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

【摘要】 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χ2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 < 0.012 7）；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 < 0.012 7）。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。

Efficacy of tazarotene 0.05%/betamethasone dipropionate 0.05% cream in the treatment of mild to moderate psoriasis vulgaris: a multicenter clinical observational study

【Abstract】 Objective To preliminarily evaluate clinical efficacy and safety of tazarotene 0.05%/betamethasone dipropionate 0.05% cream in the treatment of psoriasis vulgaris. Methods A multicenter, randomized, double-blinded, single-dummy, parallel-controlled clinical trial was conducted. Subjects with mild to moderate psoriasis vulgaris were randomized into 4 groups at a ratio of 2∶1∶1∶1, including tazarotene 0.05%/betamethasone dipropionate 0.05% cream （Taz/Bp） group, betamethasone dipropionate 0.05% cream （Bp） group, tazarotene 0.05% gel （Taz） group and cream vehicle control （Plb） group. The treatment lasted 4 weeks. After 1, 2 and 4 weeks of treatment, efficacy and safety of drugs were evaluated in the above groups. Two-way analysis of variance model with main effects was used to compare continuous indices, least significant difference t-test was used for multiple comparisons, and chi-square test or Fisher′s exact test for comparisons of categorical data. Results A total of 300 subjects were enrolled from 7 research centers, including 120 in the Taz/Bp group, 60 in the Bp group, 60 in the Taz group and 60 in the Plb group. After 4 weeks of treatment, proportions of patients achieving a 75% reduction in PASI （PASI75） were 35.83%, 20.00%, 18.33% and 6.67% in the Taz/Bp, Bp, Taz and Plb groups respectively, and there was a significant difference among the 4 groups （P < 0.05）; the proportion of patients achieving PASI75 was significantly higher in the Taz/Bp group than in the Plb group （α = 0.05, P < 0.05） and Taz group （α = 0.025, P < 0.025）, but there was no significant difference between the Taz/Bp group and Bp group （α = 0.016 7, P > 0.016 7）; the proportions of patients achieving PASI90 were 25.00%, 8.33%, 5.00% and 1.67% in the Taz/Bp, Bp, Taz and Plb groups respectively, which significantly differed among the 4 groups （P < 0.05）, and the Taz/Bp group showed a significantly increased proportion of patients achieving PASI90 compared with the Plb group （P < 0.05）, Taz group （P < 0.025）and Bp group （P < 0.016 7）. All the tested drugs were well tolerated in the 4 groups. Adverse drug reactions occurred in 15 （12.50%）, 5 （8.33%）, 19 （31.67%）and 9 （15.00%） patients in the Taz/Bp, Bp, Taz and Plb groups respectively. The incidence rate of adverse drug reactions significantly differed among the 4 groups （P = 0.004）, and was significantly lower in the Taz/Bp group than in the Taz group （P < 0.05）, but insignificantly different between the Taz/Bp group and Bp or Plb group （both P > 0.05）. Conclusion Tazarotene 0.05%/betamethasone dipropionate 0.05% cream is effective and safe for the treatment of psoriasis vulgaris.