Aletaha D, Stamm T, Kapral T, Eberl G, Grisar J, Machold K P, Smolen J S
Division of Rheumatology, Department of Internal Medicine III, University of Vienna, Austria.
Ann Rheum Dis. 2003 Oct;62(10):944-51. doi: 10.1136/ard.62.10.944.
To determine the survival and clinical effectiveness of leflunomide (LEF) compared with methotrexate (MTX) and sulfasalazine (SSZ) for RA in an observational study.
An observational database of 1088 patients and 5141 patient years of DMARD treatment (2680 courses) from two academic hospitals was filtered for treatment with LEF, MTX, and SSZ. LEF treatment groups were matched for patients' age, baseline ESR, number of previous DMARDs, and hospital cohort with MTX and SSZ treatment groups. For these treatments, Kaplan-Meier analyses of time until the drug was discontinued (drug "survival"), and the effectiveness and safety of continuation of treatment, were performed. The change in disease activity markers (CRP, ESR) was compared between the groups.
The median dose during the study increased from 10 to 15 mg MTX/week and from 1.5 to 2.0 g SSZ/day. Matched survival analysis showed better retention rates for MTX (mean (SEM) survival 28 (1) months) than for LEF (20 (1) months; p=0.001), whereas retention rates of SSZ (23 (1) months) were similar to those of LEF (p=NS). Treatments were stopped earlier because of adverse events (AEs, 3 months) than because of ineffectiveness (IE, 10 months; p<0.001). LEF and MTX were less likely to be stopped because of AEs than SSZ. LEF courses were stopped earlier for AEs (p<0.001) than MTX.
Current dosing strategies should be re-evaluated, and coping strategies for common AEs should be investigated. This will be necessary to achieve better drug retention of LEF. At present, MTX continues to be the most effective drug in clinical practice.
在一项观察性研究中确定来氟米特（LEF）与甲氨蝶呤（MTX）和柳氮磺胺吡啶（SSZ）相比治疗类风湿关节炎（RA）的生存率和临床疗效。
从两家学术医院筛选出一个包含1088例患者和5141患者年的改善病情抗风湿药（DMARD）治疗（2680疗程）的观察性数据库，以获取接受LEF、MTX和SSZ治疗的患者。将LEF治疗组与MTX和SSZ治疗组在患者年龄、基线血沉（ESR）、既往DMARDs数量以及医院队列方面进行匹配。对这些治疗进行Kaplan-Meier分析，以确定药物停用前的时间（药物“生存期”）以及继续治疗的有效性和安全性。比较各组间疾病活动标志物（CRP、ESR）的变化。
研究期间MTX的中位剂量从每周10毫克增加到15毫克，SSZ从每日1.5克增加到2.0克。匹配生存分析显示，MTX的保留率（平均（标准误）生存期28（1）个月）优于LEF（20（1）个月；p = 0.001），而SSZ的保留率（23（1）个月）与LEF相似（p = 无显著性差异）。治疗因不良事件（AE，3个月）而停用的时间早于因无效（IE，10个月；p < 0.001）。与SSZ相比，LEF和MTX因AE而停用的可能性较小。LEF疗程因AE而停用的时间（p < 0.001）早于MTX。
应重新评估当前的给药策略，并研究常见AE的应对策略。这对于提高LEF的药物保留率是必要的。目前，MTX在临床实践中仍然是最有效的药物。
