本文關(guān)鍵詞：英夫利西單用和聯(lián)合硫唑嘌呤誘導(dǎo)及維持克羅恩病患者深度緩解的療效分析　出處：《南方醫(yī)科大學(xué)》2016年碩士論文　論文類型：學(xué)位論文

  更多相關(guān)文章： 克羅恩病 英夫利西 硫唑嘌呤 臨床緩解 黏膜愈合 深度緩解

【摘要】：背景和目的：克羅恩病(Crohn's disease, CD)是一種可累及全消化道的慢性炎癥性疾病。其治療藥物主要有5-氨基水楊酸(5-ASA)、糖皮質(zhì)激素、免疫抑制劑(硫唑嘌呤、巰嘌呤、甲氨蝶呤)、生物制劑(腫瘤壞死因子拮抗劑)。伴隨著新型抗TNF-α藥物的生產(chǎn)和發(fā)展、內(nèi)鏡技術(shù)的進(jìn)展和對(duì)CD疾病認(rèn)識(shí)的深入,CD的治療目標(biāo)也逐步發(fā)生改變,由臨床緩解、黏膜愈合發(fā)展到深度緩解和組織緩解。其中,深度緩解已應(yīng)用于描述接受免疫抑制劑或TNF-α拮抗劑或兩者聯(lián)合治療的CD患者沒有臨床癥狀和客觀炎癥表現(xiàn)的狀態(tài)(定義為克羅恩病活動(dòng)指數(shù)小于150分,并內(nèi)鏡下緩解)。國(guó)外已有研究證實(shí)英夫利西(Infliximab, IFX)可以誘導(dǎo)和維持CD患者獲得深度緩解。然而,目前我國(guó)關(guān)于IFX對(duì)于CD患者獲得深度緩解的作用和意義報(bào)道甚少,并且關(guān)于IFX單藥治療和IFX聯(lián)合硫唑嘌呤(Azathioprine, AZA)治療對(duì)CD患者獲得深度緩解的療效比較方面更缺乏大樣本的相關(guān)臨床研究數(shù)據(jù)。同時(shí)也尚不清楚升階梯治療方案和降階梯治療方案對(duì)深度緩解療效等影響�；谝陨涎芯勘尘�,本研究通過回顧南方醫(yī)科大學(xué)南方醫(yī)院消化內(nèi)科2011年5月至2015年5月期間住院診治確診為CD并且接受IFX單藥或者IFX+AZA兩藥聯(lián)合治療的82例患者的人口學(xué)特點(diǎn)、臨床表現(xiàn)、內(nèi)鏡表現(xiàn)、藥物治療方案和治療效果等臨床資料,分析比較IFX單藥治療和IFX+AZA兩藥聯(lián)合治療對(duì)誘導(dǎo)和維持CD患者臨床緩解、黏膜愈合和深度緩解的療效及安全性,同時(shí)分析升階梯和降階梯治療對(duì)誘導(dǎo)和維持CD患者深度緩解的影響,從而為CD的治療提供更多的依據(jù)。對(duì)象與方法：1.研究對(duì)象選取2011年5月至2015年5月期間在南方醫(yī)科大學(xué)南方醫(yī)院消化內(nèi)科住院診治確診為CD并且接受IFX單藥或者IFX+AZA兩藥聯(lián)合治療的患者為研究對(duì)象�；颊逤D的診斷綜合了臨床表現(xiàn)、影像學(xué)、消化內(nèi)鏡、病理組織學(xué)檢查及隨訪觀察結(jié)果等,并且符合中華醫(yī)學(xué)會(huì)消化病學(xué)分會(huì)炎癥性腸病協(xié)作組《炎癥性腸病診斷與治療的共識(shí)意見(2012年·廣州)》有關(guān)CD的診斷標(biāo)準(zhǔn)。2.研究方法按照治療方式的不同,將患者分為IFX單藥治療組和IFX+AZA兩藥聯(lián)合治療組。采用回顧性調(diào)查方法,記錄并統(tǒng)計(jì)兩組患者的臨床資料,并計(jì)算患者克羅恩病活動(dòng)度指數(shù)(CDAI)、臨床緩解率、克羅恩病簡(jiǎn)化內(nèi)鏡評(píng)分(SES-CD)、黏膜愈合率、深度緩解率以及不良反應(yīng)率。3.統(tǒng)計(jì)學(xué)處理采用SPSS20.0統(tǒng)計(jì)學(xué)軟件進(jìn)行分析,正態(tài)分布計(jì)量資料以x±s表示,計(jì)數(shù)資料以n和%表示;治療前后的比較采用t檢驗(yàn)；非正態(tài)分布的計(jì)量資料以中位數(shù)(M)[下四分位數(shù)(QL),上四分位數(shù)(QU)]表示,治療前后的比較采用Wilcoxon非參數(shù)符號(hào)秩檢驗(yàn)進(jìn)行比較；率的比較使用卡方檢驗(yàn)或Fisher確切概率法。P0.05為差異有統(tǒng)計(jì)學(xué)意義。結(jié)果：1.患者分組情況2011年5月至2015年5月在南方醫(yī)科大學(xué)南方醫(yī)院確診CD并接受IFX治療的患者共計(jì)82例,其中男54例,女28例,確診年齡12-57歲,平均確診年齡為(26.0±10.5)歲,其中79例患者為中度克羅恩病,3例患者為重度克羅恩病。根據(jù)治療方案不同,患者分為IFX組和IFX+AZA組,其中48.8%(40/82)為IFX組,51.2%(42/82)為IFX+AZA組。2.兩組患者基本情況比較IFX組40例患者中男性28例,女性12例,平均確診年齡為(27.3±9.5)歲,平均治療年齡為(28.0±9.6)歲,平均BMI為(18.5±3.1)kg/m2,既往有CD相關(guān)腸道手術(shù)者占22.5%(9/40),有腸外表現(xiàn)者占15.0%(6/40),其中2例為口腔潰瘍,4例為關(guān)節(jié)痛。IFX+AZA組42例患者中男性26例,女性16例,平均確診為(24.8±11.2)歲,平均治療年齡為(25.4±11.3)歲,平均BMI為(17.5±2.7)kg/m2,既往有CD相關(guān)腸道手術(shù)者占19.0%(8/42),有腸外表現(xiàn)者占19.0%(8/42),其中1例為關(guān)節(jié)痛并結(jié)節(jié)性紅斑,1例為關(guān)節(jié)痛并雙側(cè)眼鞏膜炎,3例為口腔潰瘍,3例為關(guān)節(jié)痛。