不同浓度配比的他扎罗汀倍他米松乳膏治疗寻常型银屑病的疗效观察

Efficacy of tazarotene/betamethasone dipropionate cream at different concentration ratios in the treatment of psoriasis vulgaris:a clinical observation

目的探索不同浓度配比的他扎罗汀倍他米松乳膏治疗寻常型银屑病的疗效和安全性,筛选人体使用的最佳药物配比浓度。方法采用多中心、随机、双盲、多剂量对照研究设计,2008年12月至2009年4月,中国医学科学院皮肤病医院等7个研究中心共纳入180例寻常型银屑病患者,按1∶1∶1∶1∶1比例随机分配进入4个试验组(他扎罗汀/二丙酸倍他米松浓度配比分别为0.025%/0.025%、0.05%/0.025%、0.025%/0.05%、0.05%/0.05%,简称为试验1、2、3和4组)和对照组(基质),每日用药1次,持续4周。用药后第1、2、4周分别评价各组药物的疗效和安全性。多组计量资料比较采用方差分析和LSD-t检验,多组分类资料的比较用χ^2检验或Fisher精确概率检验,采用CMH法分析各组的银屑病皮损面积和严重程度指数(PASI)反应率数据。结果用药4周,试验1、2、3、4组和对照组改善达PASI75的患者分别为11例(30.56%)、12例(33.33%)、12例(33.33%)、19例(52.78%)和2例(5.56%),各试验组达PASI75的患者比例均显著高于对照组(均P<0.0127);此外,试验药物1、2、4组达PASI90的患者比例亦显著高于对照组(均P<0.0127)。用药4周,试验1、2、3、4组PASI评分下降率分别达59.52%±26.79%、57.19%±31.98%、56.85%±30.46%和68.21%±37.20%,均显著高于对照组(20.07%±28.55%)(LSD-t=5.36、5.05、5.00、6.55,均P<0.001)。试验4组的综合疗效表现更突出。试验1、2、3、4组和对照组药物耐受性良好,分别发生不良反应11例(30.56%)、8例(22.22%)、2例(5.56%)、4例(11.11%)和2例(5.56%),试验1组不良反应发生率显著高于对照组(P=0.012),试验2、3、4组与对照组比较差异无统计学意义(均P>0.05)。结论0.05%/0.05%他扎罗汀倍他米松乳膏可作为后继治疗寻常型银屑病临床研究的推荐配比浓度。

Objective To evaluate the efficacy and safety of tazarotene/betamethasone dipropionate cream at different concentration ratios in the treatment of psoriasis vulgaris,and to determine the optimal drug concentration ratio for clinical use.Methods A multicenter,randomized,double-blinded,multi-dose controlled study was conducted.From December 2008 to April 2009,a total of 180 patients with psoriasis vulgaris were enrolled from 7 research centers,such as Hospital for Skin Diseases,Chinese Academy of Medical Sciences and Peking Union Medical College.These patients were randomly and equally divided into 5 groups:treatment groups 1,2,3,4 treated with tazarotene/betamethasone dipropionate cream at concentration ratios of 0.025%/0.025%,0.05%/0.025%,0.025%/0.05%and 0.05%/0.05%respectively once a day,and control group treated with the cream vehicle once a day.The treatment lasted 4 weeks.Efficacy and safety were evaluated after 1,2 and 4 weeks of treatment.One-way analysis of variance and least significant difference(LSD)-t test were used to compare measurement data among several groups,chi-square test and Fisher′s exact test to compare categorical data among groups,and Cochran-Mantel-Haenszel(CMH)test to compare psoriasis area severity index(PASI)response rates between groups.Results After 4 weeks of treatment,11 patients(30.56%),12(33.33%),12(33.33%),19(52.78%)and 2(5.56%)in the treatment groups 1,2,3,4 and control group respectively achieved a 75%reduction in PASI(PASI75),and the proportions of patients achieving PASI75 were significantly higher in the treatment groups than in the control group(all P<0.0127).Additionally,the proportions of patients achieving PASI90 were also significantly higher in the treatment groups 1,2 and 4 than in the control group(all P<0.0127).After 4 weeks of treatment,the rates of reduction in PASI scores were 59.52%±26.79%,57.19%±31.98%,56.85%±30.46%and 68.21%±37.20%in treatment groups 1,2,3,and 4 respectively,which were all significantly higher than the rate of reduction in the control group(20.07%±28.55%;LSD-t=5.36,5.05,5.00,6.55,all P<0.001).The treatment group 4 showed marked comprehensive efficacy.All the tested drugs were well tolerated in the patients,and adverse reactions occurred in 11(30.56%),8(22.22%),2(5.56%),4(11.11%)and 2(5.56%)cases in the treatment groups 1,2,3,4 and control group respectively.The incidence rate of adverse reactions was significantly higher in the treatment group 1 than in the control group(P=0.012),and there was no significant difference among the treatment groups 2,3,4 and control group(all P>0.05).Conclusion The tazarotene 0.05%/betamethasone dipropionate 0.05%cream can be recommended for subsequent clinical trials in psoriasis vulgaris.