英夫利西治疗重度溃疡性结肠炎2例

目的:探讨英夫利西治疗重度溃疡性结肠炎(UC)的安全性和有效性.方法:报道2例重度UC治疗中英夫利西的用法、疗效及安全性,并复习近年国内外相关文献,结果:1例患者在接受3次英夫利西5 mg/kg诱导缓解后并以相同剂量每8wk 1次维持治疗,输注5次后达到黏膜愈合.另l例患者应用英夫利西5 mg/kg效果欠佳,加量至10...     

英夫利昔单抗治疗难治性溃疡性结肠炎25例护理体会

2008年1月～2010年2月，我们采用英夫利昔单抗治疗难治性溃疡性结肠炎患者取得良好疗效。现将临床观察和护理体会总结如下。     

噻唑烷二酮类治疗溃疡性结肠炎疗效的荟萃分析

目的采用Meta分析方法对噻唑烷二酮类药物(罗格列酮、吡格列酮)治疗溃疡性结肠炎的疗效进行系统评价。方法以"噻唑烷二酮"、"罗格列酮"、"吡格列酮"、"溃疡性结肠炎"、"随机对照试验"为检索词,检索PubMed、CNKI、WanFang Data、CBM、Google数据库,并追溯参考文献进行全面的文献检索。根据纳入与排除标准筛选文献,提取数据并评价质量,用Review Manager 4.3软件进行Meta分析,同时进行敏感性分析及发表偏倚的评估。结果本研究共纳入文献6篇,经Meta分析,噻唑烷二酮类能明显降低溃疡性结肠炎的疾病活动评分(UCAI)(WMD=-0.92,95%CI:-1.17~-0.66,P0.00001);噻唑烷二酮类明显增加溃疡性结肠炎的有效缓解人数(OR=12.31,95%CI:1.71~88.74,P=0.01);噻唑烷二酮类药物能明显改善溃疡性结肠炎的组织学分级,尤其是0~Ⅰ级(OR=2.71,95%CI:1.55~4.72,P=0.0004)。失效安全数结果显示,发表偏倚较小。敏感性分析研究表明结果稳定可靠。结论噻唑烷二酮类药物能显著提高溃疡性结肠炎的临床疗效。     

英夫利昔治疗溃疡性结肠炎临床疗效的荟萃分析

目的采用荟萃分析的方法,探讨英夫利昔(Infliximab,IFX)治疗溃疡性结肠炎(ulcerative colitis,UC)的疗效。方法全面检索并收集研究IFX治疗UC的临床随机对照试验。纳入7篇文献,共有7个随机对照实验(RCT)。质量评价、独立提取资料后以RevMan 4.2分析。结果荟萃分析显示:比较IFX与安慰剂治疗UC的长期、短期疗效,结果均有显著差异。比较IFX 5 mg、10mg与安慰剂组短期、长期的疗效,结果有显著差异。IFX的短期及长期疗效与激素相比,结果无显著差异。IFX与安慰剂的不良反应结果无显著差异。结论 IFX可以诱导UC的临床缓解及维持,而且对于难治性中重度UC,IFX可以使患者减少结肠切除率,提高生活质量。但是仍然需要大样本多中心的随机对照试验来进一步验证。     

重症溃疡性结肠炎的手术治疗

本文简介了重症溃疡性结肠炎手术治疗的指征、时机和方式,并评析了术后功能和生活质量,对临床工作具有指导意义。     

Ⅰ型干扰素治疗溃疡性结肠炎有效性的荟萃分析

目的:采用荟萃分析的方法对Ⅰ型干扰素治疗溃疡性结肠炎(ulcerative colitis,UC)的有效性进行系统评价.方法:检索Pub Med、EMBASE、CNKI中国期刊全文数据库、CBM中国生物医学文献数据库、万方数据库中所有关于Ⅰ型干扰素治疗UC的随机对照研究.应用比值比(odds ratio,OR)及其95%CI为疗效分析统计量,采用Rev Man5.1进行荟萃分析,比较干扰素与安慰剂治疗UC的有效缓解率及严重不良反应发生率.结果:共4篇文献纳入荟萃分析.结果显示,Ⅰ型干扰素治疗UC与安慰剂相比,有效缓解率无明显差异(OR=1.23,95%CI:0.76-2.01,P=0.40),严重不良反应发生率无明显差异(OR=1.44,95%CI:0.21-9.82,P=0.71).结论:应用Ⅰ型干扰素治疗UC患者,其疗效不优于安慰剂.     

