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.     

Comparative efficacy of golimumab,infliximab, and adalimumab for moderately to severely active ulcerative colitis: a network meta-analysis accounting for differences in trial designs

Aim: To conduct a network meta-analysis (NMA) to establish the comparative efficacy of infliximab, adalimumab and golimumab for the treatment of moderately to severely active ulcerative colitis (UC). Design: A systematic literature search identified five randomized controlled trials for inclusion in the NMA. One trial assessed golimumab, two assessed infliximab and two assessed adalimumab. Outcomes included clinical response, clinical remission, mucosal healing, sustained clinical response and sustained clinical remission. Innovative methods were used to allow inclusion of the golimumab trial data given the alternative design of this trial (i.e., two-stage re-randomization). Results: After induction, no statistically significant differences were found between golimumab and adalimumab or between golimumab and infliximab. Infliximab was statistically superior to adalimumab after induction for all outcomes and treatment ranking suggested infliximab as the superior treatment for induction. Golimumab and infliximab were associated with similar efficacy for achieving maintained clinical remission and sustained clinical remission, whereas adalimumab was not significantly better than placebo for sustained clinical remission. Golimumab and infliximab were also associated with similar efficacy for achieving maintained clinical response, sustained clinical response and mucosal healing. Finally, golimumab 50 and 100 mg was statistically superior to adalimumab for clinical response and sustained clinical response, and golimumab 100 mg was also statistically superior to adalimumab for mucosal healing. Conclusion: The results of our NMA suggest that infliximab was statistically superior to adalimumab after induction, and that golimumab was statistically superior to adalimumab for sustained outcomes. Golimumab and infliximab appeared comparable in efficacy.     

Adalimumab versus infliximab for the treatment of moderate to severe ulcerative colitis in adult patients naïve to anti-TNF therapy: An indirect treatment comparison meta-analysis

ObjectiveTo compare the efficacy of adalimumab and infliximab for the treatment of moderate to severe ulcerative colitis using indirect treatment comparison meta-analysis.MethodsA systematic review and Bayesian indirect treatment comparison meta-analyses were performed for seven patient-important clinical outcomes at 8 weeks and 52 weeks. Odds ratio (OR) estimates and associated 95% credible intervals (CrIs) were produced.ResultsFive eligible RCTs informed clinical remission, response, mucosal healing, quality of life, colectomy, serious adverse events, and discontinuation due to adverse events at 8 weeks and 52 weeks. At 8 weeks of induction therapy, clinical remission (OR = 0.42, 95% CrI 0.17–0.97), clinical response (OR = 0.45, 95% CrI 0.23–0.89) and mucosal healing (OR = 0.46, 95% CrI 0.25–0.86) statistically favored infliximab. However, after 52 weeks of maintenance therapy OR estimates showed no significant difference between infliximab and adalimumab. For serious adverse events and discontinuations due to adverse events, adalimumab and infliximab were similar to placebo. Further, the indirect treatment comparison of adalimumab and infliximab yielded odds ratios close to 1.00 with wide credible intervals.ConclusionThe findings of this indirect treatment comparison meta-analysis suggest that both infliximab and adalimumab are superior to placebo in the treatment of moderate to moderately severe ulcerative colitis. While infliximab is statistically more effective than adalimumab in the induction of remission, response and mucosal healing at 8 weeks, infliximab and adalimumab are comparable in efficacy at 52 weeks of maintenance treatment.     

Ulcerative colitis patients in clinical remission demonstrate correlations between fecal immunochemical test results,mucosal healing,and risk of relapse