兩組患者的性別、年齡、腸外表現(xiàn)等資料對(duì)比差異無統(tǒng)計(jì)學(xué)意義(P0.05),具有可比性。3.兩組患者實(shí)驗(yàn)室指標(biāo)筆體重指數(shù)比較第14周和第30周時(shí),IFX組和IFX+AZA組患者的WBC水平、CRP水平和ESR水平均較治療前明顯下降,患者炎癥得到控制；而兩組患者的HGB水平、ALB水平和體重指數(shù)均較治療前升高,患者營(yíng)養(yǎng)狀態(tài)得到明顯改善。但兩組患者治療后組間實(shí)驗(yàn)室指標(biāo)和體重指數(shù)比較差異無統(tǒng)計(jì)學(xué)意義。4.兩組患者臨床緩解療效比較第14周時(shí),IFX組CDAI評(píng)分由[254.0(231.2,268.0]分下降為[87.5(55.5,118.0)]分,P0.05：IFX+AZA組CDAI評(píng)分由[256.0(231.7,346.7)]分下降為[85.0(49.8,121.0)]分,P0.05;但是兩組間CDAI評(píng)分差異無統(tǒng)計(jì)學(xué)意義(P0.05)。兩組的臨床緩解率分別為90.0%86/40 vs.83.3%85/42)P0.05,差異無統(tǒng)計(jì)學(xué)意義,但數(shù)據(jù)顯示IFX組的臨床緩解率高。第30周時(shí),IFX組CDAI評(píng)分由[254.0(231.2,268.0]分下降為[75.0(32.9,101.8)]分,P0.05；IFX+AZA組CDAI評(píng)分由[256.0(231.7,346.7)]分下降為[79.6(51.5,142.4)]分,P0.05：但是兩組間CDAI評(píng)分差異沒有統(tǒng)計(jì)學(xué)意義(P0.05)。兩組的臨床緩解率分別為92.5%87/40 vs.83.3%85/42)P0.05,差異無統(tǒng)計(jì)學(xué)意義,但數(shù)據(jù)顯示IFX組的臨床緩解率高。5.兩組患者黏膜愈合療效比較第14周時(shí),IFX組有22例患者復(fù)查內(nèi)鏡,SES-CD評(píng)分由[10.9(7.1,17.1)]分下降為[3.6(0,5.3)]分,P0.05；IFX+AZA組有33例患者復(fù)查內(nèi)鏡,SES-CD評(píng)分由[12.0(6.8,15.2)]分下降為[2.8(0,6.6)]分,P0.05；但是兩組間SES-CD評(píng)分比較差異沒有統(tǒng)計(jì)學(xué)意義(P0.05)；兩組的黏膜愈合率分別為：40.9%(9/22)vs.48.5%(16/33),P0.05,差異沒有統(tǒng)計(jì)學(xué)意義,但數(shù)據(jù)顯示IFX+AZA組黏膜愈合率較高。第30周時(shí),IFX組SES-CD評(píng)分由[7.9(5.7,11.6)]分下降為[0.6(0,5.5)]分,P0.05；IFX+AZA組SES-CD評(píng)分由[11.0(6.5,15.0)]分下降為[0.1(0,5.3)]分,P0.05；然而兩組間SES-CD評(píng)分比較差異沒有統(tǒng)計(jì)學(xué)意義(P0.05)：兩組的黏膜愈合率分別為：60.0%(24/40)vs.64.3%(27/42),P0.05,差異沒有統(tǒng)計(jì)學(xué)意義,但數(shù)據(jù)顯示IFX+AZA組黏膜愈合率較高。6.兩組患者深度緩解療效比較：6.1兩組患者深度緩解率比較第14周時(shí),IFX組有22例復(fù)查內(nèi)鏡,IFX+AZA組有33例復(fù)查內(nèi)鏡,兩組的深度緩解率分別為：36.4%(8/22)vs.45.5%(15/33),P0.05。第30周時(shí),兩組患者均復(fù)查內(nèi)鏡,兩組的深度緩解率分別為：57.5%(23/40)vs.59.5%(25/42),P0.05。兩組深度緩解率的差異沒有統(tǒng)計(jì)學(xué)意義,但數(shù)據(jù)顯示IFX+AZA組深度緩解率較高。第14周和第30周時(shí),IFX組和IFX+AZA組中,各組內(nèi)獲得深度緩解的患者中CRP水平5mg/L的比例明顯均高于未獲得深度緩解的患者。然而兩組患者組間比較差異無統(tǒng)計(jì)學(xué)意義。6.2早期獲得深度緩解與未獲得深度緩解療效分析根據(jù)患者第14周時(shí)深度緩解情況,將每組患者再分為早期獲得深度緩解組和早期未獲得深度緩解組。第30周時(shí),IFX組有87.5%(7/8)早期獲得深度緩解的患者在30周時(shí)維持深度緩解;IFX+AZA組有93.3%(14/15)早期獲得深度緩解的患者在30周時(shí)維持深度緩解。且IFX組和IFX+AZA組中早期獲得深度緩解的患者的CDAI評(píng)分、SES-CD評(píng)分、WBC水平、CRP水平和ESR水平均低于早期未獲得深度緩解的患者,而HGB水平、ALB水平和BMI值均高于早期未獲得深度緩解的患者,提示早期獲得深度緩解有利于控制炎癥和改善患者營(yíng)養(yǎng)狀態(tài)。6.3升或降階梯治療方案對(duì)深度緩解的影響IFX組有27.5%(11/40)患者采用升階梯治療方案,IFX+AZA組有28.6%(12/42)患者采用升階梯治療方案,在治療后第14周和第30周,IFX組中升階梯治療患者和降階梯治療患者的深度緩解率分別為[33.3%(2/6)vs.37.5%(6/16),P0.05]和[54.5%(6/11)vs.58.6%(17/29),P0.05]；第14周時(shí)IFX+AZA組中升階梯治療患者均未獲得深度緩解,而采用降階梯治療患者中有60.0%(15/25)獲得深度緩解率,第30周時(shí)IFX+AZA組中升階梯治療患者和降階梯治療患者的深度緩解率分別為41.7%(5/12)vs.66.7%(20/30),P0.05：數(shù)據(jù)顯示兩組患者組內(nèi)均是采用降階梯治療方案患者的深度緩解率高于采用升階梯治療方案的患者,但是差異無統(tǒng)計(jì)學(xué)意義。