干扰素-β治疗复发-缓解型多发性硬化系统评价  

Interferon-beta for relapsing-remitting multiple sclerosis:a systematic review

作　　者：贺电[1] 李娅[1] 徐竹[1] 周红雨[2] 楚兰[1] 蔡刚[1] 戴庆箐 张艺凡[1] 

机构地区：[1]贵阳医学院附属医院神经内科,550004 [2]四川大学华西医院神经内科,成都610041

出　　处：《中国现代神经疾病杂志》2014年第9期775-788,共14页Chinese Journal of Contemporary Neurology and Neurosurgery

基　　金：贵州省科技计划项目(项目编号:黔科合LG字[2011]044号)~~

摘　　要：目的评价干扰素-β（IFN-β）治疗复发．缓解型多发性硬化的有效性和安全性。方法 检索Cochrane临床对照试验中心注册库、美国国立医学图书馆、荷兰医学文摘、CINAHL、LILACS、PEDRO、中国生物医学文献数据库、临床试验注册中心和世界卫生组织国际临床试验注册平台（检索截止时间2014年6月）；并通过阅读相关论文参考文献，联系参与IFN-β治疗多发性硬化临床试验的研究者和企业，进一步获取研究信息或未发表的数据。由两名评价人员独立筛选研究、提取研究信息和数据、评价偏倚风险。应用Review Manager软件（Version 5．3．3）进行Meta分析，GRADEpro软件评价研究设计和实施过程中的局限性（偏倚风险）、结果的不一致性和不精确性、证据的间接性和发表偏倚对主体证据质量的影响。结果共检索相关文献576篇，阅读标题和摘要后初步筛选出26项研究；进一步阅读全文后纳入5项研究（共2129例复发一缓解型多发性硬化患者：高剂量IFN-β组1076例、安慰剂组1053例）。所有纳入的研究均为IFN-β单药治疗且随访时间≥1年的随机双盲安慰剂对照平行临床试验。大多数研究存在方法学局限性，主要缺陷为随访偏倚风险较高，且数据分析未使用意向治疗原则，仅919例受试者（43．17％）的数据可用于分析随访2年时的主要结局。Meta分析显示，IFN-β轻微减少随访2年时复发病例数（RR：0．810，95％CI：0．740～0．890；P=0．000）和残疾进展病例数（RR=0．700，95％CI：0．550～0，880；P=O．002）；敏感性分析（最差情况的演示分析）显示，IFN-β治疗无效（RR=1．110，95％CI：O．730～1．680，P=0．620；RR=1．310，95％CI：0．600～2．890，P=0．500）。共1581例患者（74．26％）的数据可用于分析随访1年时至少复发1次的病例数（RR=O．740，95％CI：0．590～0．930；P=0．010），绝对危险�Objective To assess the efficacy and safety of interferon-beta(IFN-β) as monotherapyversus placebo for patients with relapsing-remitting multiple sclerosis(RRMS).Methods We searched Cochrane Central Register of Controlled Trials(CENTRAL), PubMed, EMBASE, CINAHL, LILACS,PEDRO, China Biology Medicine Disc(CBMDisc), as well as clinical trial registries and the World HealthOrganization International Clinical Trials Registry Platform(WHO ICTRP, retrieval deadline: June 2014).Furthermore, we checked reference lists of published reviews and retrieved articles, and communicatedpersonally with investigators and biotechnology companies participating in trials of IFN-β in an effort toidentify further studies or unpublished data. Two review authors independently screened studies, extracteddata and evaluated the risk of bias. Formal Meta-analysis were conducted by using Review Managersoftware(Version 5.3.3) and the impacts of limitations in study design or execution(risk of bias),inconsistency in results, imprecision of results, indirectness of evidence and publication bias on the qualityof the body of evidence were assessed.Results A total of 576 articles were retrieved. After screening oftitles and abstracts, 26 studies were provisionally selected. The full text of papers were obtained for furtherassessment of eligibility. Finally, 5 studies were included, involving 2129 patients with RRMS(high-doseIFN-β group: N= 1076; placebo group: N= 1053). All studies were randomized, double-blind, controlled,parallel-group clinical trials with a follow-up for at least one year, evaluating IFN-β versus placebo asmonotherapy for patients with RRMS. Most studies had methodological limitations, mainly on a high risk ofattrition bias. Moreover, the intention to treat(ITT) principle was not used in data analysis. Data from only919 patients(43.17%) were available to calculate the primary outcomes at 2 years of follow-up. Meta-analysis indicated IFN-β slightly reduced the number of patients with at least one relapse [risk ratio(RR)=0.810

关 键 词：干扰素Β 多发性硬化 META分析 

分 类 号：R744.51[医药卫生—神经病学与精神病学]