Weinblatt M E, Kremer J M, Coblyn J S, Maier A L, Helfgott S M, Morrell M, Byrne V M, Kaymakcian M V, Strand V
Brigham and Women's Hospital, Boston, Massachusetts 02115, USA.
Arthritis Rheum. 1999 Jul;42(7):1322-8. doi: 10.1002/1529-0131(199907)42:7<1322::AID-ANR4>3.0.CO;2-P.
To examine the safety and pharmacokinetics of and clinical response to leflunomide, a de novo pyrimidine synthesis inhibitor, when administered to patients with active rheumatoid arthritis (RA) who have been receiving long-term methotrexate therapy.
This was an open-label, 52-week study in which 30 patients with RA that remained active despite therapy with methotrexate at 17+/-4 mg/week (mean +/- SD) for > or =6 months were given leflunomide, 10-20 mg/day. Patients were assessed for adverse effects, pharmacokinetic measurements of leflunomide and methotrexate, and clinical response by American College of Rheumatology (ACR) 20% response criteria.
Twenty-three patients completed 1 year of treatment. No significant pharmacokinetic interactions between leflunomide and methotrexate were noted. This combination therapy was generally well tolerated clinically, with the exception of elevations of liver enzyme levels. Seven patients withdrew from the treatment regimen: 2 withdrawals were voluntary, 3 were due to persistent elevation of plasma transaminase levels, and 2 were due to lack of efficacy. Of the patients, 16 (53%) met ACR 20% response criteria. Two met ACR criteria for remission after 1 year.
The combination of methotrexate and leflunomide has therapeutic potential in RA.
研究新型嘧啶合成抑制剂来氟米特用于长期接受甲氨蝶呤治疗的活动性类风湿关节炎（RA）患者时的安全性、药代动力学及临床反应。
这是一项为期52周的开放标签研究，30例尽管以17±4mg/周（均值±标准差）的甲氨蝶呤治疗≥6个月但病情仍活动的RA患者，给予来氟米特10 - 20mg/天。评估患者的不良反应、来氟米特和甲氨蝶呤的药代动力学指标，以及采用美国风湿病学会（ACR）20%反应标准评估临床反应。
23例患者完成了1年治疗。未发现来氟米特和甲氨蝶呤之间存在显著的药代动力学相互作用。除肝酶水平升高外，该联合治疗在临床上总体耐受性良好。7例患者退出治疗方案：2例为自愿退出，3例因血浆转氨酶水平持续升高，2例因缺乏疗效。16例（53%）患者达到ACR 20%反应标准。2例在1年后达到ACR缓解标准。
甲氨蝶呤和来氟米特联合用药在RA治疗中具有潜在疗效。