兩組組間比較差異也無統(tǒng)計(jì)學(xué)意義。7.不良反應(yīng)IFX組有25.0%(10/40)患者出現(xiàn)不良反應(yīng),IFX+AZA組有26.2%(11／42)患者出現(xiàn)不良反應(yīng),兩組不良反應(yīng)發(fā)生率比較差異沒有統(tǒng)計(jì)學(xué)意義。兩組患者均未出現(xiàn)其他嚴(yán)重不良反應(yīng)。結(jié)論：本次回顧性研究發(fā)現(xiàn),IFX和IFX+AZA兩種方法均可有效誘導(dǎo)和維持中度CD患者臨床緩解、黏膜愈合和深度緩解,兩組患者的臨床緩解率、黏膜愈合率和深度緩解率比較差異無統(tǒng)計(jì)學(xué)意義,但數(shù)據(jù)顯示IFX+AZA組的黏膜愈合率和深度緩解率均高于IFX組,IFX+AZA兩藥聯(lián)合治療可能在促進(jìn)黏膜愈合和深度緩解方面有更優(yōu)趨勢(shì)。并且,早期獲得深度緩解有助于患者炎癥控制和營(yíng)養(yǎng)改善,本研究發(fā)現(xiàn),降階梯治療方案有助于患者獲得深度緩解,可能有較好優(yōu)勢(shì)。
[Abstract]:Background and purpose: Crohn's disease (CD) is a chronic inflammatory disease that can involve the whole digestive tract. The drugs are mainly 5- aminosalicylic acid (5-ASA), corticosteroids, immunosuppressants (azathioprine, mercaptopurine, methotrexate), biological agents (tumor necrosis factor antagonist). Along with the production and development of new anti TNF- drugs, the progress of endoscopic technology and the recognition of CD disease, the therapeutic targets of CD have gradually changed, from clinical alleviation, mucosal healing to deep remission and tissue remission. Deep remission has been applied to describe the situation of CD patients who received immunosuppressive drugs or TNF- alpha antagonists or combination therapy without clinical symptoms and objective inflammatory manifestations (defined as Crohn disease activity index less than 150 points, and endoscopic remission). Studies have shown that Indira J Lici (Infliximab, IFX) can induce and maintain the depth remission of CD patients. However, at present our country about IFX for patients with CD depth relief function and significance of the report is very little, and on the IFX and IFX combined with azathioprine monotherapy (Azathioprine, AZA) after the treatment of CD with effective depth relief and lack of relevant clinical research data of large sample comparison. At the same time, it is not clear that the escalation treatment plan and the step down treatment plan on the effect of depth remission. Based on the above research background, this study by reviewing the South Hospital of Southern Medical University from May 2011 to May 2015 during the period of hospitalization were diagnosed as CD and received IFX monotherapy or IFX+AZA two drugs in the treatment of 82 cases of patients with the