基于meta分析评估TNF拮抗剂对IBD术后并发症的影响及其预防术后复发的作用

发布时间：2018-04-07 15:50

本文选题：英夫利希单抗　切入点：TNF拮抗剂　出处：《第四军医大学》2014年博士论文

【摘要】：【背景】炎症性肠病（inflammatory bowel disease，IBD）主要包括溃疡性结肠炎（ulcerativecolitis，UC）和克罗恩病（Crohn’s disease，CD）。虽然以肿瘤坏死因子（tumor necrosisfactor，TNF）拮抗剂为代表的生物制剂在IBD的治疗中取得重要进展，IBD患者仍然在其患病过程中不得不面临手术。随着TNF拮抗剂在临床中的大量使用，其围手术期的安全性成为临床医生关注的焦点。本课题运用meta分析方法，全面梳理和荟萃现有临床证据，系统评价TNF拮抗剂对IBD术后并发症的影响及其预防术后复发的作用。【目的】 1．评估UC患者中术前英夫利希单抗的治疗对腹部手术早期预后的临床安全性和有效性。 2．评估接受腹部手术的CD患者中术前英夫利希单抗的使用对早期术后并发症的影响。 3．通过网络meta分析方法比较5-氨基水杨酸、免疫抑制剂和生物制剂预防CD术后复发的疗效。【方法】 1．通过搜索PubMed和Embase数据库筛选比较术前接受或没有接受英夫利希单抗的UC患者术后并发症的观察性对照研究。主要观察终点为总体并发症发生率。次要观察终点包括感染性和非感染性并发症。我们计算合并比值比（odds ratio，OR）和95%可信区间（confidence interval，CI）作为荟萃变量。 2．通过搜索PubMed和Embase数据库筛选比较术前接受或没有接受英夫利希单抗的CD患者术后并发症的对照研究。使用随机效应模型的meta分析计算合并比值比和95%可信区间，荟萃变量包括总体并发症发生率以及主要、次要、感染性和非感染性并发症。 3．通过搜索PubMed、Embase和Cochrane图书馆等数据库（截止2013年11月）来筛选以安慰剂作对照或者两两比较5-氨基水杨酸、免疫抑制剂和生物制剂三类药物预防CD术后复发的随机试验。主要观察终点为预防内镜复发的疗效，次要观察终点包括临床复发和不良事件。运用混合效应比较模型实施贝叶斯网络meta分析，以同时合并直接和间接证据。【结果】 1．13项研究合计2933名UC患者纳入本项meta分析。术前英夫利希单抗治疗与总体（OR=1.09；95%CI0.87-1.37；P=0.47）、感染性（OR=1.10；95%CI0.51-2.38；P=0.81）和非感染性（OR=1.10；95%CI0.76-1.59；P=0.61）术后并发症之间均无显著相关性。术前12周内使用英夫利希单抗可能是抗感染的保护性因素（OR=0.43；95%CI0.22-0.83；P=0.01）。没有发现发表偏倚。 2．18项研究合计5769名CD患者纳入本项meta分析。术前英夫利希单抗治疗与总体（OR=1.45；95%CI1.04-2.02；13项研究，2538人）、感染性（OR=1.47；95%CI1.08-1.99；10项研究，2116人）和非感染性（OR=2.29；95%CI1.14-4.61；3项研究，729人）术后并发症均有显著相关性。英夫利希单抗和对照组之间在主要（OR=1.39；95%CI0.85-2.27；9项研究，3696人）和次要（OR=1.39；95%CI0.57-3.40；5项研究，753人）并发症发生率上并无显著性差异。没有发现发表偏倚。 3．15项试验合计1507名CD患者纳入本项网络meta分析。生物制剂较安慰剂、5-氨基水杨酸或免疫抑制剂能更大幅度更显著地减少内镜和临床复发。免疫抑制剂较5-氨基水杨酸或安慰剂能更有效地预防内镜和临床复发，但有更高的不良事件发生率。5-氨基水杨酸比安慰剂更更有效地预防临床复发，且不增加不良反应发生率。【结论】术前英夫利希单抗的使用不会影响UC患者的早期术后并发症，但会轻微增加CD患者的术后并发症，，且主要是术后感染。5-氨基水杨酸、免疫抑制剂和生物制剂都能有效预防CD术后复发。生物制剂是三者中最有效的药物。
[Abstract]:Background background

Inflammatory bowel disease ( IBD ) mainly includes ulcerative colitis ( UC ) and Crohn ' s disease ( CD ) . Although the biological agent represented by tumor necrosis factor ( TNF ) antagonist has made important progress in the treatment of IBD , patients with IBD still have to face surgery in the course of its illness . With the large use of TNF antagonists in clinical practice , the safety of perioperative period has become the focus of the clinician ' s attention .

