来氟米特治疗日常临床应用中活动期类风湿关节炎的短期疗效和安全性：开放性、前瞻性研究。

Short-term efficacy and safety of leflunomide in the treatment of active rheumatoid arthritis in everyday clinical use : open-label, prospective study.

机构信息

René Descartes University, Institute of Rheumatology, Cochin Hospital, Paris, France.

出版信息

Clin Drug Investig. 2004;24(2):103-12. doi: 10.2165/00044011-200424020-00005.

DOI:10.2165/00044011-200424020-00005

PMID:17516696

Abstract

OBJECTIVE

To determine the efficacy and safety profile of 6-month treatment with leflunomide 20mg daily in patients with acute rheumatoid arthritis (RA) receiving treatment from 197 office-based rheumatologists in France.

METHODS

This open-label, prospective, multicentre study included 378 ambulatory RA patients who received leflunomide at a loading dose of 100mg daily on days 1-3, followed by 20mg daily for 6 months. The primary efficacy endpoint was a >/=20% response according to the American College of Rheumatology criteria (ACR 20) after 6 months. Secondary efficacy criteria were a >/=50% response (ACR 50) and a >/=70% response (ACR 70), as well as disease activity score (DAS28) responses.

RESULTS

Among the 407 selected patients, 378 patients were included in the study, all of whom were treated with leflunomide. Female patients made up 78.6% of the study population; the mean age was 57.7 +/- 12.0 years, and the mean disease duration was 9.7 +/- 8.5 years. At 6 months, the ACR 20 response rate was 48.2% (95% confidence interval [CI] 43-53%). ACR 50 and 70 response rates were 25.3% (95% CI 21.0-30.1) and 11.7% (95% CI 8.6-15.4%), respectively. According to the DAS28, 21.8% of patients had a good response, 39.9% a moderate response, and 38.2% were non-responders. The DAS28 response rate was thus 61.8% (95% CI 56.5-66.9%). Mean improvements in tender joint count were -5.6 +/- 7.4 (from baseline of 12.2 +/- 6.7), in swollen joint count were -4.2 +/- 5.7 (from baseline of 9.8 +/- 5.8), and in investigator's global assessment of RA disease activity were -20.2 +/- 25.1 (from baseline of 51.6 +/- 17.1). Treatment-related adverse events caused 15.9% of patients to discontinue the study prematurely. Serious adverse events possibly related to therapy were reported in 2.4% of patients.

CONCLUSIONS

This 6-month study carried out under daily routine practice conditions in a typical sample of RA patients showed a favourable efficacy and safety profile for leflunomide 20mg daily. The study confirms the findings of the earlier phase II and III study programme in more selected patient samples.

摘要

目的

评估来氟米特（ Leflunomide）每日 20mg 治疗 6 个月对 197 位法国门诊风湿病医生治疗的急性类风湿关节炎（RA）患者的疗效和安全性。

方法

这是一项开放标签、前瞻性、多中心研究，纳入 378 例门诊 RA 患者，前 3 天给予来氟米特 100mg 负荷剂量，之后每日 20mg，持续 6 个月。主要疗效终点是治疗 6 个月后根据美国风湿病学会（ACR）20%标准（ACR 20）的应答率≥20%。次要疗效标准是≥50%应答（ACR 50）和≥70%应答（ACR 70）以及疾病活动评分（DAS28）应答。

结果

在纳入的 407 例患者中，378 例患者被纳入研究，所有患者均接受来氟米特治疗。研究人群中女性占 78.6%；平均年龄为 57.7±12.0 岁，平均病程为 9.7±8.5 年。治疗 6 个月时，ACR 20 应答率为 48.2%（95%可信区间[CI]：43-53%）。ACR 50 和 70 应答率分别为 25.3%（95%CI：21.0-30.1）和 11.7%（95%CI：8.6-15.4%）。根据 DAS28，21.8%的患者有良好应答，39.9%的患者有中度应答，38.2%的患者无应答。因此，DAS28 应答率为 61.8%（95%CI：56.5-66.9%）。压痛关节数的平均改善为-5.6±7.4（从基线的 12.2±6.7），肿胀关节数的平均改善为-4.2±5.7（从基线的 9.8±5.8），研究者评估的 RA 疾病活动的全球评估的平均改善为-20.2±25.1（从基线的 51.6±17.1）。与治疗相关的不良事件导致 15.9%的患者提前终止研究。报告了 2.4%的患者可能与治疗相关的严重不良事件。