Concomitant leflunomide therapy in patients with active rheumatoid arthritis despite stable doses of methotrexate - A randomized, double-blind, placebo-controlled trial
Concomitant leflunomide therapy in patients with active rheumatoid arthritis despite stable doses of methotrexate - A randomized, double-blind, placebo-controlled trial
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DOI：
10.7326/0003-4819-137-9-200211050-00007
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发表时间：
2002-11-05
影响因子：
39.2
通讯作者：
Bathon, JM
中科院分区：
文献类型：
--
作者：
Kremer, JM;Genovese, MC;Bathon, JM
背景资料：当与抗代谢药甲氨蝶呤联合使用时，病情缓解抗风湿药物可能会带来更大的益处。目的：评价来氟米特与安慰剂相比，在持续活动性类风湿关节炎患者中加入稳定剂量甲氨蝶呤治疗的疗效和安全性。设计：24周，多中心，随机，双盲，安慰剂对照试验。设置：美国和加拿大的20个中心。患者：持续性类风湿性关节炎的患者，如美国流变学学会（ACR）标准所定义的，尽管接受甲氨蝶呤至少6个月。干预：来氟米特或匹配的安慰剂添加到现有的甲氨蝶呤治疗，测量：主要疗效变量是在研究结束时达到ACR标准（ACR 20）的20%改善率。结果：来氟米特组和安慰剂组24周时分别有46.2%和19.5%的患者达到ACR 20标准（P < 0.001）。临床改善通过ACR 20缓解标准的单个组分的统计学显著平均变化来证明。两个治疗组的停药率相似（来氟米特组为23.1%，安慰剂组为24.8%），不良事件的总体发生率也相似（分别为89.2%和89.5%）。不良事件主要是轻度或moderate.Conclusions：来氟米特和甲氨蝶呤联合治疗活动性类风湿关节炎患者接受甲氨蝶呤治疗，来氟米特加甲氨蝶呤一般耐受性良好，可以安全地使用适当的肝酶和血液学监测提供了统计学显着的临床效益。
Background: Disease-modifying antirheumatic drugs may confer greater benefits when combined with the antimetabolite methotrexate.Objective: To evaluate the efficacy and safety of leflunomide versus placebo when added to ongoing, stable-dose methotrexate therapy in patients with persistently active rheumatoid arthritis.Design: 24-week, multicenter, randomized, double-blind, placebo-controlled trial.Setting: 20 centers in the United States and Canada.Patients: Patients with persistent rheumatoid arthritis, as defined by American College of Rheumatology (ACR) criteria, despite receiving methotrexate for at least 6 months.Intervention: Leflunomide or matching placebo added to existing methotrexate therapy,Measurements: The primary efficacy variable was the rate of achievement of 20% improvement in ACR criteria (ACR20) at the end of the study. The Health Assessment Questionnaire Disability Index was assessed at each visit and the Medical Outcomes Study 36-Item Short Form was completed as an end point analysis.Results: In the leflunomide and placebo groups, 46.2% and 19.5% of patients, respectively, met ACR20 criteria at 24 weeks (P < 0.001). Clinical improvement was demonstrated by statistically significant mean changes in individual components of the ACR20 response criteria. Discontinuation rates were similar in both treatment groups (23.1% in the leflunomide group and 24.8% in the placebo group), as were the overall incidences of adverse events (89.2% vs. 89.5%, respectively). Adverse events were predominantly mild or moderate.Conclusions: Combination therapy with leflunomide and methotrexate provides statistically significant clinical benefit in patients with active rheumatoid arthritis who are receiving methotrexate therapy, Leflunomide plus methotrexate is generally well tolerated and can be used safely with appropriate liver enzyme and hematologic monitoring.