抗肿瘤坏死因子α制剂治疗溃疡性结肠炎的荟萃分析

目的 根据现有临床研究评价抗TNFα制剂治疗溃疡性结肠炎(UC)的疗效与安全性.方法 检索Cochrane图书馆、EMBASE、PubMed、OVID数据库和中国知网、万方数据库、维普数据库中有关抗TNFa制剂[英夫利西单抗、阿达木单抗、塞妥珠单抗、依那西普、奥那西普、CDP571、CNI-1493、沙利度胺]治疗UC的RCT文献,采用Revman 5.0软件进行分析,并绘制漏斗图评定有无发表偏倚.结果 共9项RCT研究符合纳入标准,共包括1226例UC患者,其中806例接受抗TNFα制剂治疗,420例接受安慰剂或其他对照药物治疗.荟萃分析显示,在短期应答、短期缓解、长期应答、长期缓解方面,抗TNFα制剂明显优于对照组,OR值分别为2.36(95%CI 1.34～4.15)、2.42(95%CI 1.22～4.81)、3.22(95%CI 2.28～4.55)、2.82(95%CI 1.91～4.16).与对照组相比,抗TNFα制剂可以降低结肠切除率,OR值为0.31(95%CI 0.20～0.48);但在结肠黏膜愈合方面[OR值为1.59(95%CI 0.91～2.78)]及生活质量方面[炎症性肠病问卷(IBDQ)评分的加权均数差(WMD)为24.00(95%CI为-0.95～48.95)],两组的差异均无统计学意义.在安全性方面,两组不良反应发生率相似,OR值为1.07(95%CI0.55～2.09,P=0.84),但抗TNFα制剂的重度不良反应发生率明显低于对照组,OR值为0.65(95%CI 0.48～0.89).各计数资料观察指标的漏斗图均基本呈现下宽上窄、左右对称的图形,提示无发表偏倚.结论 抗TNFα制剂对于常规药物治疗无效的中、重度UC有较好的疗效,可以诱导UC短期应答,降低结肠切除率,并可维持长期的临床应答与临床缓解,严重不良反应的发生率较低,但抗TNFα制剂未能提高UC患者的生活质量与黏膜愈合率.

Abstract：

Objective To pool the data of studies and evaluate the efficacy and safety of TNFα blocking agents in the treatment of ulcerative colitis(UC).Methods The randomized clinical trials(RCT)that compared the efficacy or safety of TNFα in the treatment of UC were researched from Pubmed. OVID. EMBASE. Cochrane library, CNKI, Wanfang data and VIP Chinese Scientific and Technologic Periodical Database. Statistical heterogeneity between trials was evaluated by Revman 5.0 and was considered to exist when P＜0.1.Heterogeneity of the included articles was tested. which was used to select proper effect model to calculate. Publication bias was investigated through visual inspection of funnel plots. Results Nine RCT including 1226 cases were analyzed. Eight hundred and six cases had received TNFα treatment and 420cases had received placebo or glucocorticoid treatment. Compared with placebo or glucocorticoid groups, TNFα group achieved significantly higher rates of short-term clinical response, short-term clinical remission, long-term clinical response.10ng-term clinical remission and the total OR were 2.36(95%C,1.34-4.15),2.42(95%CI 1.22-4.81).3.22(95%CI2.28-4.55)and 2.82(95%CI1.91-4.16)respectively. TNFα group was less likely to undergo colectomy than placebo group and the total OR was 0.31(95%CI0.20-0.48).TNFα could not improve the mucosal healing and quality of lire. No significant difference was found in adverse effect between TNFα group and placebo or glueoeortieoid group(OR=1.07(95%CI0.55-2.09,P=0.84)).The rate of serious adverse effect in TNFα group was less than placebo or glueoeorticoid groups (OR=0.65,95%CI0.48-0.89,P=0.007).Inspection of the funnel plots for all dichotomous data measures had not revealed evidence of publication bias. Conclusions Patients with moderately to severely active UC treated with TNFαhave effective clinical response and clinical remission and are less likely to undergo colectomy than those receiving placebo or glucocorticoid. TNFα treatment is safe for UC but can not improve the mucosal healing and quality of life. Large-scale, high-quality RCTs ale needed to confirm or refuse the available evidence.     

