奥马珠单抗治疗难治性过敏性哮喘疗效和安全性的荟萃分析

Efficacy and safety of omalizumab in patients with refractory allergic asthma:a meta‑analysis

目的分析探讨奥马珠单抗对难治性过敏性哮喘患者的治疗效果及安全性。方法以anti‑IgE、anti‑immunoglobulin E、anti‑IgE antibody、omalizumab、rhuMAb‑E25、Xolair和allergic asthma为关键词,检索PubMed、Web of Science、Embase数据库以及Clinicaltrials.gov注册网站截至2020年9月19日发表的与奥马珠单抗治疗难治性哮喘有关的随机对照研究。采用Review Manager 5.4软件和Stata16软件进行数据分析,计算合并的RR或加权均数差(WMD)及其95%CI,检验异质性,评估发表偏倚。结果共纳入15项随机对照试验的6316例患者,其中奥马珠单抗组3469例,安慰剂组2847例。在药物疗效方面,与安慰剂对比,奥马珠单抗在吸入性糖皮质激素(ICS)恒定期(RR=0.69,95%CI:0.63~0.75,P<0.001;I2=39.0%,P=0.090)和吸入性糖皮质激素减量期(RR=0.55,95%CI:0.46~0.66,P<0.001;I2=41.0%,P=0.180)均能降低哮喘患者急性发作风险,减少急诊就诊率(RR=0.53,95%CI:0.38~0.73,P<0.001;I2=0,P=0.420),减少患者ICS用量(RR=1.35,95%CI:1.25~1.45,P<0.001;I2=22.0%,P=0.280)甚至完全停用(RR=1.80,95%CI:1.41~2.31,P<0.001;I2=57.0%,P=0.070),明显改善哮喘生活质量问卷(AQLQ)评分(RR=1.81,95%CI:1.51~2.17),缓解药物使用的例数减少(RR=0.78,95%CI:0.67~0.92),但是缓解药物的用量(喷/d)差异无统计学意义(WMD=-0.32,95%CI:-0.77~0.13)。在药物安全性方面,与安慰剂组相比,奥马珠单抗组总的不良事件(RR=1.01,95%CI:0.98~1.03)和严重不良事件(RR=0.89,95%CI:0.74~1.06)的发生率差异均无统计学意义。结论奥马珠单抗对于难治性过敏性哮喘是一种理想的附加治疗,疗效佳且安全性高,但关于其合适的疗程尚需进一步的随机对照试验。

Objective To evaluate the efficacy and safety of omalizumab in patients with refractory allergic asthma using meta‑analysis.Methods We searched databases including PubMed,Web of Science,Embase and the website of ClinicalTrials.gov registry for randomized controlled trials(RCTs),using the search terms:("anti‑IgE"OR"anti‑immunoglobulin E"OR"anti‑IgE antibody"OR"omalizumab"OR"rhuMAb‑E25"OR"Xolair")AND("allergic asthma").The time was up to September 19th 2020.Review Manager 5.4 software and Stata16 software were used to calculate pooled RR or WMD,perform heterogeneity test,and assess publication bias.Results Fifteen RCTs with 6316 patients in total(omalizumab,n=3469;placebo,n=2847)met our selection criteria.Comparing with placebo,omalizumab reduced the risk of asthma exacerbations during both stable‑inhaled corticosteroid(ICS)phase(RR=0.69,95%CI:0.63-0.75,P<0.001;I2=39.0%,P=0.090)and ICS‑reduction phase(RR=0.55,95%CI:0.46-0.66,P<0.001;I2=41.0%,P=0.180),reduced emergency visits(RR=0.53,95%CI:0.38-0.73,P<0.001;I2=0,P=0.420),made a significant reduction in dosage of ICS(RR=1.35,95%CI:1.25-1.45,P<0.001;I2=22.0%,P=0.280)and even withdrew from ICS completely(RR=1.80,95%CI:1.41-2.31,P<0.001;I2=57.0%,P=0.070).Omalizumab significantly improved asthma‑related quality of life(RR=1.81,95%CI:1.51-2.17).The use of rescue bronchodilators was significantly reduced in the omalizumab group(RR=0.78,95%CI:0.67-0.92)but there was no significant difference in the dosage of rescue bronchodilators(puff per day)(WMD=-0.32,95%CI:-0.77-0.13).Patients taking omalizumab did not increase the frequency of any adverse events(RR=1.01,95%CI:0.98-1.03)and serious adverse events(RR=0.89,95%CI:0.74-1.06).Conclusions Omalizumab is an ideal adjunctive treatment for refractory allergic asthma with good efficacy and safety.Further randomized controlled trials are needed to determine the appropriate duration of treatment.