不同临床药物治疗腹泻型肠易激综合征有效性和安全性的网状Meta分析

Network Meta-analysis of efficacy and safety of different drugs used in diarrhea-predominant irritable bowel syndrome

目的通过网状Meta分析系统评估腹泻型肠易激综合征(IBS-D)临床常用治疗药物的有效性和安全性,为临床治疗IBS-D的药物选择提供更可靠的参照。方法系统检索了PubMed、Embase、Cochrane Library、中国知网(CNKI)、万方、中国生物医学文献数据库(CBM),搜索8种临床常用药物(阿洛司琼、雷莫司琼、伊卢多啉、奥替溴铵、美沙拉嗪、阿米替林、蒙脱石散、乳酸菌)治疗IBS-D的随机对照试验,检索时限为从建库至2022年10月,无检索语言限制。2名研究者根据纳入和排除标准分别独立进行文献筛选、质量评估和数据提取,使用Stata15.0软件和R3.4.0软件进行统计分析。结果最终纳入20个随机对照研究。从治疗的有效性和安全性角度看,阿米替林对IBS-D的治疗效果最好,累积排序曲线下面积(SUCRA)为0.8362367;其次为阿洛司琼(500μg,q.d.),SUCRA为0.7320461;有效性最差的为伊卢多啉(5 mg,b.i.d),SUCRA为0.1821453。和安慰剂相比,阿洛司琼(1 mg,b.i.d.)[OR=2.7,95%CI=(1.2,6.1)]和阿米替林[OR=4.0,95%CI=(1.2,14.0)]能够显著改善IBS-D患者的整体症状。雷莫司琼和伊卢多啉的有效性有剂量依赖性,每日使用剂量越高,有效性越好。阿米替林对IBS-D的不良反应最少,SUCRA为0.8823442;其次为雷莫司琼(1μg,q.d.),SUCRA为0.8384067;不良反应最多的药物是阿洛司琼(1 mg,b.i.d.),SUCRA为0.1125367。结论当前证据显示,阿米替林对于IBS-D的治疗效果优于其他药物,且不良反应最小。受纳入各个研究数量和质量的限制,该结论尚需更多质量高、样本量大的研究加以验证。

Objective To evaluate the efficacy and safety of commonly used drugs in clinical treatment of diarrhea-predominant irritable bowel syndrome(IBS-D)by network Meta-analysis,aiming to provide a more reliable reference for drug selection in clinical treatment of IBS-D.Methods PubMed,Embase,Cochrane Library,CNKI,WanFang,and China Biomedical Database(CBM)databases were systematically searched for randomized controlled trials of 8 clinically used drugs(alosetron,ramosetron,eluxadoline,otilonium bromide,mesalazine,amitriptyline,montelukast,and lactobacillus)for the treatment of IBS-D.The time limit was from database construction to October 2022,and there was no language limitation.2 researchers independently conducted literature screening,quality assessment and data extraction according to inclusion and exclusion criteria.Stata15.0 and R3.4.0 software was used for statistical analysis.Results 20 randomized controlled studies were eventually included.In terms of efficacy and safety of treatment,amitriptyline was the most effective for IBS-D with a surface under the cumulative ranking area(SUCRA)of 0.8362367;followed by alosetron(500μg,q.d.)with a SUCRA of 0.7320461;and the least effective was eluxadoline(5 mg,b.i.d.)with a SUCRA of 0.1821453.Compared with placebo,alosetron(1 mg,b.i.d.)[OR=2.7,95%CI=(1.2,6.1)]and amitriptyline[OR=4.0,95%CI=(1.2,14.0)]can significantly improve the overall symptoms of patients with IBS-D.The efficacy of ramosetron and eluxadoline was dose-dependent,and the higher the daily dose,the better the efficacy.Amitriptyline had the least adverse reactions on IBS-D with a SUCRA of 0.8823442,followed by ramosetron(1μg,q.d.)with a SUCRA of 0.8384067,and the drug with the most adverse reactions was alosetron(1 mg,b.i.d.)with a SUCRA of 0.1125367.Conclusion Current evidence suggests that amitriptyline is superior to other drugs in the treatment of IBS-D with minimal adverse reactions.Limited by the quantity and quality of the included studies,this conclusion needs to be verified by more high-quality and large sample size studies.