AIM: To assess the risk of relapse in ulcerative colitis(UC) patients in clinical remission using mucosal status and fecal immunochemical test(FIT) results. METHODS: The clinical outcomes of 194 UC patients in clinical remission who underwent colonoscopy were based on evaluations of Mayo endoscopic subscores(MESs) and FIT results.RESULTS: Patients with an MES of 0(n = 94, 48%) showed a ten-fold lower risk of relapse than those with an MES of 1-3(n = 100, 52%)(HR = 0.10, 95%CI: 0.05-0.19). A negative FIT result(fecal hemoglobin concentrations ≤ 100 ng/m L) was predictive of patients with an MES of 0, with a sensitivity of 0.94 and a specific of 0.76. Moreover, patients with a negative FIT score had a six-fold lower risk of clinical relapse than those with a positive score(HR = 0.17, 95%CI: 0.10-0.28). Inclusion of the distinguishing parameter, sustaining clinical remission 12 mo, resulted in an even stronger correlation between negative FIT results and an MES of 0 with respect to the risk of clinical relapse(HR = 0.11, 95%CI: 0.04-0.23).CONCLUSION: Negative FIT results one year or more after remission induction correlate with complete mucosal healing(MES 0) and better prognosis. Performing FIT one year after remission induction may be useful for evaluating relapse risk.     

Conventional therapy for moderate to severe inflammatory bowel disease: A systematic literature review

BACKGROUND Despite the advent of biological drugs, conventional therapy continues to be used in moderate to severe inflammatory bowel disease(MS-IBD). This study hypothesized that as a standard of treatment and the primary alternative to biologics, conventional therapy should present robust effectiveness results in IBD outcomes.AIM To investigate the effectiveness of conventional therapy for MS-IBD.METHODS A systematic review with no time limit was conducted in July 2017 through the Cochrane Collaboration, MEDLINE, and LILACS databases. The inclusion criteria encompassed meta-analyses, systematic reviews, randomized clinical trials, observational and case-control studies concerning conventional therapy in adult patients with MS-IBD, including Crohn's disease(CD) and ulcerative colitis(UC). Corticosteroids(prednisone, hydrocortisone, budesonide, prednisolone,dexamethasone), 5-aminosalicylic acid(5-ASA) derivatives(mesalazine and sulfasalazine) and immunosuppressants [azathioprine(AZA), methotrexate(MTX), mycophenolate, cyclosporine, tacrolimus, 6-mercaptopurine(6-MP)] were considered conventional therapy. The exclusion criteria were sample size below50; narrative reviews; specific subpopulations(e.g., pregnant women,comorbidities); studies on postoperative IBD; and languages other than English,Spanish, French or Portuguese. The primary outcome measures were clinical remission(induction or maintenance), clinical response and mucosal healing. As secondary outcomes, fecal calprotectin, hospitalization, death, and surgeries were analyzed. The quality of the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation criteria.RESULTS The search strategy identified 1995 citations, of which 27 were considered eligible(7 meta-analyses, 20 individual studies). For induction of clinical remission, four meta-analyses were selected(AZA and 6-MP showed no advantage over placebo,MTX or 5-ASA in CD; MTX showed no statistically significant difference versus placebo, 6-MP, or 5-ASA in UC; tacrolimus was superior to placebo for UC in two meta-analyses). Only one meta-analysis evaluated clinical remission maintenance, showing no statistically significant difference between MTX and placebo, 5-ASA, or 6-MP in UC. AZA and 6-MP had no advantage over placebo in induction of clinical response in CD. Three meta-analyses showed the superiority of tacrolimus vs placebo for induction of clinical response in UC. The clinical response rates for cyclosporine were 41.7% in randomized controlled trials(RCTs) and 55.4% in non-RCTs for UC. For induction of mucosal healing,one meta-analysis showed a favorable rate with tacrolimus versus placebo for UC. For secondary outcomes, no meta-analyses specifically evaluated fecal calprotectin, hospitalization or death. Two meta-analyses were retrieved evaluating colectomy rates for tacrolimus and cyclosporine in UC. Most of the twenty individual studies retrieved contained a low or very low quality of evidence.CONCLUSION High-quality evidence assessing conventional therapy in MS-IBD treatment is scarce, especially for remission maintenance, mucosal healing and fecal calprotectin.     

