Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA.
Analysis Group, Montreal, Quebec, Canada.
Clin Ther. 2019 Oct;41(10):1956-1971. doi: 10.1016/j.clinthera.2019.07.021. Epub 2019 Sep 25.
Biomarkers, including blood eosinophils (EoS) and fractional exhaled nitric oxide (FeNO), may affect omalizumab outcomes in allergic asthma, but evidence in the literature remains mixed. This study assessed omalizumab outcomes in real-world patients with allergic asthma stratified by pretreatment biomarker levels.
Patients with allergic asthma aged ≥12 years initiated on omalizumab with ≥12 months of data after index were identified in the Allergy Partners electronic medical records (2007-2018). Patients with ≥1 diagnosis of chronic obstructive pulmonary disease in combination with ≥10 pack-years of smoking, cystic fibrosis, Alpha-1 antitrypsin deficiency, bronchiectasis, interstitial lung disease, and sarcoidosis in the 12 months before or after index were excluded. Patients were stratified by pretreatment EoS (≥/<300 cells/μL) and FeNO (≥/<25 parts per billion). Outcomes, including Asthma Control Test (ACT) scores, forced expiratory volume in 1 second (FEV), and FEV as a percentage of predicted value (FEV% predicted), were compared using generalized estimating equations at 6 and 12 months after versus before index date in stratified patients with outcome measures available at both time periods.
A total of 77 and 86 patients were stratified into the high and low EoS strata, respectively, and 56 patients into each of the intermediate-high and low FeNO strata. Compared with 6 months before index, mean difference (MD) in ACT scores at 6 months after index reached the minimally important difference of ≥3 points in high (MD = 3.75; 95% CI, 2.05-5.45) and low (MD = 4.56; 95% CI, 2.86-6.26) EoS, as well in the intermediate-high (MD = 3.75; 95% CI, 1.95-5.55) and low (MD = 3.55; 95% CI, 1.53-5.57) FeNO strata. Statistically significant improvements in mean FEV were observed in the high EoS (MD = 0.22 L/s; 95% CI, 0.08-0.35 L/s) and intermediate-high FeNO (MD = 0.13 L/s; 95% CI, 0.03-0.24 L/s) strata but not in the lower strata. In terms of mean FEV% predicted, a statistically significant improvement was observed in high EoS stratum (MD = 4.95%; 95% CI, 0.60%-9.30%). Results that compared 12 months after versus before index date were similar.
Omalizumab was associated with statistically significant improvements in ACT scores largely reaching or exceeding minimally important difference across biomarker levels and with a statistically significant improvement in lung function more evident in high biomarker strata. Although response varied by biomarkers for some outcomes, all strata indicated improvements on ≥1 measure. Real-world patients with allergic asthma could benefit from omalizumab regardless of pretreatment biomarker levels, suggesting that pretreatment biomarker levels might not inform response.
生物标志物，包括血嗜酸性粒细胞（EOS）和呼出气一氧化氮分数（FeNO），可能会影响奥马珠单抗在过敏性哮喘中的疗效，但文献中的证据仍存在差异。本研究评估了根据治疗前生物标志物水平分层的过敏性哮喘真实世界患者中奥马珠单抗的疗效。
在过敏伙伴的电子病历中（2007-2018 年），确定了年龄≥12 岁且在索引后有≥12 个月数据的开始接受奥马珠单抗治疗的过敏性哮喘患者。排除索引前或索引后 12 个月内合并≥1 次慢性阻塞性肺疾病合并≥10 包年吸烟史、囊性纤维化、α-1 抗胰蛋白酶缺乏症、支气管扩张症、间质性肺病和结节病的患者。根据治疗前 EOS（≥/＜300 个细胞/μL）和 FeNO（≥/＜25 部分/十亿）将患者分层。在两个时间点均有疗效测量值的分层患者中，使用广义估计方程比较索引日期前后 6 个月和 12 个月时的哮喘控制测试（ACT）评分、用力呼气量（FEV）和 FEV 占预计值的百分比（FEV%预测值）等疗效。
分别有 77 例和 86 例患者分层为高 EOS 组和低 EOS 组，56 例患者分别分层为中高 FeNO 组和低 FeNO 组。与索引前 6 个月相比，索引后 6 个月的 ACT 评分在高 EOS 组（MD=3.75；95%CI，2.05-5.45）和低 EOS 组（MD=4.56；95%CI，2.86-6.26）中达到了至少 3 分的最小临床重要差异，在中高 EOS 组（MD=3.75；95%CI，1.95-5.55）和低 FeNO 组（MD=3.55；95%CI，1.53-5.57）中也达到了最小临床重要差异。高 EOS 组（MD=0.22 L/s；95%CI，0.08-0.35 L/s）和中高 FeNO 组（MD=0.13 L/s；95%CI，0.03-0.24 L/s）的平均 FEV 显著改善，但在较低的 EOS 组中没有。就平均 FEV%预测值而言，高 EOS 组有统计学意义的改善（MD=4.95%；95%CI，0.60%-9.30%）。比较索引日期前后 12 个月的结果相似。
奥马珠单抗与 ACT 评分的统计学显著改善相关，在很大程度上达到或超过了生物标志物水平的最小临床重要差异，并且在肺功能方面的统计学显著改善更为明显，在高生物标志物水平组更为明显。尽管某些结果的生物标志物存在差异，但所有分层都表明在至少 1 个指标上有所改善。无论治疗前的生物标志物水平如何，患有过敏性哮喘的真实世界患者都可能从奥马珠单抗中获益，这表明治疗前的生物标志物水平可能无法反映治疗反应。
