Division of Allergy and Immunology, University of South Florida, Tampa, FL, USA.
Capital Allergy & Respiratory Disease Center, Sacramento, CA, USA.
Allergy. 2018 Feb;73(2):490-497. doi: 10.1111/all.13302. Epub 2017 Sep 23.
Recent efficacy studies of asthma biologics have included highly enriched patient populations. Using a similar approach, we examined factors that predict response to omalizumab to facilitate selection of patients most likely to derive the greatest clinical benefit from therapy.
Data from two phase III clinical trials of omalizumab in patients with allergic asthma were examined. Differences in rates of asthma exacerbations between omalizumab and placebo groups during the 16-week inhaled corticosteroid (ICS) dose-stable phase were evaluated with respect to baseline blood eosinophil counts (eosinophils <300/μL [low] vs ≥300/μL [high]) and baseline markers of asthma severity (emergency asthma treatment in prior year, asthma hospitalization in prior year, forced expiratory volume in 1 second [FEV ; FEV <65% vs ≥65% predicted], inhaled beclomethasone dipropionate dose [<600 vs ≥600 μg/day], and long-acting beta-agonist [LABA] use [yes/no]).
Adults/adolescents (N = 1071) were randomized to receive either omalizumab (n = 542) or placebo (n = 529). In the 16-week ICS dose-stable phase, rates of exacerbations requiring ≥3 days of systemic corticosteroid treatment were 0.066 and 0.147 with omalizumab and placebo, respectively, representing a relative rate reduction in omalizumab-treated patients of 55% (95% CI, 32%-70%; P = .002). For patients with eosinophils ≥300/μL or with more severe asthma, this rate reduction was significantly more pronounced.
In patients with allergic asthma, baseline blood eosinophil levels and/or clinical markers of asthma severity predict response to omalizumab.
最近的哮喘生物制剂疗效研究纳入了高度富集的患者人群。我们采用类似的方法，研究了预测奥马珠单抗应答的相关因素，以帮助选择最有可能从治疗中获益最大的患者。
对奥马珠单抗治疗过敏性哮喘的两项 III 期临床试验的数据进行了分析。在吸入性皮质激素（ICS）剂量稳定的 16 周期间，奥马珠单抗组和安慰剂组之间哮喘加重的发生率存在差异，其与基线时的血嗜酸性粒细胞计数（嗜酸性粒细胞<300/μL[低]与≥300/μL[高]）和基线时的哮喘严重程度标志物（前一年接受过紧急哮喘治疗、前一年住院治疗、1 秒用力呼气容积（FEV；FEV<65%预测值与≥65%预测值）、吸入性丙酸倍氯米松剂量（<600 与≥600μg/天）和长效β激动剂（LABA）使用（是/否））有关。
成年人/青少年（N=1071）被随机分为奥马珠单抗组（n=542）或安慰剂组（n=529）。在 ICS 剂量稳定的 16 周期间，需要接受≥3 天全身皮质激素治疗的哮喘加重率分别为奥马珠单抗组 0.066 和安慰剂组 0.147，奥马珠单抗治疗组的相对减少率为 55%（95%置信区间，32%-70%；P=0.002）。对于嗜酸性粒细胞≥300/μL或哮喘更严重的患者，这种降低更为明显。
在过敏性哮喘患者中，基线时的血嗜酸性粒细胞水平和/或哮喘严重程度的临床标志物可预测奥马珠单抗的应答。