Meta-analysis: efficacy and safety of combination therapy of infliximab and immunosuppressives for Crohn's disease

Although infliximab and immunosuppressives have both proved to be effective in the treatment of Crohn's disease (CD), the efficacy and safety of the combination therapy remained undetermined yet. We performed a meta-analysis to evaluate the efficacy and safety of combination therapy of infliximab and immunosuppressives compared with monotherapy for maintaining steroid-free clinical remission on patients with CD. We searched PubMed, Cochrane Library, and EMBASE. The primary end point was steroid-free clinical remission after induction infusion and in short-term and long-term follow-ups. Total adverse events, severe adverse event, infection, severe infection, infusion reaction, sepsis, tuberculosis, and malignancy also were analyzed. Meta-analysis was carried out by combining the odds ratio (OR) between the combination therapy and monotherapy of the individual studies in a global OR, with statistical heterogeneity tested using the χ2-test and the I2-test. Five studies with eight comparisons involving 1026 patients were included. In an overall analysis, combination therapy was more effective than monotherapy for induction of remission at weeks 10-12 [mean OR=2.50; 95% confidence interval (CI)=1.46-4.30; P=0.0009)] and maintenance of remission at weeks 24-26 (mean OR=2.32; 95% CI=1.75-3.08; P<0.00001) and weeks 48-54 (mean OR=1.83; 95% CI=1.44-2.32; P<0.00001). In all five studies, combination therapy did not increase the risk of total adverse event, severe adverse event, infection, severe infection, and infusion reaction. The combination therapy of infliximab and immunosuppressives was more effective than monotherapy in the induction and maintenance remission of CD, and adverse events did not increase. However, larger clinical trials with longer follow-up are warranted to further assess the efficacy and safety profile of combination therapy.     

Meta-analysis of the effectiveness and safety of vedolizumab for ulcerative colitis

AIM: To conduct a meta-analysis examining the effectiveness and safety of vedolizumab for the treatment of ulcerative colitis (UC).METHODS: A search was conducted of MEDLINE, Cochrane, EMBASE, and Google Scholar on July 31, 2013. Inclusion criteria were: (1) Randomized controlled trial (RCT); (2) Patients treated for UC; and (3) Intervention was vedolizumab. The following information/data were extracted from studies that met the inclusion criteria: the name of the first author, year of publication, study design, patient demographic information, response rate, remission rate, and adverse events. The primary outcome was clinical response rate, and the secondary outcomes were clinical remission rate and serious adverse events. Odds ratio (OR) with 95%CI were calculated for each outcome.RESULTS: Of 224 studies initially identified, three RCTs examining the use of vedolizumab meeting the inclusion criteria were included in the meta-analysis. All studies examined the use of vedolizumab at dosages ranging from 0.5 to 10 mg/kg body weight (one study used a standard dose of 300 mg). The follow-up periods were approximately 6 wk. The total number of patients in the intervention groups was 901, and in the control groups was 221. The mean age of the patients was approximately 41 years, and approximately half were males. The follow-up periods ranged from 43 d to 6 wk. The clinical response and remission rates were significantly higher for patients who received vedolizumab as compared to control patients (clinical response: OR = 2.69; 95%CI: 1.94-3.74, P < 0.001 and remission rate: OR = 2.72; 95%CI: 1.76-4.19, P < 0.001). Serious adverse events were not higher in patients that received vedolizumab.CONCLUSION: This analysis supports the use of vedolizumab for the treatment of UC.     

Integrin antagonists are effective and safe for Crohn’s disease: A meta-analysis

AIM: To evaluate the efficacy and safety of integrin antagonists, including natalizumab and vedolizumab, in Crohn’s disease (CD).METHODS: We carried out a literature search in PubMed, MEDLINE, EMBASE and the Cochrane Library to screen for citations from January 1990 to August 2014. Data analysis was performed using Review Manager version 5.2.RESULTS: A total of 1340 patients from five studies were involved in this meta-analysis. During 6-12 wk treatment, integrin antagonists increased the rate of clinical response and remission with OR = 1.69, 95%CI: 1.37-2.09 and 1.84, 95%CI: 1.44-2.34, respectively. No significant difference was found between integrin antagonists and placebo treatments regarding their adverse reactions (OR = 1.07, 95%CI: 0.83-1.38) and serious adverse reactions (OR = 0.81, 95%CI: 0.57-1.15).CONCLUSION: The results prove the efficacy and safety of integrin antagonists for CD treatment, although the treatment strategies varied.     