demographic characteristics, clinical manifestations, clinical data, endoscopic table of drug treatment and the treatment results were compared between IFX single drug IFX+AZA treatment and two drugs in the treatment of the efficacy and safety of induction and maintenance of clinical remission in patients with CD in remission, mucosal healing and depth, and analysis step up and step-down therapy effect on the induction and maintenance of remission in patients with CD depth, so as to provide more evidence for the treatment of CD. Participants and methods: 1. the subjects were selected from May 2011 to May 2015, who were diagnosed as CD in the Department of Gastroenterology, Nanfang Hospital of Southern Medical University, and were treated with IFX single or IFX+AZA two drugs. The diagnosis of CD the clinical manifestations, imaging, endoscopy and pathological examination and follow-up results, and in line with the branch of inflammatory bowel disease group "diagnosis and treatment of inflammatory bowel disease consensus on digestive diseases of Chinese Medical Association (2012 - Guangzhou)" diagnostic criteria for CD. 2. in accordance with the different methods of treatment, the patients were divided into IFX single drug treatment group and IFX+AZA two medicine group. The clinical data of two groups of patients were recorded and counted by retrospective investigation method, and the activity index (CDAI), clinical remission rate, Crohn disease simplified endoscopic score (SES-CD), mucosal healing rate, depth remission rate and adverse reaction rate were calculated. 3. statistical analysis using SPSS20.0 statistical software, the normal distribution of measurement data with x + s said the count data expressed in N and% compared with before and after treatment; t test; non normal distribution of measurement data with median (M) [four quantile (QL), four (the number of bits QU)] said, before and after treatment were compared by comparing the nonparametric Wilcoxon signed rank test; were compared using chi square test or Fisher exact probability method. The difference was statistically significant in P0.05. Results: 1. patients were grouped and treated by IFX from May 2011 to May 2015 in Nanfang Hospital of Southern Medical University diagnosed CD patients a total of 82 cases, male 54 cases, female 28 cases, with age 12-57 years old, the average age of diagnosis was (26 + 10.5) years old, among them 79 cases of Crohn's disease, 3 patients severe Crohn's disease. According to the