Application status of methotrexate in patients with rheumatoid arthritis
韩艺钧 1陈小莉 1李常虹 1赵金霞1
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作者信息
1. 北京大学第三医院风湿免疫科,北京 100191
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摘要
目的:分析甲氨蝶呤(methotrexate,MTX)在类风湿关节炎(rheumatoid arthritis,RA)患者中的应用现状.方法:纳入2022年1月1日至2023年11月31日于北京大学第三医院风湿免疫科诊治的RA患者,调查MTX的应用情况,包括起始剂量、最大剂量、目前用药情况、停药原因等,收集患者的临床信息和实验室数据,分析MTX应用与疾病控制情况之间的相关性.采用t检验、Mann-Whitney秩和检验、卡方检验和Fisher确切概率法和多因素回归分析进行统计学分析.结果:共纳入RA患者239例,其中女性201例,男性38例,平均年龄(54.5±14.3)岁.239例患者中,治疗达标(临床缓解或低疾病活动度)患者101例(42.2％),符合欧洲抗风湿病联盟(European League Against Rheumatism,EULAR)定义的难治性 RA 患者 26 例(10.9％),曾应用 MTX的比例为 84.1％(201/239 例),而目前仍规律应用者仅为39.7％(95/239例),且应用MTX的剂量普遍偏低,起始剂量为每周(9.5±3.0)mg,最大剂量中位数为每周15.0(10.0,15.0)mg,目前剂量为每周(12.4±2.7)mg.最常见的停药或减量原因为不良反应,主要包括肝功能异常、胃肠道不适及白细胞减少.目前规律应用MTX者与未用药者相比,治疗达标率更高(52.6％vs.35.4％,P＞0.05)、疾病活动度更低[28个关节计数的疾病活动评分(28-joint disease activity score,DAS28)-红细胞沉降率(erythrocyte sedimentation rate,ESR)评分(3.6±1.8)分 vs.(4.2±1.8)分,P＜0.05]、疼痛关节数更少[(4.8±8.3)个vs.(8.6±10.4)个,P＜0.05];而肿胀关节数、患者疼痛评分及总体评分、C反应蛋白、ESR等指标两组差异无统计学意义.与治疗未达标者相比,治疗达标者规律应用MTX的比例较高(48.5％vs.33.3％,P＜0.05),既往应用MTX的比例相当(84.2％vs.84.1％,P＞0.05);治疗达标者应用MTX的最大剂量较大(中位数每周 15.0 mg vs.13.7 mg,P＞0.05),目前剂量也较大[每周(12.9±2.5)mg vs.(11.8±2.8)mg,P＞0.05],而起始剂量两组相当[每周(9.6±2.8)mg vs.(9.5±3.1)mg,P＞0.05].难治性RA患者虽然既往应用MTX的比例较高(96.2％vs.82.6％,P＜0.05),但应用的最大剂量(中位数每周12.5 mg vs.15.0 mg,P＞0.05)和目前剂量均较小[每周(11.6±3.2)mg vs.(12.5±2.6)mg,P＞0.05].结论:RA患者中规律应用MTX的比例偏低,且药物剂量偏小;规律应用MTX的RA患者治疗达标率更高,疾病活动度更低;治疗达标者较未达标者目前应用MTX的比例高,最大剂量及目前剂量较大;难治性RA的患者应用MTX的最大剂量及维持剂量均偏低.RA患者中MTX的应用还有很大提升空间,通过提高RA患者MTX的使用率及用药剂量可能有助于改善RA患者的治疗达标率.
Abstract
Objective:To investigate the current status of methotrexate(MTX)application in rheuma-toid 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(EU-LAR)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 maxi-mum 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 curr-ent 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 ac-tivity.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.
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