摘要 越来越多的证据显示，类风湿关节炎需早期持续使用病情改善抗风湿药（DMARD）治疗。来氟米特是1998年批准治疗类风湿的DMARD，上市后监测、病例报道和观察研究主要强调了某些少见或未预料到的副作用，因此，在其广泛应用10年后进行效益/风险比评估是合适的。我们通过广泛检索有关资料和文献来进行评估。双盲安慰剂对照试验及随后4年的开放观察研究均显示，来氟米特治疗类风湿有效，仅有1项研究显示其使用24个月时的疗效与甲氨蝶呤相似，但优于柳氮磺吡啶。然而，临床耐受性研究显示，与甲氨蝶呤和安慰剂相比，因其毒性作用和缺乏疗效而撤药率较高。副作用包括胃肠道不适、高血压、头疼、肝毒性和脱发，及容易感染和外周神经炎。胃肠道反应与柳氮磺吡啶相似，但比甲氨蝶呤高，严重的药物诱导性肝毒性致住院者罕见（0.02%），但也有因肝衰竭致命的个别报道。虽然未最后证实，来氟米特引起体重降低和肺纤维化的机率似乎增高。随机安慰剂对照试验发现，来氟米特联合甲氨蝶呤或柳氮磺吡啶有效，但需更多的研究来证实它与其他DMARD药（尤其是生物制剂）联合的疗效。动物研究显示，来氟米特的活性代谢产物有致畸性，因此育龄期男性和女性均需避孕。患者疗效和副作用不同可能与遗传、药代动力学和生物化学因素有关。使用过程中，应进行血液和血压监测，临床无效者应行治疗药物监测。总之，来氟米特与柳氮磺吡啶和甲氨蝶呤相似，是有效的DMARD，临床有效，并改善放射学，但副作用需多监测。对于生育期成人及以前有肺病和肝病患者来说，使用要谨慎。

附原文： Abstract Evidence is accumulating for the early sustained usage of disease-modifying anti-rheumatic drugs (DMARDs) in rheumatoid arthritis. Leflunomide was licensed for the treatment of rheumatoid arthritis in 1998. Postmarketing surveillance, case reports and observational studies have highlighted less common or unexpected adverse events. Therefore, it is appropriate that we review the benefit-risk profile of leflunomide after 10 years of widespread usage. A wide-based search of relevant literature was performed to formulate this assessment. The improvements in rheumatoid arthritis shown by double-blind, randomized controlled trials (RCTs) of leflunomide have now been shown to be maintained beyond 4 years in open-label extension studies. Leflunomide is comparable to methotrexate, but better than sulfasalazine at 24 months in only one study. However, tolerance in clinical practice research shows higher than expected withdrawal rates due to both toxicity and lack of efficacy when compared with methotrexate and placebo. Adverse events reported include gastrointestinal upset, hypertension, headache, hepatotoxicity and hair loss, as well as predisposition to infection and peripheral neuropathy. The incidence of gastrointestinal adverse effects for leflunomide is similar to sulfasalazine but higher than those seen with methotrexate. Serious drug-induced hepatotoxicity leading to hospitalization is rare (0.02%), but isolated fatalities from liver failure have been documented. It is considered likely, but not yet proven, that there may be an increased incidence of weight loss and interstitial lung disease with leflunomide. Leflunomide in combination with methotrexate or sulfasalazine is an effective regimen in RCTs utilizing placebo controls, but more research is needed to confirm its effectiveness in combination with other DMARDs, particularly biologicals. The active metabolite of leflunomide is teratogenic in animal studies and is also found in breast milk. Therefore, contraception is advised in both males and females of child-bearing potential. There are genetic, pharmacokinetic and biochemical reasons to explain variation in both patient response and adverse event profile. Hence, blood and blood pressure monitoring are recommended and therapeutic drug monitoring should be considered in clinical nonresponders. Leflunomide is an effective DMARD that sustains a clinical and radiological response comparable to sulfasalazine and methotrexate. However, adverse effects necessitate frequent monitoring. It should be used with caution in those of child-bearing potential and with pre-existing lung and liver disease.

摘自：Alcorn N, Saunders S，Madhok R. Benefit-risk assessment of leflunomide: an appraisal of leflunomide in rheumatoid arthritis 10 years after licensing. Drug Saf. 2009;32(12):1123-34