Osiri Manathip, Shea Beverley, Robinson Vivian, Suarez-Almazor Maria, Strand Vibeke, Tugwell Peter, Wells George
Department of Medicine, Faculty of Medicine, Chulalongkorn University Hospital, Bangkok, Thailand.
J Rheumatol. 2003 Jun;30(6):1182-90.
To systematically review the evidence from clinical trials on the efficacy and toxicity of leflunomide for the treatment of active rheumatoid arthritis (RA).
We searched Medline, Embase, Current Contents, and the Cochrane Controlled Trial Register for human randomized controlled trials (RCT) and controlled clinical trials up to December 2001. We also hand-searched reference lists and conference proceedings and consulted content experts. Relative benefit (RB), and weighted mean differences or standardized mean differences with their 95% confidence interval (95% CI) were calculated.
Six RCT totaling 2044 patients with RA were included in this review. Using specific criteria, all trials were considered of high methodological quality. Leflunomide improved the ACR20 response rate roughly 2 times over placebo both at 6 months (RB = 1.93, 95% CI 1.51, 2.47) and at 12 months (RB = 1.99, 95% CI 1.42, 2.77). Other clinical outcomes of disease activity and function and radiological scores were also significantly better for leflunomide patients than those taking placebo. No significant differences for most of the outcomes were observed between leflunomide and sulfasalazine (SSZ) or methotrexate (MTX). Adverse events were more common in the leflunomide group, but withdrawal rates were fewer than for placebo. Overall, withdrawal rates and adverse events in the leflunomide group were not different from SSZ or MTX.
Leflunomide improves all clinical outcomes and delays radiographic progression at 6 and 12 months of RA treatment compared to placebo. Its efficacy and adverse events at 2 years of treatment are comparable to SSZ and MTX. Longterm efficacy and toxicity remain to be established.
系统评价来氟米特治疗活动性类风湿关节炎（RA）的疗效和毒性的临床试验证据。
检索了Medline、Embase、《现刊目次》和Cochrane对照试验注册库，以查找截至2001年12月的人类随机对照试验（RCT）和对照临床试验。我们还手工检索了参考文献列表和会议论文集，并咨询了内容专家。计算了相对效益（RB）以及加权均数差值或标准化均数差值及其95%置信区间（95%CI）。
本综述纳入了6项RCT，共2044例RA患者。根据特定标准，所有试验均被认为具有较高的方法学质量。来氟米特在6个月时（RB = 1.93，95%CI 1.51，2.47）和12个月时（RB = 1.99，95%CI 1.42，2.77）使ACR20缓解率提高约为安慰剂的2倍。来氟米特治疗的患者在疾病活动、功能和放射学评分等其他临床结局方面也显著优于服用安慰剂的患者。来氟米特与柳氮磺胺吡啶（SSZ）或甲氨蝶呤（MTX）在大多数结局方面未观察到显著差异。来氟米特组不良事件更常见，但停药率低于安慰剂组。总体而言，来氟米特组的停药率和不良事件与SSZ或MTX无差异。
与安慰剂相比，来氟米特在RA治疗6个月和12个月时可改善所有临床结局并延缓放射学进展。其2年治疗时的疗效和不良事件与SSZ和MTX相当。长期疗效和毒性仍有待确定。