Purpose of the project

1 . To assess the clinical safety and efficacy of pre - operative infliximab in patients with UC for the early prognosis of abdominal surgery .

2 . To assess the effect of the use of pre - operative infliximab in CD patients undergoing abdominal surgery on early postoperative complications .

3 . The curative effect of 5 - aminosalicylic acid , immunosuppressive agent and biological agent on the prevention of postoperative recurrence of CD was compared by means of network meta - analysis .

Methodology

1 . A comparative study of postoperative complications of patients with UC who received or did not receive infliximab after surgery was screened by search of the literature and Embase database . The primary observation endpoint was the overall complication rate . Secondary observation endpoints included infectious and non - infectious complications . We calculated the odds ratio ( OR ) and 95 % confidence interval ( CI ) as meta - variables .

2 . A comparative study of post - operative complications of CD patients who received or did not receive infliximab after surgery was screened by the search of the literature and Embase database . The pooled odds ratio and 95 % confidence interval were calculated using the meta - analysis of the random effect model , which included the overall complication rate and the primary , secondary , infectious and non - infective complications .

3 . A randomized trial for the prevention of postoperative recurrence of CD post - operation was screened by searching for databases ( as of November 2013 ) in the literature , Embase , and Central Library ( as of November 2013 ) . The primary observation endpoints were the efficacy of prevention of relapse , secondary observation endpoints included clinical relapse and adverse events . Using a mixed - effect comparison model , a meta - analysis of Bayesian network was conducted to combine direct and indirect evidence .

The result is not valid .

1.13 Study total 2933 UC patients were included in this meta - analysis .
95 % CI 0.87 - 1.37 ;
P = 0.47 ) , infectivity ( OR = 1.10 ;
95 % CI 0.51 - 2.38 ;
P = 0.81 ) and non - infectious ( OR = 1.10 ;
95 % CI 0.76 - 1.59 ;
There was no significant correlation between postoperative complications ( P = 0.61 ) . The use of infliximab in the first 12 weeks may be a protective factor against infection ( OR = 0.43 ;
95 % CI 0.22 - 0.83 ;
P=0.01). No bias was found .

2.18 studies total 5769 CD patients were included in this meta - analysis .
95 % CI 1.04 - 2.02 ;
13 studies ( 2538 ) , infectivity ( OR = 1.47 ) ;
95 % CI 1.08 - 1.99 ;
10 studies ( 2 ) and non - infective ( OR = 2.29 ) ;
95 % CI 1.14 - 4.61 ;
There was a significant correlation between postoperative complications of 3 studies and 729 ( OR = 1.39 ) .
95 % CI0.85 - 2.27 ;
9 studies ( 3696 ) and secondary ( OR = 1.39 ;
95 % CI 0.57 - 3.40 ;
There was no significant difference in the incidence of complications in 5 studies ( 753 ) . No bias was found .

3.Fifteen patients with CD were included in the meta - analysis of this network . The biological agents were compared with placebo , 5 - aminosalicylic acid or immunosuppressive agents to more significantly reduce endoscopic and clinical relapse . Immunosuppressive agents were more effective in preventing endoscopic and clinical relapse than placebo , 5 - aminosalicylic acid or immunosuppressive agents , but had a higher incidence of adverse events . 5 - aminosalicylic acid was more effective in preventing clinical relapse than placebo and did not increase the incidence of adverse reactions .

Conclusion

Preoperatively , the use of infliximab does not affect early postoperative complications in patients with UC , but may slightly increase postoperative complications of CD patients and is primarily postoperative infection . 5 - aminosalicylic acid , immunosuppressive agents and biological agents are effective in preventing postoperative recurrence of CD . Biologics are among the most effective drugs among the three .

【学位授予单位】：第四军医大学
【学位级别】：博士
【学位授予年份】：2014
【分类号】：R574

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