阿达木单抗治疗溃疡性结肠炎的研究进展

阿达木单抗作为一种新型的抗肿瘤坏死因子α(TNF-α)制剂,已有临床试验证实其对中-重度溃疡性结肠炎有良好的治疗效果。阿达木单抗具有起效快、临床缓解率和黏膜愈合率高及安全性高等优点。本文主要对阿达木单抗的作用机制、疗效、药物代谢动力学、安全性及与其他抗TNF-α制剂的比较作一概述,以期为临床决策提供参考。     

抗肿瘤坏死因子α制剂治疗溃疡性结肠炎的荟萃分析

Objective To pool the data of studies and evaluate the efficacy and safety of TNFα blocking agents in the treatment of ulcerative colitis(UC).Methods The randomized clinical trials(RCT)that compared the efficacy or safety of TNFα in the treatment of UC were researched from Pubmed. OVID. EMBASE. Cochrane library, CNKI, Wanfang data and VIP Chinese Scientific and Technologic Periodical Database. Statistical heterogeneity between trials was evaluated by Revman 5.0 and was considered to exist when P＜0.1.Heterogeneity of the included articles was tested. which was used to select proper effect model to calculate. Publication bias was investigated through visual inspection of funnel plots. Results Nine RCT including 1226 cases were analyzed. Eight hundred and six cases had received TNFα treatment and 420cases had received placebo or glucocorticoid treatment. Compared with placebo or glucocorticoid groups, TNFα group achieved significantly higher rates of short-term clinical response, short-term clinical remission, long-term clinical response.10ng-term clinical remission and the total OR were 2.36(95%C,1.34-4.15),2.42(95%CI 1.22-4.81).3.22(95%CI2.28-4.55)and 2.82(95%CI1.91-4.16)respectively. TNFα group was less likely to undergo colectomy than placebo group and the total OR was 0.31(95%CI0.20-0.48).TNFα could not improve the mucosal healing and quality of lire. No significant difference was found in adverse effect between TNFα group and placebo or glueoeortieoid group(OR=1.07(95%CI0.55-2.09,P=0.84)).The rate of serious adverse effect in TNFα group was less than placebo or glueoeorticoid groups (OR=0.65,95%CI0.48-0.89,P=0.007).Inspection of the funnel plots for all dichotomous data measures had not revealed evidence of publication bias. Conclusions Patients with moderately to severely active UC treated with TNFαhave effective clinical response and clinical remission and are less likely to undergo colectomy than those receiving placebo or glucocorticoid. TNFα treatment is safe for UC but can not improve the mucosal healing and quality of life. Large-scale, high-quality RCTs ale needed to confirm or refuse the available evidence.     

抗肿瘤坏死因子α制剂治疗溃疡性结肠炎的荟萃分析

Objective To pool the data of studies and evaluate the efficacy and safety of TNFα blocking agents in the treatment of ulcerative colitis(UC).Methods The randomized clinical trials(RCT)that compared the efficacy or safety of TNFα in the treatment of UC were researched from Pubmed. OVID. EMBASE. Cochrane library, CNKI, Wanfang data and VIP Chinese Scientific and Technologic Periodical Database. Statistical heterogeneity between trials was evaluated by Revman 5.0 and was considered to exist when P＜0.1.Heterogeneity of the included articles was tested. which was used to select proper effect model to calculate. Publication bias was investigated through visual inspection of funnel plots. Results Nine RCT including 1226 cases were analyzed. Eight hundred and six cases had received TNFα treatment and 420cases had received placebo or glucocorticoid treatment. Compared with placebo or glucocorticoid groups, TNFα group achieved significantly higher rates of short-term clinical response, short-term clinical remission, long-term clinical response.10ng-term clinical remission and the total OR were 2.36(95%C,1.34-4.15),2.42(95%CI 1.22-4.81).3.22(95%CI2.28-4.55)and 2.82(95%CI1.91-4.16)respectively. TNFα group was less likely to undergo colectomy than placebo group and the total OR was 0.31(95%CI0.20-0.48).TNFα could not improve the mucosal healing and quality of lire. No significant difference was found in adverse effect between TNFα group and placebo or glueoeortieoid group(OR=1.07(95%CI0.55-2.09,P=0.84)).The rate of serious adverse effect in TNFα group was less than placebo or glueoeorticoid groups (OR=0.65,95%CI0.48-0.89,P=0.007).Inspection of the funnel plots for all dichotomous data measures had not revealed evidence of publication bias. Conclusions Patients with moderately to severely active UC treated with TNFαhave effective clinical response and clinical remission and are less likely to undergo colectomy than those receiving placebo or glucocorticoid. TNFα treatment is safe for UC but can not improve the mucosal healing and quality of life. Large-scale, high-quality RCTs ale needed to confirm or refuse the available evidence.     

