A comparison of the efficacy and safety of leflunomide and methotrexate for the treatment of rheumatoid arthritis
A comparison of the efficacy and safety of leflunomide and methotrexate for the treatment of rheumatoid arthritis
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DOI：
10.1093/rheumatology/39.6.655
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发表时间：
2000-06-01
期刊：
影响因子：
5.5
通讯作者：
Loew-Friedrich, I
中科院分区：
文献类型：
--
作者：
Emery, P;Breedveld, FC;Loew-Friedrich, I
Objective.比较来氟米特与甲氨蝶呤治疗类风湿关节炎（RA）的临床疗效和安全性。在这项多中心、双盲试验中，999例活动性RA受试者随机接受来氟米特（n = 501;负荷剂量100 mg/天，持续3天，维持剂量20 mg/天）或甲氨蝶呤（n = 498; 10-15 mg/周）治疗52周。1年后，受试者可以选择继续接受第二年的双盲治疗。主要终点是压痛和肿胀关节计数以及医生和患者的总体评估。分析的是意向治疗组。1年后，来氟米特和甲氨蝶呤组的压痛关节计数平均变化分别为-8.3和-9.7;肿胀关节计数平均变化分别为-6.8和-9.0;医生总体评估平均变化分别为-0.9和-1.2;患者总体评估平均变化分别为-0.9和-1.2;红细胞沉降率平均变化分别为-14.4和-28.2。甲氨蝶呤的改善明显大于来氟米特。治疗第二年后没有进一步改善，两种治疗在压痛关节计数和患者总体评估方面的差异消失。在治疗的第一年期间，两种药物均观察到较小且同等程度的放射学评估的疾病进展。2年后，甲氨蝶呤组的疾病进展明显减少。两组中最常见的治疗相关不良事件为腹泻、恶心、脱发、皮疹、头痛和血浆肝酶水平升高。2年以上21名接受甲氨蝶呤的受试者因血浆肝酶升高而退出，8名接受来氟米特的受试者退出。在接受来氟米特治疗的受试者中，甲氨蝶呤组发生了2例药物相关性肺部死亡，而无药物相关性死亡。来氟米特和甲氨蝶呤都是有效的长期治疗RA。在使用的剂量下，在治疗的第一年观察到甲氨蝶呤比来氟米特有一些临床益处。这种益处必须与这种药物在不补充叶酸的情况下使用时的潜在毒性进行权衡。
Objective. To compare the clinical efficacy and safety of leflunomide and methotrexate for the treatment of rheumatoid arthritis (RA).Methods. In this multicentre, double-blind trial, 999 subjects with active RA were randomized to leflunomide (n = 501; loading dose 100 mg/day for 3 days, maintenance dose 20 mg/day) or methotrexate (n = 498; 10-15 mg/week) for 52 weeks. After 1 yr the subjects could choose to stay for a second year of double-blind treatment. The primary end-points were tender and swollen joint counts and overall physician and patient assessments. Analyses were of the intent-to-treat group.Results. After 1 yr, the mean changes in the leflunomide and methotrexate groups, respectively, were -8.3 and -9.7 for tender joint count; -6.8 and -9.0 for swollen joint count; -0.9 and -1.2 for physician global assessment; -0.9 and -1.2 for patient global assessment; -14.4 and -28.2 for erythrocyte sedimentation rate. Improvements seen with methotrexate were significantly greater than those with leflunomide. No further improvement occurred after the second year of treatment and the distinction between the two treatments in terms of tender joint count and patient global assessment was lost. During the first year of treatment, a small and equivalent degree of radiographically assessed disease progression was seen with both drugs. After 2 yr, disease progression was significantly less with methotrexate. The most common treatment-related adverse events in both groups were diarrhoea, nausea, alopecia, rash, headache, and elevated plasma liver enzyme levels. Over 2 yr. 21 subjects receiving methotrexate were withdrawn due to elevated plasma liver enzymes rs eight subjects taking leflunomide. Two drug-related deaths from pulmonary causes were recorded with methotrexate ps no drug-related deaths among the subjects receiving leflunomide.Conclusions. Both leflunomide and methotrexate are efficacious for prolonged treatment of RA. At the doses used, some clinical benefit of methotrexate over leflunomide was observed in the first year of treatment. This benefit must be weighed against the potential toxicity of this drug when used without folate supplementation.