Seow Cynthia H, Benchimol Eric I, Griffiths Anne Marie, Steinhart A Hillary
Mount Sinai Hospital, Room 445, 600 University Ave, Toronto, Ontario, Canada, M5G 1X5.
Cochrane Database Syst Rev. 2008 Jul 16(3):CD006790. doi: 10.1002/14651858.CD006790.pub2.
Interferons (IFNs) are cytokines which possess immunoregulatory properties and have been used to successfully treat a number of chronic inflammatory disorders. It has been postulated that Type I IFNs may be able to re-establish the Th1/Th2 balance in Th2 predominant diseases like ulcerative colitis.
To systematically evaluate the efficacy and safety of type I IFN therapy for induction of remission in ulcerative colitis.
The following electronic databases were searched: MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, the Cochrane Inflammatory Bowel Disease and Functional Bowel Disorders (IBD/FBD) Group Specialised Trial Register, and http://ClinicalTrials.gov. Reference lists of trials and review articles, as well as recent proceedings from major gastroenterology meetings were manually searched. Contact was made with pharmaceutical companies manufacturing type I IFNs.
Randomised controlled trials of type I IFNs for induction of remission in UC were included. The study population included patients of any age with active ulcerative colitis. There were no exclusions based on type, dose or duration of IFN treatment. The primary outcome was induction of remission of ulcerative colitis. Secondary outcomes included: time to remission, mean change in disease activity index score, clinical, histological or endoscopic improvement, improvement in quality of life, and adverse events.
Two independent investigators reviewed studies for eligibility, extracted the data and assessed study quality using Jadad's criteria. A random or fixed effects model was chosen based on an assessment of heterogeneity, and studies were weighted using the DerSimonian & Laird or the Mantel-Haenszel method accordingly. Meta-analysis was performed using RevMan 4.2.10 software.
Four studies were eligible for inclusion. Three studies compared type I IFNs to placebo and a single study compared IFNs to prednisolone enemas in patients with left-sided colitis. Meta-analysis was based on the three IFN-placebo studies. There was no significant benefit of type I IFNs over placebo for inducing remission in ulcerative colitis (RR 1.24; 95% CI 0.81 to 1.90). There were no statistically significant differences in any of the secondary outcome variables.
AUTHORS' CONCLUSIONS: The existing literature does not support the efficacy of type I IFNs for induction of remission in patients with UC. Given concerns regarding the tolerability of IFN therapy, we suggest that the results of two ongoing trials are evaluated for efficacy and safety prior to development or commencement of further randomised controlled trials of type I IFNs in UC.
干扰素（IFNs）是具有免疫调节特性的细胞因子，已被成功用于治疗多种慢性炎症性疾病。据推测，I型干扰素可能能够在以Th2为主的疾病如溃疡性结肠炎中重建Th1/Th2平衡。
系统评价I型干扰素治疗溃疡性结肠炎诱导缓解的疗效和安全性。
检索了以下电子数据库：MEDLINE、EMBASE、Cochrane对照试验中心注册库、Cochrane炎症性肠病和功能性肠病（IBD/FBD）小组专门试验注册库以及http://ClinicalTrials.gov。人工检索了试验和综述文章的参考文献列表以及主要胃肠病学会议的近期会议记录。与生产I型干扰素的制药公司进行了联系。
纳入I型干扰素诱导溃疡性结肠炎缓解的随机对照试验。研究人群包括任何年龄的活动性溃疡性结肠炎患者。不根据干扰素治疗的类型、剂量或持续时间进行排除。主要结局是溃疡性结肠炎的缓解诱导。次要结局包括：缓解时间、疾病活动指数评分的平均变化、临床、组织学或内镜改善、生活质量改善以及不良事件。
两名独立研究者审查研究的合格性，提取数据并使用Jadad标准评估研究质量。根据异质性评估选择随机或固定效应模型，并相应地使用DerSimonian & Laird法或Mantel-Haenszel法对研究进行加权。使用RevMan 4.2.10软件进行荟萃分析。
四项研究符合纳入标准。三项研究将I型干扰素与安慰剂进行比较，一项研究将干扰素与左侧结肠炎患者的泼尼松龙灌肠剂进行比较。荟萃分析基于三项干扰素-安慰剂研究。I型干扰素在诱导溃疡性结肠炎缓解方面并不比安慰剂有显著优势（RR 1.24；95%CI 0.81至1.90）。在任何次要结局变量中均无统计学显著差异。
现有文献不支持I型干扰素对溃疡性结肠炎患者诱导缓解的疗效。鉴于对干扰素治疗耐受性的担忧，我们建议在开展或启动I型干扰素治疗溃疡性结肠炎的进一步随机对照试验之前，评估两项正在进行的试验的疗效和安全性。