A meta-analysis of the placebo rates of remission and response in clinical trials of active ulcerative colitis

BACKGROUND & AIMS: Knowledge of the placebo outcomes and understanding specific study features that influence these outcomes is important for designing future clinical trials evaluating therapy of ulcerative colitis (UC). The aims of this study were to estimate the placebo rates of remission and response in placebo-controlled, randomized clinical trials for active UC and to identify factors influencing these rates. METHODS: We performed a systematic review and meta-analysis of placebo-controlled, randomized clinical trials evaluating therapies for active UC identified from MEDLINE from 1966 through 2005. RESULTS: Forty studies met the inclusion criteria. The pooled estimates of the placebo rates of remission and response were 13% (95% confidence interval, 9%-18%; range, 0%-40%; median, 12%) and 28% (95% confidence interval, 23%-33%; range, 0%-67%; median, 30%), respectively, both with significant heterogeneity. Studies that used more stringent definitions of outcomes had lower placebo rates of remission and response. Study duration, number of study visits, disease duration, baseline composite and rectal bleeding scores of the disease activity index, and inclusion of endoscopic mucosal healing as the remission definition all were associated with the placebo remission rate. CONCLUSIONS: Rates of remission in the placebo arm of UC clinical trials ranges from 0% to 40%. The placebo remission rates are influenced by the trial length, number of study visits, use of stricter remission definitions, and design features that enroll patients with more active disease. These factors should be considered when designing future placebo-controlled clinical trials in patients with active UC.     

Safety of biologics in inflammatory bowel disease

Opinion statement Various biologic agents have been evaluated in patients with inflammatory bowel disease (eg, Crohn’s disease [CD]) and ulcerative colitis (UC). At present, only one, infliximab (humanized monoclonal anti-tumor necrosis factor-á antibody), is approved by the US Food and Drug Administration for induction and maintenance treatment in patients with active moderate to severe and/or fistulizing CD who are refractory to conventional therapy. Two recent trials, Active Ulcerative Colitis Trial (ACT) 1 and ACT 2, observed high efficacy of infliximab in inducting and maintaining clinical remission, mucosal healing, and corticosteroid-sparing effects in patients with moderate to severe UC. A plethora of randomized, double-blind, controlled and open-label, uncontrolled studies on large and small numbers of patients has assessed efficacy and safety of various biologic agents of potential use in treatment of inflammatory bowel disease. With respect to safety of biologic agents used for treatment, the most accurate data are available only in the case of infliximab. This is due to the fact that infliximab was evaluated in many more trials than any other biologic agent. Moreover, postmarketing experience also provides very valuable information about any side effects occurring during treatment with this agent.     

Safety of biologic therapy

Several biologic agents have been assessed in patients with inflammatory bowel disease (IBD; Crohn's disease [CD] and ulcerative colitis [UC]). Until recently, only infliximab (humanized monoclonal anti-TNF-alpha antibody) had been approved by the Food and Drug Administration (FDA) to induce and maintain remission in patients with active mild to moderate and/or fistulizing Crohn's disease who are refractory to conventional therapy. Two recent trials, ACT 1 and ACT2, observed high efficacy of infliximab in inducing and maintaining clinical remission, mucosal healing, and corticosteroid-sparing effects in patients with moderate to severe UC. This agent also was recently approved by the FDA for the treatment of ulcerative colitis to reduce signs and symptoms, to induce clinical remission and healing of the intestinal mucosa, and to eliminate the use of corticosteroids in patients with moderately to severely active UC who have had an inadequate response to conventional therapy. There have been many randomized, double-blind, controlled and open-label uncontrolled studies of large and small numbers of patients assessing the efficacy and safety of various biologic agents considered potentially useful in the treatment of IBD. Among all the biologic agents, infliximab has the most robust data on safety. This is because it has been evaluated in many more trials than has any other biologic agent. In addition, postmarketing experience provides very valuable information about adverse events occurring during treatment with this agent.     

