Litinsky Irena, Paran Daphna, Levartovsky David, Wigler Irena, Kaufman Ilana, Yaron Ilana, Yaron Michael, Caspi Dan, Elkayam Ori
Department of Rheumatology, Sourasky Medical Center, and Sackler, Faculty of Medicine, University of Tel Aviv, 6 Weizman Street, Tel Aviv 64239, Israel.
Cytokine. 2006 Jan 21;33(2):106-10. doi: 10.1016/j.cyto.2005.12.009. Epub 2006 Feb 17.
The purpose of this open pilot study was to assess possible mechanisms of the effects of leflunomide by studying the influence of the drug on the serum levels of MMP-1, MMP-3, IL-10, IL-6 and their possible correlation with clinical disease parameters.
Thirty patients with long standing active rheumatoid arthritis were enrolled in this study. All patients failed at least 5 DMARDs in the past and were on stable treatment for at least 3 months before starting the protocol. The patients received a loading dose of 100 mg for 3 days followed by 20 mg/day thereafter and followed up monthly for 6 months. Disease activity was assessed at baseline, 2 weeks, and every month of therapy thereafter using the following variables: tender joint count, swollen joint count, morning stiffness duration, pain, tiredness, physician's and patient's global assessment, using VAS, ESR and CRP. Clinical effects of the treatment regimen were calculated using the American College of Rheumatology (ACR) criteria for clinical response. Adverse events were recorded. Serum levels of MMP-1, MMP-3, IL-10 and IL-6 were measured before and 3 months after starting the protocol.
Except for tiredness, a statistically significant improvement in all clinical and laboratory parameters of disease activity was reached after 3 months. At this time point the ACR-20 response rate was 46.2%. The levels of MMP-1, MMP-3, IL-6 and IL-10 decreased significantly after 3 months. A statistically significant correlation between serum levels of MMP-1, IL-10 and IL-6 and clinical and laboratory parameters was also shown. After 6 months, 16 out of 30 patients withdrew from the study [adverse events (35.4%), lack of efficacy (9.7%), and low compliance (6.4%)].
Leflunomide was clinically efficacious in this group of long standing resistant RA in an open study "real life" design. These results comply with those reported in previous clinical trials. Serum MMP-1, MMP-3, IL-10 and IL-6 levels decreased significantly. Despite high withdrawal rate, no serious adverse effects were recorded.
这项开放性初步研究的目的是通过研究来氟米特对血清基质金属蛋白酶-1（MMP-1）、基质金属蛋白酶-3（MMP-3）、白细胞介素-10（IL-10）、白细胞介素-6（IL-6）水平的影响及其与临床疾病参数的可能相关性，评估来氟米特作用的可能机制。
30例长期活动性类风湿关节炎患者纳入本研究。所有患者过去至少5种改善病情抗风湿药（DMARDs）治疗失败，且在开始本方案前已接受稳定治疗至少3个月。患者先接受3天100mg的负荷剂量，之后20mg/天，每月随访6个月。在基线、2周及此后治疗的每个月，使用以下变量评估疾病活动度：压痛关节数、肿胀关节数、晨僵持续时间、疼痛、疲劳、医生和患者整体评估（采用视觉模拟评分法）、红细胞沉降率（ESR）和C反应蛋白（CRP）。根据美国风湿病学会（ACR）临床反应标准计算治疗方案的临床疗效。记录不良事件。在开始方案前及开始后3个月测量血清MMP-1、MMP-3、IL-10和IL-6水平。
3个月后，除疲劳外，疾病活动度的所有临床和实验室参数均有统计学意义的改善。此时ACR-20反应率为46.2%。3个月后，MMP-1、MMP-3、IL-6和IL-10水平显著下降。血清MMP-1、IL-10和IL-6水平与临床和实验室参数之间也显示出统计学意义的相关性。6个月后，30例患者中有16例退出研究[不良事件（35.4%）、缺乏疗效（9.7%）和依从性差（6.4%）]。
在一项开放性研究“真实生活”设计中，来氟米特对这组长期耐药的类风湿关节炎患者临床有效。这些结果与先前临床试验报道的结果一致。血清MMP-1、MMP-3、IL-10和IL-6水平显著下降。尽管退出率高，但未记录到严重不良反应。
