Walker S, Monteil M, Phelan K, Lasserson T J, Walters E H
National Respiratory Training Centre, The Athenaeum, 10 Church Street, Warwick, UK, CV34 4AB.
Cochrane Database Syst Rev. 2006 Apr 19(2):CD003559. doi: 10.1002/14651858.CD003559.pub3.
Omalizumab is a recombinant humanised monoclonal antibody directed against immunoglobulin E (anti-IgE) to inhibit the immune system's response to allergen exposure. Omalizumab is directed against the binding site of IgE for its high affinity Fc receptor. It prevents free serum IgE from attaching to mast cells and other effector cells and prevents IgE mediated inflammatory changes.
To determine the efficacy of anti-IgE compared with placebo in patients with allergic asthma
We searched the Cochrane Airways Group Asthma trials register for potentially relevant studies (February 2006).
Randomised controlled trials examining anti-IgE administered in any manner for any duration. Trials with co-interventions were included as long as they were the same in each arm.
Two reviewers independently assessed study quality and extracted and entered data. Three modes of administration were identified from the published literature (inhaled, intravenous and subcutaneous injection). Subgroup analysis was performed by asthma severity. Data were extracted from published and unpublished sources.
Fourteen trials (15 group comparisons) were included in the review, contributing a total of 3143 mild to severe allergic asthmatic participants with high levels of IgE. Treatment with intravenous and subcutaneous Omalizumab significantly reduced free IgE compared with placebo. Omalizumab led to a significant reduction in inhaled steroid (ICS) consumption compared with placebo (-119 mcg/day (95% CI -154 to -83, three trials)). There were significant increases in the number of participants who were able to reduce ICS by over 50% (odds ratio (OR) 2.50, 95% confidence interval (CI) 2.02 to 3.10 (four trials)); or completely withdraw their daily ICS intake (OR 2.50 (95%CI 2.00 to 3.13; four trials)). Participants treated with Omalizumab were less likely to suffer an asthma exacerbation with treatment as an adjunct to ICS (OR 0.52, 95%CI 0.41 to 0.65, five trials), or as an ICS tapering agent (OR 0.47, 95% CI 0.37 to 0.60, four trials).
AUTHORS' CONCLUSIONS: Omalizumab was significantly more effective than placebo at increasing the numbers of patients who were able to reduce or withdraw their inhaled steroids, but the clinical value of the reduction in steroid consumption has be considered in the light of the high cost of Omalizumab. The impressive placebo effects observed in control groups bring into question the true effect of Omalizumab. Omalizumab was effective in reducing asthma exacerbations as an adjunctive therapy to inhaled steroids, and during steroid tapering phases of clinical trials. Omalizumab was generally well tolerated, although there were more injection site reactions with Omalizumab. Patient and physician assessments of the drug were positive. Further assessment in paediatric populations is necessary, as is direct double-dummy comparison with ICS.
奥马珠单抗是一种重组人源化单克隆抗体，可靶向免疫球蛋白E（抗IgE），以抑制免疫系统对过敏原暴露的反应。奥马珠单抗针对IgE与其高亲和力Fc受体的结合位点。它可防止游离血清IgE附着于肥大细胞和其他效应细胞，并防止IgE介导的炎症变化。
确定抗IgE与安慰剂相比在过敏性哮喘患者中的疗效
我们检索了Cochrane Airways Group哮喘试验注册库，以查找潜在相关研究（2006年2月）。
以任何方式、在任何持续时间内使用抗IgE的随机对照试验。只要各治疗组的联合干预措施相同，就纳入有联合干预措施的试验。
两名评价员独立评估研究质量，并提取和录入数据。从已发表文献中确定了三种给药方式（吸入、静脉注射和皮下注射）。按哮喘严重程度进行亚组分析。数据从已发表和未发表的来源中提取。
本综述纳入了14项试验（15组比较），共纳入3143名轻度至重度过敏性哮喘患者，这些患者的IgE水平较高。与安慰剂相比，静脉注射和皮下注射奥马珠单抗可显著降低游离IgE水平。与安慰剂相比，奥马珠单抗可使吸入性糖皮质激素（ICS）的用量显著减少（-119微克/天（95%可信区间-154至-83，三项试验））。能够将ICS用量减少50%以上的参与者数量显著增加（比值比（OR）为2.50，95%可信区间（CI）为2.02至3.10（四项试验））；或完全停止每日ICS摄入量的参与者数量也显著增加（OR为2.50（95%CI为2.00至3.13；四项试验））。作为ICS辅助治疗时，接受奥马珠单抗治疗的参与者哮喘发作的可能性较小（OR为0.52，95%CI为0.41至0.65，五项试验）；或作为ICS减量药物时也是如此（OR为0.47，95%CI为0.37至0.60，四项试验）。
奥马珠单抗在增加能够减少或停用吸入性糖皮质激素的患者数量方面显著优于安慰剂，但鉴于奥马珠单抗成本高昂，需考虑减少糖皮质激素用量的临床价值。在对照组中观察到的显著安慰剂效应使人对奥马珠单抗的真实效果产生质疑。作为吸入性糖皮质激素的辅助治疗以及在临床试验的糖皮质激素减量阶段，奥马珠单抗在减少哮喘发作方面有效。奥马珠单抗一般耐受性良好，尽管其注射部位反应较多。患者和医生对该药物的评价为阳性。有必要在儿科人群中进行进一步评估，以及与ICS进行直接双盲对照比较。
