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

【摘要】：【背景】 炎癥性腸�。╥nflammatory bowel disease，IBD）主要包括潰瘍性結(jié)腸炎（ulcerativecolitis，UC）和克羅恩病（Crohn’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(jìn)展，IBD患者仍然在其患病過(guò)程中不得不面臨手術(shù)。隨著TNF拮抗劑在臨床中的大量使用，其圍手術(shù)期的安全性成為臨床醫(yī)生關(guān)注的焦點(diǎn)。本課題運(yùn)用meta分析方法，全面梳理和薈萃現(xiàn)有臨床證據(jù)，系統(tǒng)評(píng)價(jià)TNF拮抗劑對(duì)IBD術(shù)后并發(fā)癥的影響及其預(yù)防術(shù)后復(fù)發(fā)的作用。 【目的】 1．評(píng)估UC患者中術(shù)前英夫利希單抗的治療對(duì)腹部手術(shù)早期預(yù)后的臨床安全性和有效性。 2．評(píng)估接受腹部手術(shù)的CD患者中術(shù)前英夫利希單抗的使用對(duì)早期術(shù)后并發(fā)癥的影響。 3．通過(guò)網(wǎng)絡(luò)meta分析方法比較5-氨基水楊酸、免疫抑制劑和生物制劑預(yù)防CD術(shù)后復(fù)發(fā)的療效。 【方法】 1．通過(guò)搜索PubMed和Embase數(shù)據(jù)庫(kù)篩選比較術(shù)前接受或沒(méi)有接受英夫利希單抗的UC患者術(shù)后并發(fā)癥的觀察性對(duì)照研究。主要觀察終點(diǎn)為總體并發(fā)癥發(fā)生率。次要觀察終點(diǎn)包括感染性和非感染性并發(fā)癥。我們計(jì)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(guò)搜索PubMed和Embase數(shù)據(jù)庫(kù)篩選比較術(shù)前接受或沒(méi)有接受英夫利希單抗的CD患者術(shù)后并發(fā)癥的對(duì)照研究。使用隨機(jī)效應(yīng)模型的meta分析計(jì)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(guò)搜索PubMed、Embase和Cochrane圖書(shū)館等數(shù)據(jù)庫(kù)（截止2013年11月）來(lái)篩選以安慰劑作對(duì)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(lèi)藥物預(yù)防CD術(shù)后復(fù)發(fā)的隨機(jī)試驗(yàn)。主要觀察終點(diǎn)為預(yù)防內(nèi)鏡復(fù)發(fā)的療效，次要觀察終點(diǎn)包括臨床復(fù)發(fā)和不良事件。運(yùn)用混合效應(yīng)比較模型實(shí)施貝葉斯網(wǎng)絡(luò)meta分析，以同時(shí)合并直接和間接證據(jù)。 【結(jié)果】 1．13項(xiàng)研究合計(jì)2933名UC患者納入本項(xiàng)meta分析。術(shù)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(shù)后并發(fā)癥之間均無(wú)顯著相關(guān)性。術(shù)前12周內(nèi)使用英夫利希單抗可能是抗感染的保護(hù)性因素（OR=0.43；95%CI0.22-0.83；P=0.01）。沒(méi)有發(fā)現(xiàn)發(fā)表偏倚。 2．18項(xiàng)研究合計(jì)5769名CD患者納入本項(xiàng)meta分析。術(shù)前英夫利希單抗治療與總體（OR=1.45；95%CI1.04-2.02；13項(xiàng)研究，2538人）、感染性（OR=1.47；95%CI1.08-1.99；10項(xiàng)研究，2116人）和非感染性（OR=2.29；95%CI1.14-4.61；3項(xiàng)研究，729人）術(shù)后并發(fā)癥均有顯著相關(guān)性。英夫利希單抗和對(duì)照組之間在主要（OR=1.39；95%CI0.85-2.27；9項(xiàng)研究，3696人）和次要（OR=1.39；95%CI0.57-3.40；5項(xiàng)研究，753人）并發(fā)癥發(fā)生率上并無(wú)顯著性差異。沒(méi)有發(fā)現(xiàn)發(fā)表偏倚。 3．15項(xiàng)試驗(yàn)合計(jì)1507名CD患者納入本項(xiàng)網(wǎng)絡(luò)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(nèi)鏡和臨床復(fù)發(fā)。免疫抑制劑較5-氨基水楊酸或安慰劑能更有效地預(yù)防內(nèi)鏡和臨床復(fù)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(yù)防臨床復(fù)發(fā)，且不增加不良反應(yīng)發(fā)生率。 【結(jié)論】 術(shù)前英夫利希單抗的使用不會(huì)影響UC患者的早期術(shù)后并發(fā)癥，但會(huì)輕微增加CD患者的術(shù)后并發(fā)癥，，且主要是術(shù)后感染。5-氨基水楊酸、免疫抑制劑和生物制劑都能有效預(yù)防CD術(shù)后復(fù)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(xué)位授予單位】：第四軍醫(yī)大學(xué)
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2014
【分類(lèi)號(hào)】：R574

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