英夫力西单抗治疗难治性溃疡性结肠炎

目的分析14例英夫力西治疗难治性中重度溃疡性结肠炎的临床资料,探索英夫力西治疗国人溃疡性结肠炎的效果和安全性。方法对我院2006年-2011年经常规治疗失败的14例难治性中重度溃疡性结肠炎患者,行英夫力西单抗治疗,分别于0、2、6周按5 mg/kg全身用药,以后每8周给药1次,个别患者因用药效果、病情变化等增加了用药剂量或缩短了用药间隔。分析英夫力西单抗治疗8周有效率和缓解率,随访30周、54周缓解率及安全性等。结果治疗8周有效率为42.9%,缓解率为42.9%,无效率为14.3%;随访30周、54周缓解率分别为57.1%和42.3%。有2例患者达到黏膜愈合,至今分别随访35个月和28个月,病情均无复发。不良反应发生率为28.6%,无严重或危及生命的不良反应发生。随访54周,有效组和无效组前两次英夫力西单抗治疗有效者所占比例差异有统计学意义(P=0.015)。结论应用英夫力西治疗14例难治性中重度溃疡性结肠炎,取得了良好的治疗效果,前两次治疗有效可预示远期治疗效果好,近期的药物不良反应不影响程序性治疗的进行。英夫力西单抗可作为国人难治性溃疡性结肠炎的挽救治疗方法。     

Takayasu arteritis developing during treatment of ulcerative colitis with infliximab

A 22-year-old female with ulcerative colitis that was successfully treated with infliximab (IFX), and remained stable following tapered discontinuation of prednisolone, developed anterior neck pain and elevation of C-reactive protein following her fourth administration of IFX. She was diagnosed with Takayasu arteritis (TA) based on neck ultrasound and computed tomography angiography. This is the first report describing the development of TA during treatment of UC with IFX.     

Use of infliximab in the prevention and delay of colectomy in severe steroid dependant and refractory ulcerative colitis

AIM： To determine if infliximab can prevent or delay surgery in refractory ulcerative colitis （UC）. METHODS： UC patients who failed to have their disease controlled with conventional therapies and were to undergo colectomy if infliximab failed to induce a clinical improvement were reviewed. Patients were primarily treated with a single 5 mg/kg infliximab dose. The Colitis Activity Index （CAI） was used to determine response and remission. Data of 8 wk response and colectomy rates at 6 mo and 12 mo were collected. RESULTS： Fifteen patients were included, 7 with UC unresponsive or intolerant to Ⅳ hydrocortisone, and 8 with active disease despite oral steroids （all but one with therapeutic dosage and duration of immunomodulation）. All the Ⅳ hydrocortisone-resistant/intolerant patients had been on azathioprine/6-MP 〈 8 wk. At 8 wk, infliximab induced a response in 86.7% （13/15） with 40% in remission （6/15）. Within 6 mo of treatment 26.7% （4/15） had undergone colectomy and surgery was avoided in 46.6% （7/15） at 12 mo. The colectomy rate at 12 mo in those on immunomodulatory therapy 〈 8 wk at time of infliximab was 12.5% （1/8） compared with 100% （7/7） in patients who were on long-term maintenance immunomodulators （P 〈 0.02）. CONCLUSION： Infliximab prevented colectomy due to active disease in immunomodulatory-na？ve, refractory UC patients comparable to the use of Cyclosporine. In patients, however, on effective dosage and duration of immunomodulation at time of infliximab therapy colectomy was not avoided.     

Efficacy of infliximab in acute severe ulcerative colitis:A single-centre experience

AIM:To suggest infliximab(IFX) is effective for acute severe ulcerative colitis,from real-life clinical practice.METHODS:All patients receiving IFX for the treatment of acute severe ulcerative colitis in a single centre were included.Data were extracted from clinical records in order to assess response to IFX therapy.The primary endpoint was colectomy-free survival,and secondary outcomes included glucocorticosteroid-free remission and safety,which was evaluated by recording deaths and adverse events.Demographic and clinical characteristics of those who underwent colectomy and those who were colectomy-free,both at discharge from their index admission,and during follow-up after an initial response to IFX were compared.RESULTS:Forty-four patients(16 females,mean age 36 years) received IFX between May 2006 and January 2012 for acute severe ulcerative colitis.The median duration of follow-up post-first infusion was 396 d(interquartile range = 173-828 d).There were 21(47.7%) patients with < 1 year of follow-up,10(22.7%) with 1 years to 2 years of follow-up,and 13(29.5%) with > 2 years of follow-up post-first infusion of IFX.Overall,35(79.5%) responded to IFX,avoiding colectomy during their index admission,29(65.9%) were colectomyfree at last point of follow-up(median follow-up 396 d),and 25(56.8%) were in glucocorticosteroid-free remission at end of follow-up.There was one death from post-operative sepsis,20 d after a single IFX infusion.Colectomy rates were generally lower among those "bridging" to thiopurine.Of 18 patients "bridged" to thiopurine therapy,17(94.4%) were colectomyfree,and 15(83.3%) were in glucocorticosteroid-free remission at study end.No predictors of response were identified.CONCLUSION:IFX is effective for acute severe ulcerative colitis in real-life clinical practice.Two-thirds of patients avoided colectomy,and more than 50% were in glucocorticosteroid-free remission.     

