两种地塞米松棕榈酸酯注射液治疗类风湿关节炎的多中心随机双盲对照观察

A multicenter, randomized, double-blind, controlled study on the injection of two kinds of dexame- thasone palmitate in the treatment of rheumatoid arthritis

目的依据药品临床试验管理规范（GCP）观察评价国产与进口地塞米松棕榈酸酯注射液治疗类风湿关节炎（RA）膝关节受累是否具有相同的临床疗效及安全性。方法采用多中心、双盲、随机、平行对照研究，237例有膝关节轻、中度肿胀的RA患者入组观察，随机分为治疗组（国产）118例和对照组（进口）119例，分别应用2种地塞米松棕榈酸酯注射液8mg关节腔注射1次，1周后回访。主要疗效指标为进行关节腔药物注射的膝关节上、下缘周径，次要疗效指标包括关节压痛指数和受试者自我评价，并对不良事件进行统计记录。采用协方差分析、t检验或Wilcoxon秩和检验、，检验或Fisher精确概率法进行统计分析。结果治疗组与对照组治疗后上缘周径分别为（37．2±3．3）cm和（36．4±3．9）cm，下缘周径分别为（34．4＋2．9）cm和（33．9±3．4）cm，比治疗前的上缘周径[（38．1±3。3）cm和（37．3±4．0）cm]，以及下缘周径[（35．1±3．0）cm和（34．6±3．6）cm]明显缩小（P〈0．01）。治疗后2组关节压痛指数也有显著改善（P〈0．01）。治疗组和对照组在受试者自我评价方面为很大好转和好转的比例分别是67．5％（79／117）和74．8％（86／115）。全部主要和次要疗效指标之间差异无统计学意义（Jp〉0．05）。试验过程中相关不良事件发生率在治疗组和对照组分别为6．8％（8／118）和4．2％（5／119），差异无统计学意义（P〉0．05）。结论国产地塞米松棕榈酸酯注射液与进口同类产品在治疗RA上具有相同的临床疗效及安全性。接受注射的膝关节上、下缘周径可能成为用于评估关节炎局部注射治疗效果的参考指标之一。

Objective To evaluate the efficacy and safety of two forms of preparations of dexame- thasone palmitate in the treatment of rheumatoid arthritis （RA）. Methods A muhicenter, double-blind, ran- domized, parallel-group clinical trial was carried out according to good clinical practice （GCP）. A total of 237 cases of RA patients with mild to moderate knee swelling were randomly divided into the treatment group （n= 118 ） or the control group （n=119） and were treated with two kinds of dexamethasone palmitate 8 mg injection respectively. The primary efficacy endpoints were the circumference of the knee joint at the upper and the lower edge after the intra-articular injection. The secondary efficacy endpoints were joint tenderness index and patients general assessment. The adverse events were recorded. Analysis of covariance, t test or Wilcoxon test, X2 test or Fisher exact test were used for statistical analysis. Results The upper edges of the treatment group and the control group after treatment were （37.2±3.3） cm and （36.4±3.9） cm respectively, and the lower edges of the two groups were （34.4±2.9） cm and （33.9±3.4） cm respectively. They were all significantly smaller than the edges before treatment [ （ 38.1 ± 3.3 ） cm and （ 37.3±4.0 ） cm of the upper edges, （ 35.1 ±3.0） cm and （34.6±3.6） cm of the lower edges respectively） （P〈0.01）]. After treatment, the joint tenderness index were improved （P〈0.01）. A total ratio of great improvement and improvement of patients general assessment of the two group patients were 67.5% （79/117） and 74.8% （86/115） respectively. No statistical significant difference was found in all primary and secondary efficacy endpoints between the two groups （P〉0.05）. During the clinical trial, the incidence of adverse events related to the treatment of two groups were 4.2% and 6.8%, without any significant difference （P〉0.05）. Conclusion New preparation of dexamethasone palmitate has the same efficacy and safety as the imported producted in the treatment of RA. The circumference of the knee joints at the upper and the lower edge may be used to assess the effects of intra-articular injections.