布地奈德治疗胶原性结肠炎疗效和安全性的荟萃分析

背景:胶原性结肠炎以慢性水样腹泻和结肠黏膜上皮下胶原带增厚为特征,目前尚无标准治疗方案。目的:系统评价口服布地奈德治疗胶原性结肠炎的疗效和安全性。方法:计算机检索Cochrane Central Register of Controlled Trials(1995～2008.1)、MEDLINE/PubMed(1978～2009.12)、Ovid(1978～2009.12)、EMBASE(1978～2009.12)、中国期刊全文数据库(1980～2009.12)和万方数据资源系统(1980～2009.12),纳入所有口服布地奈德治疗胶原性结肠炎的随机对照试验(RCT),按Cochrane协作网推荐的方法进行荟萃分析。结果:共纳入5项RCT,包括179例患者,3项研究评价了诱导缓解治疗,2项评价了维持治疗。在诱导缓解方面,布地奈德的临床和组织学缓解率均优于安慰剂(OR=15.04,95% CI:5.47～41.33,P0.000 01;OR=34.02,95% CI:5.90～196.20,P0.0001)。在维持治疗方面,布地奈德的临床复发率和组织学缓解维持率亦优于安慰剂(OR=0.11.95% CI:0.04～0.31,P0.0001;0R=5.88,95% CI:1.90～18.17,P=-0.002)。布地奈德不良反应轻微,耐受性良好。结论:口服布地奈德能有效诱导并维持胶原性结肠炎的临床和组织学缓解,耐受性良好。由于本荟萃分析纳入研究的样本量较小,故应谨慎对待上述结论,并设计、开展大样本、高质量的RCT作进一步验证。     

微生态制剂对溃疡性结肠炎疗效的系统评价

背景：溃疡性结肠炎（UC）是一种病因尚未明确的慢性非特异性肠道炎症,微生态制剂在UC的治疗中起重要作用。目的：对微生态制剂联合标准方案（氨基水杨酸类制剂或糖皮质激素）治疗UC的疗效进行系统评价。方法：计算机检索Cochrane图书馆（截至2011．8）、MEDLINE（1966．11～2011．8）、EMBASE（1975．10－2011．8）、中国生物医学文献光盘数据库（1979．11-2011．8）和中文期刊全文数据库（1985．4－2011．8）等数据库．纳入微生态制剂组（微生态制剂联合标准方案）与对照组（标准方案联合安慰剂或空白对照）治疗UC的随机对照试验（RCT）,采用RevMan4．2软件行系统分析。结果：共纳入8项RCT,包括533例患者。微生态制剂组的UC临床缓解率和总有效率明显优于对照组,OR分别为2．48（95％CI：1．54－4．00）和7．38（95％CI：1．65～33．06）,临床有效率无明显差异（OR=2．64．95％CI：0．46～5．88）,而复发率明显低于对照组（OR=0．22,95％CI：0．05。0．87）。结论：微生态制剂联合标准方案对诱导和维持UC缓解的疗效优于单用标准方案．     

益生菌制剂VSL#3对溃疡性结肠炎诱导缓解作用的系统评价

循证医学证据提示益生菌对溃疡性结肠炎（UC）的诱导缓解无效,但对维持缓解有效,然而2009年发表的两项临床试验结果显示益生菌合剂VSL#3对UC的诱导缓解有效。目的：系统评价益生菌尤其是VSL#3诱导UC缓解的有效性和安全性。方法：联机检索MEDLINE、EMBASE、CochraneLibrary和中国生物医学文献数据、万方数据库,由两名分析人员独立选取与UC诱导缓解相关、比较益生菌治疗组与对照组（安慰剂或阳性对照）的随机对照试验（不限语种）并提取数据。应用RevMan5．2．10软件行meta分析,同时行亚组分析和敏感性分析。结果：共纳入9项随机对照试验,共557例UC患者,其中4项治疗组使用VSL#3。Meta分析显示益生菌组总体诱导缓解率显著优于对照组（OR=2．05,95％CI：1．14～3．70,P=0．02）,亚组分析显示VSL#3亚组诱导缓解率显著优于对照组（OR：2．35,95％CI：1．45—3．80,P=0．0005）,其他菌种与对照组间诱导缓解率无明显差异。益生菌组、VSL#3亚组与对照组间不良反应发生率均无明显差异。敏感性分析显示meta分析结果稳定。结论：VSL#3对UC的诱导缓解作用优于对照组且安全性高。     

