Rheumatology Unit, Azienda Ospedaliera Universitaria Senese, viale Bracci, 1, 53100, Siena, Italy.
Clin Rheumatol. 2010 May;29(5):517-24. doi: 10.1007/s10067-009-1349-y. Epub 2010 Jan 16.
To compare the efficacy and safety of leflunomide (LEF)-anti-TNF-alpha combination therapy to methotrexate (MTX)-anti-TNF-alpha combination therapy in a group of patients with active rheumatoid arthritis (RA). We have recruited 120 patients with RA with a high disease activity despite being treated with MTX (15 mg/week) or LEF (20 mg/die) for 3 months, without side effects. In each of these patients, therapy with either MTX or LEF was continued and randomly combined with an anti-TNF-alpha drug: etanercept, infliximab, or adalimumab. Patients were assessed at study entry and at 4, 12, and at 24 weeks. The efficacy endpoints included variations in the DAS28-ESR and the ACR20, ACR50, and ACR70 responses. At each visit, any side-effect was recorded. There were no statistically significant differences in the DAS28 variations and in the ACR responses between the two groups or among the six subgroups. The number of discontinuation due to the appearance of serious side effects was higher, but not statistically significant, in the LEF-anti-TNF-alpha group than in the MTX-anti-TNF-alpha group. Other adverse events that did not necessitate the discontinuation of therapy occurred much more frequently in patients treated with MTX than in those treated with LEF. Anti-TNF-alpha drugs can be used in combination not only with MTX, but also with LEF, with the same probability of achieving significant clinical improvement in RA patients and without a significantly greater risk of serious adverse events. In contrast, it seems that combination therapy with LEF-anti-TNF-alpha is more readily tolerated than combination therapy with MTX-anti-TNF-alpha.
比较来氟米特（LEF）-抗 TNF-α 联合治疗与甲氨蝶呤（MTX）-抗 TNF-α 联合治疗在一组患有活动性类风湿关节炎（RA）患者中的疗效和安全性。我们招募了 120 名 RA 患者，这些患者在接受 MTX（15mg/周）或 LEF（20mg/die）治疗 3 个月后疾病仍处于高度活跃状态，且无副作用。在这些患者中，继续使用 MTX 或 LEF 进行治疗，并随机联合使用抗 TNF-α 药物：依那西普、英夫利昔单抗或阿达木单抗。患者在研究入组时和第 4、12 和 24 周时进行评估。疗效终点包括 DAS28-ESR 和 ACR20、ACR50 和 ACR70 反应的变化。在每次就诊时，记录任何副作用。两组之间或六个亚组之间在 DAS28 变化和 ACR 反应方面没有统计学上的显著差异。由于出现严重副作用而停药的人数在 LEF-抗 TNF-α 组中较高，但无统计学意义高于 MTX-抗 TNF-α 组。其他不需要停药的不良事件在接受 MTX 治疗的患者中比接受 LEF 治疗的患者更频繁地发生。抗 TNF-α 药物不仅可以与 MTX 联合使用，也可以与 LEF 联合使用，RA 患者获得显著临床改善的可能性相同，且严重不良事件的风险无显著增加。相比之下，LEF-抗 TNF-α 联合治疗似乎比 MTX-抗 TNF-α 联合治疗更容易耐受。
