- 1496.
6 田新平, 李梦涛, 曾小峰. 我国类风湿关节炎诊治现状与挑战: 来自中国类风湿关节炎2019年年度报告[J]. 中华内科杂志, 2021, 60 (7): 593- 598.
7 Aletaha D , Neogi T , Silman AJ , et al. 2010 rheumatoid arthritis classification criteria: An American College of Rheumatology/European League Against Rheumatism collaborative initiative[J]. Ann Rheum Dis, 2010, 69 (9): 1580- 1588.
8 Nagy G , Roodenrijs NMT , Welsing PM , et al. EULAR definition of difficult-to-treat rheumatoid arthritis[J]. Ann Rheum Dis, 2021, 80 (1): 31- 35.
9 Kearsley-Fleet L , Davies R , de Cock D , et al. Biologic refractory disease in rheumatoid arthritis: Results from the British Society for Rheumatology Biologics Register for rheumatoid arthritis[J]. Ann Rheum Dis, 2018, 77 (10): 1405- 1412.
10 Roodenrijs NMT , van der Goes MC , Welsing PMJ , et al. Difficult-to-treat rheumatoid arthritis: Contributing factors and burden of disease[J]. Rheumatology (Oxford), 2021, 60 (8): 3778- 3788.
11 Valerio V , Kwok M , Loewen H , et al. Systematic review of recommendations on the use of methotrexate in rheumatoid arthritis[J]. Clin Rheumatol, 2021, 40 (4): 1259- 1271.
12 代丽怡, 赵金霞. 甲氨蝶呤单药治疗类风湿关节炎的再认识[J]. 中华医学杂志, 2022, 102 (37): 2909- 2913.
13 Wang W , Zhou H , Liu L . Side effects of methotrexate therapy for rheumatoid arthritis: A systematic review[J]. Eur J Med Chem, 2018, 158, 502- 516.
14 Friedman B , Cronstein B . Methotrexate mechanism in treatment of rheumatoid arthritis[J]. Joint Bone Spine, 2019, 86 (3): 301- 307.
15 Smolen JS , Aletaha D , McInnes IB . Rheumatoid arthritis[J]. Lancet, 2016, 388 (10055): 2023- 2038.
16 Brown PM , Pratt AG , Isaacs JD . Mechanism of action of methotrexate in rheumatoid arthritis, and the search for biomarkers[J]. Nat Rev Rheumatol, 2016, 12 (12): 731- 742.
17 Ling S , Bluett J , Barton A . Prediction of response to methotrexate in rheumatoid arthritis[J]. Expert Rev Clin Immunol, 2018, 14 (5): 419- 429.
18 Gehringer CK , Martin GP , Hyrich K , et al. Developing and externally validating multinomial prediction models for methotrexate treatment outcomes in patients with rheumatoid arthritis: Results from an international collaboration[J]. J Clin Epidemiol, 2024, 166, 111239.
19 Saevarsdottir S , Wedren S , Seddighzadeh M , et al. Patients with early rheumatoid arthritis who smoke are less likely to respond to treatment with methotrexate and tumor necrosis factor inhibitors: Observations from the Epidemiological Investigation of Rheumatoid Arthritis and the Swedish Rheumatology Register cohorts[J]. Arthritis Rheum, 2011, 63 (1): 26- 36.
20 Sysojev A? , Saevarsdottir S , Diaz-Gallo LM , et al. Genome-wide investigation of persistence with methotrexate treatment in early rheumatoid arthritis[J]. Rheumatology (Oxford), 2024, 63 (5): 1221- 1229.
21 Palmowski A , Strehl C , Pfeiffenberger M , et al. Identification of gene expression biomarkers to predict clinical response to methotrexate in patients with rheumatoid arthritis[J]. Clin Rheumatol, 2024, 43 (1): 511- 519.
22 Jenko B , Tomsic M , Jekic B , et al. Clinical pharmacogenetic models of treatment response to methotrexate monotherapy in slovenian and serbian rheumatoid arthritis patients: Differences in patient ' s management may preclude generalization of the models[J]. Front Pharmacol, 2018, 9, 20.
23 Ally MM , Hodkinson B , Meyer PW , et al. Circulating anti-citrullinated peptide antibodies, cytokines and genotype as biomarkers of response to disease-modifying antirheumatic drug therapy in early rheumatoid arthritis[J]. BMC Musculoskelet Disord, 2015, 16, 130.
Outlines

/