Smolen J S, Kalden J R, Scott D L, Rozman B, Kvien T K, Larsen A, Loew-Friedrich I, Oed C, Rosenburg R
Department of Internal Medicine III, University of Vienna, and Centre for Rheumatic Diseases, Lainz Hospital, Austria.
Lancet. 1999 Jan 23;353(9149):259-66. doi: 10.1016/s0140-6736(98)09403-3.
Phase II trials of leflunomide, an inhibitor of de-novo pyrimidine synthesis, have shown efficacy in rheumatoid arthritis. This double-blind randomised trial compared leflunomide with placebo and sulphasalazine in active rheumatoid arthritis.
358 patients were randomly assigned leflunomide (100 mg daily on days 1-3, then 20 mg daily), placebo, or sulphasalazine (0.5 g daily, titrated progressively to 2.0 g daily at week 4). The primary endpoints were tender and swollen joint counts and investigator's and patient's overall assessments. Analyses were by intention to treat.
The mean changes in the leflunomide, placebo, and sulphasalazine groups were -9.7, -4.3, and -8.1 for tender joint count; -7.2, -3.4, and -6.2 for swollen joint count; -1.1, -0.3, and -1.0 for physician's overall assessment; and -1.1, -0.4, and -1.1 for patient's overall assessment. Leflunomide and sulphasalazine were significantly superior to placebo (p=0.0001 for joint counts; p<0.001 for assessments). Radiographic disease progression was significantly slower with leflunomide and sulphasalazine than with placebo (p<0.01). Most common adverse events with leflunomide were diarrhoea (17%), nausea (10%), alopecia (8%), and rash (10%). Transiently abnormal liver function was seen in three leflunomide-group patients and five sulphasalazine-group patients. There were two cases of reversible agranulocytosis in the sulphasalazine group.
Leflunomide was more effective than placebo in treatment of rheumatoid arthritis and showed similar efficacy to sulphasalazine. Leflunomide was well tolerated. This drug may be a useful option as a disease-modifying antirheumatic drug.
来氟米特是一种新型嘧啶合成抑制剂，其II期试验已显示出对类风湿性关节炎的疗效。这项双盲随机试验比较了来氟米特与安慰剂及柳氮磺胺吡啶在活动性类风湿性关节炎中的作用。
358例患者被随机分配到来氟米特组（第1 - 3天每日100毫克，之后每日20毫克）、安慰剂组或柳氮磺胺吡啶组（每日0.5克，第4周逐渐滴定至每日2.0克）。主要终点为压痛和肿胀关节计数以及研究者和患者的总体评估。分析采用意向性治疗。
来氟米特组、安慰剂组和柳氮磺胺吡啶组的平均变化如下：压痛关节计数分别为-9.7、-4.3和-8.1；肿胀关节计数分别为-7.2、-3.4和-6.2；医生总体评估分别为-1.1、-0.3和-1.0；患者总体评估分别为-1.1、-0.4和-1.1。来氟米特和柳氮磺胺吡啶显著优于安慰剂（关节计数p = 0.0001；评估p < 0.001）。来氟米特和柳氮磺胺吡啶组的影像学疾病进展明显慢于安慰剂组（p < 0.01）。来氟米特最常见的不良事件为腹泻（17%）、恶心（10%）、脱发（8%）和皮疹（10%）。来氟米特组有3例患者肝功能短暂异常，柳氮磺胺吡啶组有5例。柳氮磺胺吡啶组有2例可逆性粒细胞缺乏症。
来氟米特在治疗类风湿性关节炎方面比安慰剂更有效，且与柳氮磺胺吡啶疗效相似。来氟米特耐受性良好。该药作为一种改善病情的抗风湿药物可能是一个有用的选择。
