Int J Immunopathol Pharmacol. 2011 Jan-Mar;24(1):269-74. doi: 10.1177/039463201102400136.
Several smaller retrospective case series have concluded that leflunomide (LEF) in combination with anti-TNF-alpha blocking agents appears to be effective and safe. Prospective case series and cohort studies have generally confirmed the efficacy of this combination. Overall, there is currently no evidence from controlled trials that an anti-TNF-alpha combination with LEF is as effective as an anti-TNF-alpha combination with methotrexate (MTX). We compared the effectiveness and safety of a therapeutic regimen associating subcutaneous anti-TNF-alpha agents, etanercept (ETN) and adalimumab (ADA), with leflunomide (LEF) or methotrexate (MTX), in a two year open-label study performed in clinical practice. We evaluated 96 patients with active rheumatoid arthritis undergoing therapy with ADA at the dose of 40 mg every other week, or with ETN at the dose of 50 mg/week for two years added to prednisolone (PDN) at the mean dose of 5.2±2.6 mg/day. Fifty-four of these patients were also undergoing therapy with MTX at the mean dose of 11.7±2.6 mg/week, while 42 patients were undergoing therapy with LEF at the daily dose of 20 mg. At 12 months, the analysis of variance showed an improvement of DAS28 in both groups (p<0.001), with a reduction in 33.3% of the patients in treatment with LEF and in 51.8% of the patients in treatment with MTX (p = 0.20). At 18 months, improvement was present in 33.3% of the patients in the LEF group and in 81.5% of the patients in the MTX group (p=0.001). This improvement seems to be independent of the anti-TNF-alpha agent, even if MTX produces the highest DAS28 reduction when used in association with ETN (p<0.078). We found no difference in drug discontinuation rates or in effectiveness measures between anti-TNFalpha+MTX and anti-TNFalpha+LEF. Our data showed a greater reduction of DAS28 in the MTX group and, in combination with ETN, better results after two years of therapy.
几项较小的回顾性病例系列研究得出结论，来氟米特（LEF）联合抗 TNF-α 阻断剂似乎有效且安全。前瞻性病例系列和队列研究普遍证实了这种联合治疗的疗效。总体而言，目前尚无对照试验证据表明，LEF 联合抗 TNF-α 药物与 MTX 联合抗 TNF-α 药物的疗效相同。我们比较了在临床实践中进行的为期两年的开放性研究中，将皮下抗 TNF-α 药物依那西普（ETN）和阿达木单抗（ADA）与来氟米特（LEF）或甲氨蝶呤（MTX）联合使用的治疗方案的有效性和安全性。我们评估了 96 名正在接受 ADA 40mg 每两周一次或 ETN 50mg/周治疗两年的活动性类风湿关节炎患者，同时接受泼尼松龙（PDN）平均剂量 5.2±2.6mg/天。这些患者中有 54 名还接受 MTX 治疗，平均剂量为 11.7±2.6mg/周，而 42 名患者接受 LEF 治疗，剂量为每天 20mg。在 12 个月时，方差分析显示两组的 DAS28 均有改善（p<0.001），LEF 治疗组有 33.3%的患者和 MTX 治疗组有 51.8%的患者病情缓解（p=0.20）。在 18 个月时，LEF 组有 33.3%的患者病情缓解，MTX 组有 81.5%的患者病情缓解（p=0.001）。这种改善似乎与抗 TNF-α 药物无关，即使 MTX 与 ETN 联合使用时能产生最高的 DAS28 降低（p<0.078）。我们发现抗 TNF-α+MTX 和抗 TNF-α+LEF 之间在停药率或疗效指标方面没有差异。我们的数据显示，MTX 组的 DAS28 降低幅度更大，与 ETN 联合使用时，两年后的治疗效果更好。
