来氟米特与甲氨蝶呤治疗银屑病关节炎皮肤病变的临床研究

A clinical study on leflunomide and methotrexate for skin involvement of psoriatic arthritis

目的评价来氟米特（LEF）、甲氨蝶呤（MTX）以及小剂量MTX和LEF联合治疗（MTX＋LEF）对银屑病关节炎（PsA）皮肤病变的疗效与安全性。方法2个中心的开放性临床对照研究。选确诊的PsA患者，接受MTX、LEF、MTX＋LEF中的任何一种治疗方案，治疗24周。以银屑病皮损面积和严重性指数（PASI）提高50％、75％（PASI 50、PASI75）为银屑病皮损疗效指标，对皮肤病变进行评估；并分析皮肤病生命质量指数（DLQI）、健康评估问卷（HAQ）的变化。计量资料的比较采用单因素方差分析、重复测量方差分析、Wilcoxon符号秩和检验，计数资料的比较采用，检验。结果治疗24周时MTX、LEF、MTX＋LEF组达到PASI 50改善的比例分别为92％、50％、94％；达到PASI 75的比例分别为75％、31％、83％。研究终点时达到PASI 50和PASI 75改善的比例在LEF组显著低于MTX和MTX＋LEF组（P〈0．05）。24周后3组HAQ得分均显著低于基线水平，联合治疗组HAQ的改善程度显著优于MTX组。MTX组和联合治疗组PASI和DLQI得分显著低于基线水平（P〈0．05）。MTX、LEF、MTX＋LEF组与药物相关的不良反应发生率分别为39％、39％、35％，无严重不良事件发生。结论3种治疗方法对PsA的皮肤病变均具有良好的疗效和安全性，小剂量MTX和LEF联合治疗PsA的皮肤病变比单用LEF具有更好的疗效。

Objective To evaluate the efficacy and safety profile of methotrexate （MTX）, leflunomide （LEF） and low-dose MTX and LEF （MTX＋LEF） combined treatment for the skin involvement of psoriatic arthritis （PsA）. Methods This was a 24 week, two-center, open-labeled, controlled trial. All subjects fulfilled the Moll and Wright criteria for definite PsA. Subjects were given one of the 3 regimens, MTX, or LEF, or MTX＋LEF. Parameters for efficacy for psoriatic rash was proportion of modified 50% and 75% improvement of psoriasis area and severity index scores （PASI）. Changes of PASI, dermatology life quality index （DLQI） and health assessment questionnaire （HAQ） were analyzed. Continuous variables were analyzed by one-way ANOVA, repeated measurement ANOVA or the Wilcoxon signed rank test. Chi-square test was used to compare dichotomous variables. Results At week 24, the percentage of patients achieving PASI 50 in MTX, LEF and MTX＋LEF group was 92% ,50% ,94% respectively, and the percentage of patients achieving PASI 75 was 75%,31.3%,83.3% respectively. At week 24, the improvement of PASI 50 and PASI 75 were better in the MTX＋LEF group and MTX group compared with LEF group （P〈0.05）. At week 24, HAQ was significantly improved compared with baseline values in MTX, LEF and MTX＋LEF group （P〈0.05）. At week 24, the improvement of HAQ was better in the MTX＋LEF group compared with MTX group. At week 24, PASI and DLQI were significantly improved in the MTX group and MTX＋LEF group compared with baseline values （P〈 0.05）. The incidence of treatment related adverse events was 39%, 39% and 35% in MTX, LEF and MTX＋ LEF group respectively. There were no serious adverse reactions. Conclusion MTX, LEF and MTX＋LEF all have good efficacy and safety profile for the skin involvement of PsA. MTX＋LEF is better for skin disorder of PsA than LEF.