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[甲氨蝶呤在类风湿关节炎患者中的应用现状]

[Application status of methotrexate in patients with rheumatoid arthritis].

作者信息

Han Yijun, Chen Xiaoli, Li Changhong, Zhao Jinxia

机构信息

Department of Rheumatology and Immunology, Peking University Third Hospital, Beijing 100191, China.

出版信息

Beijing Da Xue Xue Bao Yi Xue Ban. 2024 Dec 18;56(6):994-1000. doi: 10.19723/j.issn.1671-167X.2024.06.008.

DOI:10.19723/j.issn.1671-167X.2024.06.008
PMID:39690760
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11652998/
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, . The test, Mann-Whitney 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, Those who were currently on MTX had a higher rate of treatment to target (52.6% 35.4%, 0.05), lower disease activity score (DAS28-ESR, 3.6±1.8 4.2±1.8, < 0.05), and fewer tender joint counts (4.8±8.3 8.6±10.4, < 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% 33.3%, < 0.05), but the history of MTX did not differ between the two groups (84.2% 84.1%, >0.05). The maximum dose of MTX (median 15.0 mg/week 13.7 mg/week, >0.05) and the current dose [(12.9±2.5) mg/week (11.8±2.8) mg/week, >0.05] was higher in those who achieved the target, while the starting dose [(9.6±2.8) mg/week (9.5±3.1) mg/week, >0.05] and the rate of prior MTX (84.2% 83.3%, >0.05) was comparable between the two groups. The D2T RA patients had a higher rate of previous MTX use (96.2% 82.6%, < 0.05) and a higher starting dose [(11.6±4.3) mg/week (9.8±2.7) mg/week, >0.05], while the maximum dose (median 12.5 mg/week 15.0 mg/week, >0.05) and the current dose were both lower [(11.6±3.2) mg/week (12.5±2.6) mg/week, >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.

摘要

目的

探讨甲氨蝶呤(MTX)在类风湿关节炎(RA)患者中的应用现状。

方法

回顾性收集2022年1月1日至2023年11月31日在北京大学第三医院风湿免疫科就诊的RA患者的临床和实验室资料。为明确MTX使用与RA疾病控制之间的关系,我们记录了包括起始剂量、最大剂量、当前剂量、MTX停药原因等信息。采用t检验、曼-惠特尼U检验、卡方检验、Fisher确切概率法和多变量Logistic回归进行分析。

结果

共纳入239例RA患者,其中女性201例,男性38例,平均年龄(54.5±14.3)岁。其中,101例患者达到治疗目标[根据28个关节疾病活动评分(DAS28)-红细胞沉降率(ESR)评估为临床缓解或低疾病活动度],占RA患者的42.2%。26例患者符合欧洲抗风湿病联盟(EULAR)难治性(D2T)RA的定义,占RA患者的10.9%。曾使用MTX的RA患者比例为84.1%,而目前正在使用的患者仅占39.7%。MTX剂量普遍较低,起始剂量为(9.5±3.0)mg/周,最大剂量为15.0(10.0,15.0)mg/周,当前剂量为(12.4±2.7)mg/周。MTX剂量减少或停药的最常见原因是不良反应,主要包括肝功能异常、胃肠道不适、白细胞减少等。与未服用该药的患者相比,目前正在使用MTX的患者达到治疗目标的比例更高(52.6%对35.4%,P<0.05),疾病活动评分(DAS28-ESR)更低(3.6±1.8对4.2±1.8,P<0.05),压痛关节数更少(4.8±8.3对8.6±10.4,P<0.05),而两组间肿胀关节数、疼痛视觉模拟评分、患者整体评分、C反应蛋白(CRP)水平和ESR水平无显著差异。与未达到治疗目标的患者相比,达到目标的患者当前MTX应用率更高(48.5%对33.3%,P<0.05),但两组间MTX使用史无差异(84.2%对84.1%,P>0.05)。达到目标的患者MTX最大剂量(中位数15.0 mg/周对13.7 mg/周,P>0.05)和当前剂量[(12.9±2.5)mg/周对(11.8±2.8)mg/周,P>0.05]更高,而起始剂量[(9.6±2.8)mg/周对(9.5±3.1)mg/周,P>0.05]和既往MTX使用率(84.2%对83.3%,P>0.05)两组间相当。D2T RA患者既往MTX使用率更高(96.2%对82.6%,P<0.05),起始剂量更高[(11.6±4.3)mg/周对(9.8±2.7)mg/周,P>0.05],而最大剂量(中位数12.5 mg/周对15.0 mg/周,P>0.05)和当前剂量均低于非D2T RA患者[(11.6±3.2)mg/周对(12.5±2.6)mg/周,P>0.05]。

结论

RA患者中MTX规律使用比例低且剂量普遍较小。规律使用MTX的RA患者达到治疗目标的比例更高,疾病活动度更低。达到目标的患者当前MTX使用率更高,最大剂量和当前剂量高于未达到目标的患者。D2T RA患者MTX的最大剂量和当前剂量低于非D2T RA患者。因此,增加RA患者MTX的使用量和剂量可能有助于提高治疗目标达成率。

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本文引用的文献

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Identification of gene expression biomarkers to predict clinical response to methotrexate in patients with rheumatoid arthritis.鉴定基因表达生物标志物以预测类风湿关节炎患者对甲氨蝶呤的临床反应。
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Zhonghua Yi Xue Za Zhi. 2022 Oct 11;102(37):2909-2913. doi: 10.3760/cma.j.cn112137-20220224-00394.
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