Rheumatology and Rehabilitation, QE Health, Auckland University, Auckland, New Zealand.
Intern Med J. 2009 Feb;39(2):95-102. doi: 10.1111/j.1445-5994.2008.01792.x.
This post-marketing study aimed to record rates of retention, adverse effects and efficacy of leflunomide in the treatment of rheumatoid arthritis (RA). The secondary objectives were to make a semi-quantitative assessment of response to treatment and to examine the effect of a loading dose on adverse events and treatment duration.
Rheumatologists in New Zealand contributed to a prospective leflunomide treatment registry. Baseline data were collected on leflunomide initiation and information about treatment experience was sought every 6 months. Each patient was followed for 2 years. Kaplan-Meier analysis was used to evaluate differences in stopping rates between lack of efficacy and adverse effects. Hazard analysis was used to evaluate the effect of using a loading dose on retention rate.
Three hundred and eight patients were enrolled in the study; complete follow-up data were available for 244 patients. Retention of patients on leflunomide was 64% at 12 months and 49.4% at 2 years. Reasons for stopping were adverse events (54 patients), loss of effect (25 patients) and miscellaneous reasons (14 patients). Use of a loading dose had no effect on retention; there was no difference in treatment duration between those who stopped from adverse effects or loss of efficacy.
Leflunomide was effective in treating RA in a group that had longer duration of disease and greater prior use of disease-modifying agents than the groups studied in clinical trials. Rates of withdrawal were lower than those reported in other post-marketing studies, but were higher than those from phase III clinical trials.
本上市后研究旨在记录来氟米特治疗类风湿关节炎（RA）的保留率、不良反应和疗效。次要目标是对治疗反应进行半定量评估，并研究负荷剂量对不良反应和治疗持续时间的影响。
新西兰的风湿病学家参与了前瞻性来氟米特治疗登记。在开始使用来氟米特时收集基线数据，并每 6 个月寻求有关治疗经验的信息。每位患者随访 2 年。Kaplan-Meier 分析用于评估因疗效不佳和不良反应而停药率的差异。风险分析用于评估使用负荷剂量对保留率的影响。
本研究共纳入 308 例患者；244 例患者可获得完整的随访数据。来氟米特治疗 12 个月时的保留率为 64%，2 年时为 49.4%。停药的原因是不良反应（54 例）、失效（25 例）和其他原因（14 例）。使用负荷剂量对保留率没有影响；因不良反应或疗效丧失而停药的患者的治疗持续时间没有差异。
来氟米特在治疗疾病持续时间较长且先前使用过改善病情的抗风湿药物的 RA 患者中有效，与临床试验中研究的患者相比。停药率低于其他上市后研究报告的水平，但高于 III 期临床试验报告的水平。