Meta-Analysis of the Placebo Response in Ulcerative Colitis

Purpose The placebo response rate in randomized controlled trials (RCTs) in ulcerative colitis (UC) varies from 0 to 76%. The aims of this study were to quantify the pooled placebo response rate and identify the factors affecting it. Methods We performed a meta-analysis of 110 RCTs carried out between 1955 and 2005 and published in English. Regression analysis was used to identify factors significantly modifying placebo response. Results The pooled placebo remission rate was 23% (95%CI: 18.4–28%) and the pooled placebo improvement rate was 32.1% (95%CI: 28.1–36.3%). Multivariate analysis showed that the country where the study was performed (P = 0.025 for placebo remission and P = 0.0083 for placebo response rates) significantly influenced the placebo remission and response rates. Conclusion Placebo remission and response rates in RCTs of UC are highly variable and are significantly influenced by the country in which the RCT is performed.     

Frequency and prognostic role of mucosal healing in patients with Crohn’s disease and ulcerative colitis after one-year of biological therapy

AIM:To assess the endoscopic activity before and after a one-year period of biological therapy and to evaluate the frequency of relapses and need for retreatment after stopping the biologicals in patients with Crohn’s disease(CD)and ulcerative colitis(UC).METHODS:The data from 41 patients with CD and 22 patients with UC were assessed.Twenty-four CD patients received infliximab,and 17 received adalimumab.The endoscopic severity of CD was quantified with the simplified endoscopic activity score for Crohn’s disease in CD and with the Mayo endoscopic subscore in UC.RESULTS:Mucosal healing was achieved in 23 CD and7 UC patients.Biological therapy had to be restarted in78%of patients achieving complete mucosal healing with CD and in 100%of patients with UC.Neither clinical remission nor mucosal healing was associated with the time to restarting the biological therapy in either CD or UC.CONCLUSION:Mucosal healing did not predict sustained clinical remission in patients in whom the biological therapies had been stopped.     

How effective are current drugs for Crohn's disease? A meta-analysis.

We have conducted a meta-analysis of 12 placebo controlled trials to determine the efficacy of single drug therapy in Crohn's disease for both induction (seven trials) and maintenance (five trials) of remission. A total of 767 and 796 patients were studied, respectively. Various clinical criteria of success were analyzed. The Dersimonian-Laird method for meta-analysis was used to calculate the risk difference (RD). Therapeutic advantage, defined as the difference between drug and placebo response, was also determined. Using various criteria of success, we found that single drug therapy conferred an 11-29% therapeutic advantage (RD = 0.13-0.33) over placebo for the induction of remission. In trials for maintenance, no therapeutic advantage was found for single drug therapy over placebo. All forms of maintenance therapy followed nearly identical linear rates of relapse over time, showing an approximately 90% maintenance of remission rate at 3 months, which decreased to 25% at 36 months. In conclusion, meta-analysis has established a standard of reference against which future drug trials can be compared. This standard of reference for drug and placebo rates, as well as the corresponding risk differences and therapeutic advantages can help determine the relative value of newer agents in the therapy of Crohn's disease.     

