Factors associated with toxicity, final dose, and efficacy of methotrexate in patients with rheumatoid arthritis
Factors associated with toxicity, final dose, and efficacy of methotrexate in patients with rheumatoid arthritis
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DOI：
10.1136/ard.62.5.423
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发表时间：
2003-05-01
影响因子：
27.4
通讯作者：
Laan, RFJM
中科院分区：
文献类型：
--
作者：
Hoekstra, M;van Ede, AE;Laan, RFJM
目的：目的：探讨甲氨蝶呤（MTX）治疗类风湿关节炎（RA）的毒副作用、最终剂量和疗效的相关因素。方法：采用411例RA患者进行为期48周的随机临床试验，比较叶酸和安慰剂治疗RA的疗效。采用Logistic回归分析研究基线变量与各种依赖因素之间的关系，包括肝毒性（丙氨酸氨基转移酶大于或等于正常值上限的3倍），MTX停药，MTX最终剂量大于或等于15 mg/周，MTX efficence.Results：MTX治疗中添加叶酸与肝毒性的缺乏密切相关。其次，高体重指数与肝毒性的发生有关。既往胃肠道（GI）事件和年龄较小与不良事件腹泻相关。肝毒性和胃肠道不良事件是MTX停药的主要原因，而MTX停药又与未补充叶酸、体重指数、既往胃肠道事件和女性相关。肾功能（肌酐清除率大于或等于50 ml/min）与毒性无关。MTX的最终剂量大于或等于15 mg/周与叶酸补充和既往无胃肠道事件有关。MTX治疗的疗效与基线时疾病活动度低、男性、使用非甾体类抗炎药（NSAIDs）和肌酐清除率较低相关。结论：MTX毒性、最终剂量和疗效受叶酸补充剂的影响。预测MTX治疗结果的基线特征主要是既往GI事件、体重指数、性别、NSAID的使用和肌酐清除率。
Objective: To study factors associated with toxicity, final dose, and efficacy of methotrexate (MTX) in patients with rheumatoid arthritis (RA).Methods: Data were used from a randomised clinical 48 week trial on 411 patients with RA all treated with MTX, comparing folates and placebo. Logistic regression was used to study the relation between baseline variables and various dependent factors, including hepatotoxicity (alanine aminotransferase greater than or equal to3xupper limit of normal), MTX withdrawal, final MTX dose greater than or equal to15 mg/week, and MTX efficacy.Results: Addition of folates to MTX treatment was strongly related to the lack of hepatotoxicity. Next to this, high body mass index was related to the occurrence of hepatotoxicity. Prior gastrointestinal (GI) events and younger age were related to the adverse event, diarrhoea. Hepatotoxicity and GI adverse events were the main reason for MTX withdrawal, which in turn was associated with the absence of folate supplementation, body mass index, prior GI events, and female sex. Renal function (creatinine clearance greater than or equal to50 ml/min) was not associated with toxicity. Reaching a final dose of MTX of greater than or equal to15 mg/week was related to folate supplementation and the absence of prior GI events. Efficacy of MTX treatment was associated with low disease activity at baseline, male sex, use of non-steroidal anti-inflammatory drugs (NSAIDs), and lower creatinine clearance.Conclusions: MTX toxicity, final dose, and efficacy are influenced by folate supplementation. Baseline characteristics predicting the outcome of MTX treatment are mainly prior GI events, body mass index, sex, use of NSAIDs, and creatinine clearance.