different treatments, the patients were divided into group IFX and group IFX+AZA, of which 48.8% (40/82) was group IFX and 51.2% (42/82) was group IFX+AZA. The basic situation of the 2. patients in the two groups compared with IFX group of 40 patients, 28 were male, 12 females, the average age of diagnosis was (27.3 + 9.5) years old, the average age for the treatment of (28 + 9.6) years old, the average BMI (18.5 + 3.1) kg/m2, with a history of CD related intestinal surgery accounted for 22.5% (9/40), performance of parenteral accounted for 15% (6/40), including 2 cases of oral ulcer, 4 cases of joint pain. IFX+AZA group of 42 patients, male 26 cases, female 16 cases, average diagnosed (24.8 + 11.2) years old, the average age for the treatment of (25.4 + 11.3) years old, the average BMI (17.5 + 2.7) kg/m2, with a history of CD related intestinal surgery accounted for 19% (8/42), parenteral for performance 19% (8/42), including 1 cases of joint pain and erythema nodosum, 1 cases of joint pain and bilateral ocular scleritis, 3 cases of oral ulcer, 3 cases of joint pain. There was no significant difference in the sex, age, and expression of the two groups of patients (P0.05), which was comparable. 3. two groups of patients with laboratory indexes pen body mass index comparison of fourteenth and thirtieth weeks, IFX group and IFX+AZA group were WBC, CRP and ESR level were significantly decreased compared with before treatment, patients with inflammation under control; and the two group of patients with HGB and ALB levels and body mass index were higher than that before treatment, nutrition the state of patients improved obviously. However, there was no significant difference in the laboratory index and body mass index between the two groups after treatment. 4. of the two groups of patients with clinical remission compared to fourteenth weeks, IFX group CDAI score by [254.0 (231.2268.0] (55.5118.0)] decreased to [87.5, P0.05:IFX+AZA group CDAI score by [256.0 (231.7346.7)] decreased [85.0 (49.8121.0)], P0.05; but there was no significant difference of CDAI score between the two groups (P0.05). The clinical remission rate of the two groups was 90.0%86/40 vs.83.3%85/42) P0.05 respectively, the difference was not statistically significant, but the data showed that the clinical remission rate of the IFX group was high. At thirtieth weeks, IF
【學(xué)位授予單位】：南方醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2016
【分類號(hào)】：R574.62

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