Treatment of severe steroid refractory ulcerative colitis

Although systemic steroids are highly efficacious in ulcerative colitis （UC）, failure to respond to steroids still poses an important challenge to the surgeon and physician alike. Even if the life time risk of a fulminant UC flare is only 20%, this condition is potentially life threatening and should be managed in hospital. If patients fail 3 to 5 d of intravenous corticosteroids and optimal supportive care, they should be considered for any of three options： intravenous cyclosporine （2 mg/kg for 7 d, and serum level controlled）, infliximab （5 mg/kg Ⅳ, 0-2-6 wk） or total colectomy. The choice between these three options is a medicalsurgical decision based on clinical signs, radiological and endoscopic findings and blood analysis （CRP, serum albumin）. Between 65 and 85% of patients will initially respond to cyclosporine and avoid colectomy on the short term. Over 5 years only 50% of initial responders avoid colectomy and outcomes are better in patients naive to azathioprine （bridging strategy）. The data on infliximab as a medical rescue in fulminant colitis are more limited although the efficacy of this anti tumor necrosis factor （TNF） monoclonal antibody has been demonstrated in a controlled trial. Controlled data on the comparative efficacy of cyclosporine and infliximab are not available at this moment. Both drugs are immunosuppressants and are used in combination with steroids and azathioprine, which infers a risk of serious, even fatal, opportunistic infections. Therefore, patients not responding to these agents within 5-7 d should be considered for colectomy and responders should be closely monitored for infections.     

Infliximab to treat severe ulcerative colitis

A 48-year-old female with severe ulcerative colitis refractory to conventional therapy was referred to our facility for management. The patient showed extensive ulcerative colitis since the age of 20 years and had failed therapy with 5-aminosalicylic acid agents and azathioprine. The disease remained active despite treatment with steroids and cyclosporine. The clinical and endoscopic parameters were consistent with severe disease. Infectious precipitants were ruled out. Given the severity of the disease and in order to avoid a colectomy, we started the patient on infliximab therapy. A dramatic clinical and endoscopic response was observed and she remained in remission at the end of a 1-year follow-up period. We discuss findings in the literature regarding the use of infliximab therapy in patients with ulcerative colitis who have failed steroids and cyclosporine.     

Early aggressive therapy for severe extensive ulcerative colitis

The current ulcerative colitis （UC） treatment algorithm involves a step-up therapeutic strategy, mainly aiming at inducing and maintaining its clinical remission. Although this therapeutic strategy may seem to be cost-efficient and reduce the risk of side effects, recent trials and case reports have shown that top-down therapy using infliximab induces a rapid clinical response, enhances patient quality of life, promotes mucosal healing, reduces surgeries and indirect cost of treatment for patients with severe UC. Moreover, since long-term treatment with infliximab is safe and well tolerated, early aggressive top-down therapeutic strategy may be a more effective approach, at least in a subgroup of severe extensive UC patients.     

Management of acute severe ulcerative colitis

The management strategy of acute severe ulcerative colitis has evolved over the past decade from being entirely restricted to twin choices of intravenous steroids or colectomy to include colon rescue therapies like cyclosporin as well as infliximab. However it still remains a medical emergency requiring hospitalization and requires care from a multidisciplinary team comprising of a gastroenterologist and a colorectal surgeon. The frame shift in management has been the emphasis on time bound decision making with an attempt to curtail the mortality rate to below 1%. Intravenous corticosteroids are the mainstay of therapy. Response to steroids should be assessed at day 3 of admission and partial/non-responders should be considered for alternative medical therapy/surgery. Medical rescue therapies include intravenous cyclosporin and infliximab. Cyclosporin is administered in a dose of 2 mg/kg per day and infliximab is administered as a single dose intravenous infusion of 5 mg/kg. Approximately 75% patients have short term and 50% patients have long term response to cyclosporin. Long term response to cyclosporin is improved in patients who are thiopurine naïve and are started on thiopurines on day 7. Infliximab also has a response rate of approximately 70% in short term and 50% in long term. Both cyclosporin and infliximab are equally efficacious medical rescue therapies as demonstrated in a recent randomized control trial. Patients not responding to infliximab or cyclosporin should be considered for colectomy.