Prakash A, Jarvis B
Adis International Limited, Mairangi Bay, Auckland, New Zealand.
Drugs. 1999 Dec;58(6):1137-64. doi: 10.2165/00003495-199958060-00010.
A77 1726, the active metabolite of leflunomide, is an immunomodulator which inhibits cell proliferation in activated lymphocytes in patients with active rheumatoid arthritis. Because A77 1726 has a long half-life (approximately 2 weeks), treatment with oral leflunomide is initiated with a loading dose of 100mg once daily for 3 days and continued with 20mg once daily. Results of large randomised, double-blind, multicentre trials of up to 24 months' duration have shown that leflunomide is significantly superior to placebo and at least as effective as sulfasalazine in improving primary outcome measures, such as tender joint counts, swollen joint counts and physicians' and patients' global assessment, in adult patients with active rheumatoid arthritis. Whereas improvement in all primary outcome measures with leflunomide was similar to or significantly less than that with methotrexate after 12 months, the efficacy of both agents was similar after 24 months. The therapeutic effect of leflunomide appears earlier (at 4 weeks) than that of sulfasalazine or methotrexate, and reduction from baseline values in functional disability was significantly greater with leflunomide than with sulfasalazine, methotrexate or placebo at end-point. Leflunomide was at least as effective as sulfasalazine or methotrexate in delaying the rate of radiological progression of disease. The most common adverse events reported in patients receiving leflunomide in randomised double-blind, placebo-controlled trials were diarrhoea (27%), respiratory infections (21%), nausea (13%), headache (13%), rash (12%), increased serum hepatic aminotransferases (10%), dyspepsia (10%) and alopecia (9%). Leflunomide was as well tolerated as sulfasalazine or methotrexate in clinical trials. Monitoring of serum hepatic enzyme levels is recommended in patients receiving leflunomide. The drug is not recommended in female patients who are or may become pregnant. Drug treatment should be discontinued, and hastened drug elimination procedure should be considered, in male patients wishing to father a child. 16 potential cases of pancytopenia and 9 cases of serious skin reactions have been associated with the use of leflunomide in 76,000 patients to date.
Leflunomide is a disease-modifying antirheumatic drug which reduces the signs and symptoms of inflammatory arthritis and delays the radiological progression of disease in adult patients with active rheumatoid arthritis. The drug appears to be as effective and as well tolerated as sulfasalazine or methotrexate, and represents a suitable alternative to these agents in adult patients with active rheumatoid arthritis. Benefits with leflunomide are evident within 4 weeks and efficacy is maintained for durations of up to 24 months.
来氟米特的活性代谢产物A77 1726是一种免疫调节剂，可抑制活动性类风湿关节炎患者活化淋巴细胞的增殖。由于A77 1726半衰期较长（约2周），口服来氟米特治疗开始时先给予负荷剂量，每日1次，每次100mg，连用3天，之后继续每日1次，每次20mg。长达24个月的大型随机、双盲、多中心试验结果表明，在改善主要观察指标方面，如来氟米特在改善成人活动性类风湿关节炎患者的压痛关节数、肿胀关节数以及医生和患者的整体评估等方面，明显优于安慰剂，且至少与柳氮磺胺吡啶疗效相当。虽然来氟米特在12个月时所有主要观察指标的改善情况与甲氨蝶呤相似或明显不如甲氨蝶呤，但在24个月时两种药物的疗效相似。来氟米特的治疗效果比柳氮磺胺吡啶或甲氨蝶呤出现得更早（4周时），且在终点时，来氟米特使功能残疾相对于基线值的降低幅度明显大于柳氮磺胺吡啶、甲氨蝶呤或安慰剂。来氟米特在延缓疾病放射学进展速度方面至少与柳氮磺胺吡啶或甲氨蝶呤一样有效。在随机双盲、安慰剂对照试验中接受来氟米特治疗的患者中报告的最常见不良事件为腹泻（27%）、呼吸道感染（21%）、恶心（13%）、头痛（13%）、皮疹（12%）、血清肝转氨酶升高（10%）、消化不良（10%）和脱发（9%）。在临床试验中来氟米特的耐受性与柳氮磺胺吡啶或甲氨蝶呤相当。建议接受来氟米特治疗的患者监测血清肝酶水平。不建议正在怀孕或可能怀孕的女性患者使用该药物。希望生育的男性患者应停用药物，并考虑采用加速药物清除程序。迄今为止，在76000例患者中使用来氟米特已出现16例可能的全血细胞减少病例和9例严重皮肤反应病例。
来氟米特是一种改善病情抗风湿药，可减轻成人活动性类风湿关节炎患者炎性关节炎的体征和症状，并延缓疾病的放射学进展。该药物似乎与柳氮磺胺吡啶或甲氨蝶呤一样有效且耐受性良好，是成人活动性类风湿关节炎患者这些药物的合适替代药物。来氟米特在4周内疗效明显，疗效可持续长达24个月。
