本文選題：英夫利希單抗　切入點：TNF拮抗劑　出處：《第四軍醫(yī)大學》2014年博士論文

【摘要】：【背景】 炎癥性腸病（inflammatory bowel disease，IBD）主要包括潰瘍性結腸炎（ulcerativecolitis，UC）和克羅恩�。–rohn’s disease，CD）。雖然以腫瘤壞死因子（tumor necrosisfactor，TNF）拮抗劑為代表的生物制劑在IBD的治療中取得重要進展，IBD患者仍然在其患病過程中不得不面臨手術。隨著TNF拮抗劑在臨床中的大量使用，其圍手術期的安全性成為臨床醫(yī)生關注的焦點。本課題運用meta分析方法，全面梳理和薈萃現有臨床證據，系統(tǒng)評價TNF拮抗劑對IBD術后并發(fā)癥的影響及其預防術后復發(fā)的作用。 【目的】 1．評估UC患者中術前英夫利希單抗的治療對腹部手術早期預后的臨床安全性和有效性。 2．評估接受腹部手術的CD患者中術前英夫利希單抗的使用對早期術后并發(fā)癥的影響。 3．通過網絡meta分析方法比較5-氨基水楊酸、免疫抑制劑和生物制劑預防CD術后復發(fā)的療效。 【方法】 1．通過搜索PubMed和Embase數據庫篩選比較術前接受或沒有接受英夫利希單抗的UC患者術后并發(fā)癥的觀察性對照研究。主要觀察終點為總體并發(fā)癥發(fā)生率。次要觀察終點包括感染性和非感染性并發(fā)癥。我們計算合并比值比（odds ratio，OR）和95%可信區(qū)間（confidence interval，CI）作為薈萃變量。 2．通過搜索PubMed和Embase數據庫篩選比較術前接受或沒有接受英夫利希單抗的CD患者術后并發(fā)癥的對照研究。使用隨機效應模型的meta分析計算合并比值比和95%可信區(qū)間，薈萃變量包括總體并發(fā)癥發(fā)生率以及主要、次要、感染性和非感染性并發(fā)癥。 3．通過搜索PubMed、Embase和Cochrane圖書館等數據庫（截止2013年11月）來篩選以安慰劑作對照或者兩兩比較5-氨基水楊酸、免疫抑制劑和生物制劑三類藥物預防CD術后復發(fā)的隨機試驗。主要觀察終點為預防內鏡復發(fā)的療效，次要觀察終點包括臨床復發(fā)和不良事件。運用混合效應比較模型實施貝葉斯網絡meta分析，以同時合并直接和間接證據。 【結果】 1．13項研究合計2933名UC患者納入本項meta分析。術前英夫利希單抗治療與總體（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）術后并發(fā)癥之間均無顯著相關性。術前12周內使用英夫利希單抗可能是抗感染的保護性因素（OR=0.43；95%CI0.22-0.83；P=0.01）。沒有發(fā)現發(fā)表偏倚。 2．18項研究合計5769名CD患者納入本項meta分析。術前英夫利希單抗治療與總體（OR=1.45；95%CI1.04-2.02；13項研究，2538人）、感染性（OR=1.47；95%CI1.08-1.99；10項研究，2116人）和非感染性（OR=2.29；95%CI1.14-4.61；3項研究，729人）術后并發(fā)癥均有顯著相關性。英夫利希單抗和對照組之間在主要（OR=1.39；95%CI0.85-2.27；9項研究，3696人）和次要（OR=1.39；95%CI0.57-3.40；5項研究，753人）并發(fā)癥發(fā)生率上并無顯著性差異。沒有發(fā)現發(fā)表偏倚。 3．15項試驗合計1507名CD患者納入本項網絡meta分析。生物制劑較安慰劑、5-氨基水楊酸或免疫抑制劑能更大幅度更顯著地減少內鏡和臨床復發(fā)。免疫抑制劑較5-氨基水楊酸或安慰劑能更有效地預防內鏡和臨床復發(fā)，但有更高的不良事件發(fā)生率。5-氨基水楊酸比安慰劑更更有效地預防臨床復發(fā)，且不增加不良反應發(fā)生率。 【結論】 術前英夫利希單抗的使用不會影響UC患者的早期術后并發(fā)癥，但會輕微增加CD患者的術后并發(fā)癥，，且主要是術后感染。5-氨基水楊酸、免疫抑制劑和生物制劑都能有效預防CD術后復發(fā)。生物制劑是三者中最有效的藥物。
[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 .

【學位授予單位】：第四軍醫(yī)大學
【學位級別】：博士
【學位授予年份】：2014
【分類號】：R574

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