炎症性肠病患者行抗肿瘤坏死因子α治疗时潜伏性结核感染发病率的一项Meta分析

发布时间：2018-04-23 07:41

本文选题：炎症性肠疾病 + 克罗恩病　；参考：《东南大学》2016年硕士论文

【摘要】：背景：虽然抗肿瘤坏死因子-α治疗不是一线治疗方案,但是它具有维持病情缓解、促进粘膜愈合、改善生活质量等优势。目前已经用于临床治疗的抗肿瘤坏死因子-α制剂有英夫利昔单抗、阿达木单抗、赛妥珠单抗、戈利木单抗等。由于生物制剂治疗可显著抑制自身免疫系统,存在着增加肺结核复发或者进展的风险,也可引起其他严重的感染性疾病如病毒性肝炎、恶性肿瘤、皮肤病以及药物引起的系统性红斑狼疮样综合征和脱髓鞘疾病的风险。这项研究的目的在于对过去和近几年IBD患者在抗肿瘤坏死因子-α治疗前和治疗过程中潜伏性结核感染的发病率予进行调查并分析。方法：计算机检索Cochrane library, Pubmed, EMBASE和BMJBestPractice, Google scholar, Annals Gastroenterology, JCC journal等数据库中已发表的或未发表的抗肿瘤坏死因子a治疗炎症性肠病的所有英文文献,检索起止时间为2003-2015。检索关键词为与英夫力昔相关的词语‘"infliximab," immunogenicity," "human anti-chimeric antibodies (HACAs)," "ulcerative colitis," "Crohn's disease," "Tuberculosis; Latent Tuberculosis;" "Anti TNF-a agents"。并设定入组标准及排除标准,采用STATA12.0软件进行分析,我们设计了一个随机效应模型的Meta分析,来评估结果变量顺序的变化。通过随机效应模型对OR值和异质性进行分析,如果P0.05,则说明异质性是显著的,并绘制漏斗图评定有无发表偏倚。结果：我们检索了923篇引文和16篇包括完整的文章和摘要的文献用于Meta分析,对于选中的12篇文献中分析了抗TNF-α治疗中抗结核治疗患者与未抗结核治疗患者中新发结核感染和结核复发的风险,因存在异质性使用了固定效应模型(I2：47.6%)。合并估计95% CI=7.83(4.44,1 3.79),P=0.033显示对于存在结核潜伏感染阳性的患者予以预防性抗结核治疗后复发率降低的研究具有显著统计学意义,而且在抗TNFα治疗中潜伏结核感染测试阴性患者发展成为结核可能性较低。结核感染的发病率也许根据结核病流行区域的不同存在着差异,在抗TNF-α治疗前存在潜伏结核感染的研究中,我们从16篇文献中剔除了2个研究(因其不符合纳入标准中对于潜伏性结核感染的计算结果)。余14篇研究中均存在显著的潜伏性结核感染,整体综合评估95% Cl：0.14(0.11,0.18),P0.05,显示研究中的IBD患者在抗肿瘤坏死因子-α治疗前就存在着不同数目的潜伏性结核感染。在所有研究中结核感染(复发或新发)进行了测量,并通过随机效应模型进行异质性分析。在抗TNF-α治疗后出现潜伏性结核感染的研究中,16项研究分别显示结核复发率显著的减少,整体综合评估95% Cl：0.02 (0.01～0.02,P0.05说明研究结果存在显著的统计学意义。绘制漏斗图评定并通过进行Begg's和Egger's检验显示可能存在发表偏倚,对于不对称的漏斗图结果进行敏感性分析显示分析结果是稳定的。结论：尽管抗肿瘤坏死因子-α治疗非常有效,但是增加了潜伏性结核感染风险。在抗TNF-a治疗前,筛查潜伏性结核感染及预防性治疗可减少潜伏性结核转化为结核感染。所以,临床医生应该在使用生物制剂之前意识到治疗可能存在的风险。
[Abstract]:Background: Although antitumor necrosis factor - alpha therapy is not a first-line treatment, it has the advantages of maintaining the remission of the disease, promoting the healing of the mucous membrane and improving the quality of life. The antitumor necrosis factor - alpha preparation currently used for clinical treatment is infliximab, adadumumab, cetuzumab, and GL mAb, and so on. Preparations can significantly inhibit the autoimmune system, the risk of increasing the recurrence or progression of tuberculosis, and other serious infectious diseases such as viral hepatitis, malignant tumor, dermatosis and the risk of systemic lupus erythematosus syndrome and demyelinating disease caused by drugs. This study aims at the past. And in recent years, the incidence of latent tuberculosis infection in IBD patients before and during the treatment of TNF - alpha was investigated and analyzed. Methods: computer retrieval of Cochrane library, Pubmed, EMBASE and BMJBestPractice, Google scholar, Annals Gastroenterology, JCC journal and so on. All the English literature of the antitumor necrosis factor A for the treatment of inflammatory bowel disease, the retrieval time and stop time of 2003-2015. retrieval key words "infliximab," immunogenicity, "" human anti-chimeric antibodies (HACAs), "" ulcerative colitis, "" Crohn's disease, "" "Is;" "Anti TNF-a agents". And setting up group standards and exclusion criteria, using STATA12.0 software to analyze. We designed a Meta analysis of a random effect model to evaluate the change in the sequence of the result variables. By analyzing the OR value and heterogeneity through the random effect model, if P0.05, it shows that heterogeneity is significant and draws a leak. Results: We searched 923 quotations and 16 articles including complete articles and abstracts for Meta analysis. In the 12 selected articles, we analyzed the risk of new tuberculosis infection and tuberculosis relapse in anti tuberculosis treatment and non anti tuberculosis treatment patients in the 12 selected articles, because of heterogeneity. The fixed effect model (I2:47.6%) was used. The combined estimate of 95% CI=7.83 (4.44,1 3.79) was used, and P=0.033 showed significant statistical significance for the study of the decrease in the recurrence rate after the preventive anti tuberculosis treatment of the patients with positive tuberculosis infection, and the development of the negative patients with the latent tuberculosis infection in the anti TNF alpha therapy was developed into a knot. There is a low nuclear possibility. The incidence of tuberculosis infection may vary according to the difference in the epidemic area of tuberculosis. In the study of latent tuberculosis infection in the presence of TNF- alpha before treatment, we have removed 2 studies from 16 articles (because of the results of the latent tuberculosis infection in the incompatible inclusion criteria). The remaining 14 studies are all deposited. In the significant latent tuberculosis infection, the overall comprehensive assessment of 95% Cl:0.14 (0.11,0.18), P0.05, showed that the IBD patients in the study had different number of latent tuberculosis infection before the TNF - alpha therapy. Sex analysis. In the study of latent tuberculosis infection after anti TNF- alpha therapy, 16 studies showed a significant reduction in the recurrence rate of tuberculosis and a comprehensive comprehensive assessment of 95% Cl:0.02 (0.01 to 0.02, P0.05 showed significant statistical significance.) the funnel map was assessed and the Begg's and Egger's tests showed possible survival. Sensitivity analysis of asymmetric funnel map results showed that the results were stable in the publication bias. Conclusion: Although anti TNF - alpha therapy is very effective, it increases the risk of latent tuberculosis infection. Screening latent tuberculosis infection and preventive treatment can reduce latent tuberculosis transformation before anti TNF-a treatment. For TB infection, clinicians should be aware of possible risks before using biologics.

【学位授予单位】：东南大学
【学位级别】：硕士
【学位授予年份】：2016
【分类号】：R574

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