美沙拉秦缓释片治疗活动期溃疡性结肠炎的多中心、单盲、随机对照研究

Mesalazine modified-release tablets in the treatment of ulcerative colitis in active phase： a multi-center, single-blinded and randomized controlled study

目的 评价美沙拉秦缓释片治疗轻度和中度活动期UC患者的有效性和安全性.方法 采用多中心、单盲、随机对照设计,纳入2010年11月至2012年1月18所医院的251例活动期UC患者,分成美沙拉秦缓释片组123例和美沙拉秦肠溶片组128例,每日3次,每次分别口服美沙拉秦缓释片和美沙拉秦肠溶片800 mg,疗程为8周.计算最终评估时UC疾病活动指数（UC-DAD差值,即入选时UC-DAI-最终评估时UC-DAI,以此为主要疗效指标.次要疗效指标为缓解率和有效率.计算两组的不良反应发生率并以此为安全性指标.若美沙拉秦缓释片组与美沙拉秦肠溶片组最终评估时UC-DAI差值的差值的95％可信区间下限＞-1.0,即可认为美沙拉秦缓释片不劣于美沙拉秦肠溶片的假设成立.主要疗效指标及亚组分析在调整后进行协方差模型分析.次要疗效指标及不良反应发生率的比较采用卡方检验.结果 美沙拉秦缓释片组最终评估时UC-DAI差值为2.84,美沙拉秦肠溶片组为2.56,两组间差值为0.27,两组间最终评估时UC-DAI差值的差值的95％可信区间下限为-0.34,美沙拉秦缓释片不劣于美沙拉秦肠溶片的假设成立.美沙拉秦缓释片组和美沙拉秦肠溶片组的缓解率分别为48.33％（58/120）和55.65％（69/124）,有效率分别为63.33％（76/120）和66.94％ （83/124）,组间比较差异均无统计学意义（P均＞0.05）.在美沙拉秦缓释片组和美沙拉秦肠溶片组中,轻度UC患者（入选时UC-DAI为3∽5分）的最终评估时UC DAI差值分别为2.16和2.05,两组间差值为0.11;中度UC患者（入选时UC-DAI为6∽8分）则分别为3.49和3.03,两组间差值为0.46,组间比较差异均无统计学意义（P均＞0.05）.美沙拉秦缓释片组和美沙拉秦肠溶片组的不良反应发生率分别为6.61％（8/121）和10.24％（13/127）,差异无统计学意义（P＞0.05）.两组均未发生严重不良反应.结论 应用美沙拉秦缓释片治疗轻度和中度活动期UC患者疗效好且安全性高.

Objective To evaluate the efficacy and safety of mesalazine modified-release tablets in the treatment of mild and moderate active ulcerative colitis （UC）.Methods This study was a multicenter,single-blinded and randomized controlled study.A total of 251 active UC patients in 18 hospitals were enrolled into this study from November 2010 to January 2012.The subjects were divided into the mesalazine modified-release tablets group （n=123） and the mesalazine enteric-coated tablets group （n=128）,three times daily,each of which took mesalazine modified-release tablets or mesalazine enteric coated tablets 800 mg,respectively,and the course of treatment was eight weeks.The difference of UC disease activity index （UC-DAI）,UC-DAI at the beginning minus UC-DAI at the final evaluation,was calculated at final evaluation.And this was the primary efficacy parameter.Complete remission rate and effective rate were considered as the secondary efficacy parameter.Adverse drug reactions rates of two groups were calculated and taken as safety evalution.If the lower limit of the 95 % confidence interval was more than-0.1 in the difference of the decrease in UC-DAI between the two groups,the non-inferiority of mesalazine modified release tablets to mesalazine enteric-coated tablets was demonstrated.The analysis of covariance model was used for the primary efficacy parameter and the sub-group analysis.And chisquare test was used for the comparison between the two groups in the secondary efficacy parameter and in the adverse drug reactions.Results At the final evaluation,the decrease in UC-DAI of mesalazine modified-release tablets group was 2.84 and that of mesalazine enteric-coated tablets group was 2.56.The reduction degree was 0.27.The lower limit of the 95 % confidence interval in the difference of the decrease in UC DAI between the two groups was-0.34,which demonstrated the non-inferiority of mesalazine modified release tablets to mesalazine enteric-coated tablets.The complete remission rates of mesalazine modified release tablets group and mesalazine enteric-coated tablets group were 48.33% （58/120） and 55.65% （69/124） and the effective rates were 63.33% （76/120） and 66.94% （83/124）,and there was no statistically significant difference between the two groups （all P〉 0.05）.At final evaluation,the decrease in UC DAI of mild patients （UC DAI 3 to 5 at enrollment） of mesalazine modified-release tablets group and mesalazine enteric-coated tablets group were 2.16 and 2.05,respectively; the difference of mesalazine modified release tablets group and mesalazine enteric coated tablets group of reduction degree of UC-DAI was 0.11,that of moderate patients （UC-DAI 6 to 8 at enrollment） were 3.49 and 3.03,respectively,the difference of mesalazine modified-release tablets group and mesalazine enteric-coated tablets group of reduction degree of UC DAI was 0.46,and there was no statistically significant difference between the groups （all P〉0.05）.The adverse drug reactions rates of mesalazine modified-release tablets group and mesalazine enteric coated tablets group were 6.61% （8/121） and 10.24% （13/127）,and there was no statistically significant difference between the two groups （P〉 0.05）.No serious adverse drug reactions were found in two groups.Conclusion Mesalazine modified release tablets has good efficacy and high safety in the treatment of mild to moderate active UC.