An updated systematic review and meta-analysis of fecal microbiota transplantation for the treatment of ulcerative colitis

Background:Fecal microbiota transplantation (FMT) as a promising therapy for ulcerative colitis (UC) remains controversial. We conducted a systematic review and meta-analysis to assess the efficiency and safety of FMT as a treatment for UC.Methods:The target studies were identified by searching PubMed, EMBASE, the Cochrane Library, Web of Science, and ClinicalTrials and by manual supplementary retrieval. We conducted a general review and quantitative synthesis of included studies. We used the RevMan and Stata programs in the meta-analysis. The outcomes were total remission, clinical remission, steroid-free remission, and serious adverse events. We also performed subgroup analyses based on different populations.Results:A total of 34 articles were included in the general review. Only 16 articles, including 4 randomized controlled trials, 2 controlled clinical trials, and 10 cohort studies, were selected for the meta-analysis. We found that donor FMT might be more effective than placebo for attaining total remission (risk ratio [RR]: 2.77, 95% confidence interval [CI]: 1.54–4.98; P = .0007), clinical remission (RR: 0.33, 95% CI: 0.24–0.41; P < .05), and steroid-free remission (RR: 3.63, 95% CI: 1.57–8.42; P = .003), but found no statistically significant difference in the incidence of serious adverse events (RR: 0.88, 95% CI: 0.34–2.31, P = .8). The subgroup analyses revealed significant differences between the pooled clinical remission rates for different regions, degrees of severity of the disease, and patients with steroid- or nonsteroid-dependent UC.Conclusions:FMT can achieve clinical remission and clinical response in patients with UC.     

Efficacy and Safety of Adalimumab in Moderately to Severely Active Cases of Ulcerative Colitis: A Meta-Analysis of Published Placebo-Controlled Trials

Background/Aims

To evaluate the efficacy and safety of adalimumab (ADA) in moderately to severely active ulcerative colitis (UC) patients who are unresponsive to traditional therapy.

Methods

Electronic databases, including the PubMed, Embase, and Cochrane databases, were searched to April 20, 2014. UC-related randomized controlled trials (RCTs) that compared ADA with placebo were eligible. Review Manager 5.1 was used for data analysis.

Results

This meta-analysis included three RCTs. ADA was considerably more effective compared with a placebo, and it increased the ratio of patients with clinical remission, clinical responses, mucosal healing and inflammatory bowel disease questionnaire responses in the induction and maintenance phases (p<0.05), as well as patients with steroid-free remission (p<0.05) during the maintenance phase. Clinical remission was achieved in a greater number of UC cases in the ADA 160/80/40 mg groups (0/2/4 week, every other week) compared with the placebo group at week 8 (p=0.006) and week 52 (p=0.0002), whereas the week 8 clinical remission rate was equivalent between the ADA 80/40 mg groups and the placebo group. Among the patients who received immunomodulators (IMM) at baseline, ADA was superior to the placebo in terms of inducing clinical remission (p=0.01). Between-group differences were not observed in terms of serious adverse events (p=0.61).

Conclusions

ADA, particularly at doses of 160/80/40 mg (0/2/4 week, every other week), is effective and safe in patients with moderate-to-severe UC who are unresponsive to traditional treatment. Concomitant IMM therapy may improve the short-term therapeutic efficacy of ADA.     

Endoscopic submucosal dissection vs endoscopic mucosal resection for colorectal tumors: A meta-analysis

AIM: To compare the efficacy and safety of endoscopic submucosal dissection (ESD) and endoscopic mucosal resection (EMR) for the treatment of colorectal tumors.METHODS: Databases, such as PubMed, EMBASE, Cochrane Library and Science Citation Index updated to 2013 were searched to include eligible articles. In the meta-analysis, the main outcome measurements were the en bloc resection rate, the histological resection rate and the local recurrence rate. Meanwhile, we also compared the operation time and the incidence of procedure-related complications.RESULTS: Six trials were identified and a total of 1642 lesions were included. The en bloc resection rate was higher and the local recurrence rate was lower in the ESD group compared with the EMR group (OR = 7.94; 95%CI: 3.96-15.91; OR = 0.09; 95%CI: 0.04-0.19). There was no significant difference in histological resection rate(OR = 1.65; 95%CI: 0.29-9.30) and procedure-related complication rate between the two groups (OR = 1.59; 95%CI: 0.92-2.73). The meta-analysis also showed that ESD was more time consuming than EMR.CONCLUSION: Compared with EMR, ESD results in higher en bloc resection rate and lower local recurrence rate for the treatment of colorectal tumors, without increasing the procedure-related complications.