利那洛肽对比聚乙二醇4000治疗功能性便秘的前瞻性研究

A prospective study of linaclotide vs.macrogol 4000 in treatment of functional constipation

目的比较利那洛肽与聚乙二醇4000治疗功能性便秘(FC)的短期疗效及安全性。方法采用前瞻性、队列研究方法,门诊纳入符合标准的FC患者,根据治疗意愿分入治疗组(利那洛肽290μg·d^(-1))或对照组(聚乙二醇4000,10~20 g·d^(-1)),疗程4周。观察并比较2组患者的一般情况和基线资料,记录自发性排便(SBM)、完全自发性排便(CSBM)、Bristol粪便性状量表(BSFS)、克利夫兰便秘评分(CCS)变化,评价相关不良事件(AEs),采用单因素分析和Logistic回归分析疗效相关的影响因素。结果最终纳入统计分析的有效病例对照组79例,治疗组41例。在疗程期间,2组患者的SBM次数、CSBM次数、BSFS评分、CCS均随时间得到明显改善(P<0.05),且治疗组SBM次数、CSBM次数、CCS的改善均优于对照组(P<0.05)。第4周结束时,治疗组90%、对照组73%的患者达到疗效终点(P<0.05)。二元Logistic回归分析提示药物方案(P=0.017,OR=6.868,95%CI:1.409~33.477)和便秘治疗史(P=0.022,OR=5.332,95%CI:1.278~22.251)是临床疗效的独立影响因素。2组的AEs发生率均较低,安全性比较无显著差异(P>0.05)。结论利那洛肽对FC患者的短期疗效及安全性均较好,其疗效可能优于聚乙二醇4000,或可作为二线药物应用于对渗透性泻药反应不佳的中-重度FC患者。

AIM To compare the short-term efficacy and safety of linaclotide with macrogol 4000 in the treatment of functional constipation(FC).METHODS A prospective and cohort study was conducted in which patients with FC who met the criteria were enrolled in an out-patient clinic and selected to receive linaclotide(in the treatment group,290μg·d^(-1))or macrogol 4000(in the control group,10-20 g·d^(-1))according to treatment intention for 4 weeks.The general and baseline data of patients in both groups were observed and compared,and changes in spontaneous bowel movements(SBM),complete spontaneous bowel movement(CSBM),Bristol stool characterization scale(BSFS),and Cleveland constipation score(CCS)were recorded.Meanwhile,drug-related adverse events(AEs)were evaluated,and factors influencing efficacyrelated effects were analyzed using univariate analysis and Logistic regression.RESULTS The final effective cases included in the statistical analysis were 79 in the control group and 41 in the treatment group.During the course of treatment,the number of SBM,number of CSBM,score of BSFS,and CCS in the both groups improved significantly over time(P<0.05),and the improvement in the number of SBM,number of CSBM,and CCS in the treatment group was better than those in the control group(P<0.05).At the end of week 4,approximately 90%of patients in the treatment group and 73%in the control group reached the efficacy endpoint(P<0.05).Binary logistic regression analysis suggested that drug regimen(P=0.017,OR=6.868,95%CI:1.409 to 33.477)and history of constipation treatment drugs(P=0.022,OR=5.332,95%CI:1.278 to 22.251)were independent affecting factors of clinical outcome.The incidence of AEs was lower in the both groups,and there was no significant difference in safety comparison(P>0.05).CONCLUSION Linaclotide has favorable short-term efficacy and safety in patients with FC,and its efficacy may be better than that of macrogol 4000.Therefore,it may be used as a second-line drug in patients with moderate-to-severe FC who do not respond well to osmotic laxatives.