Kallieri Maria, Papaioannou Andriana I, Papathanasiou Evgenia, Ntontsi Polyxeni, Papiris Spyridon, Loukides Stelios
a 2nd Respiratory Medicine Department, "Attikon" University Hospital, Athens Medical School , National and Kapodistrian University of Athens , Greece.
Postgrad Med. 2017 Aug;129(6):598-604. doi: 10.1080/00325481.2017.1321945. Epub 2017 Apr 28.
Omalizumab is a recombinant humanized IgG1 monoclonal anti-IgE antibody, used for the treatment of severe refractory allergic asthma. However, not all patients with IgE levels within the limits of administration, respond to treatment. The aim of the present study, was to determine clinical and inflammatory characteristics that could predict response to omalizumab.
We studied retrospectively patients treated with omalizumab as per GINA guidelines in one asthma tertiary referral center. Demographic and functional characteristics, level of asthma control, fractional exhaled nitric oxide, blood and eosinophils and IgE level, induced sputum cell count, eosinophil cationic protein and Interleukin-13 in sputum supernatant were recorded. All measurements were performed before starting treatment with omalizumab. Response to treatment was evaluated according to the physician's global evaluation of treatment effectiveness. Patients were characterized as early responders when improvement was achieved within 16 weeks and as late responders when improvement was achieved between 16 and 32 weeks. Patients who did not show any improvement after 32 weeks of therapy were considered as non-responders.
Forty-one patients treated with omalizumab were included in the study. 28 (68.3%) patients were characterized as responders while 13 patients (31.7%) were considered as non-responders. Among responders, 25 (89%) were early responders and 3 (n = 11%) were late responders. Responders were characterized by lower baseline FEV and FEV/FVC and higher IL-13 levels in induced sputum supernatant compared to non-responders. Late responders had higher serum IgE levels, shorter disease duration and higher number of blood eosinophils. Finally, using ROC curve analysis, the best predictors of response to omalizumab were FEV (AUC = 0.718) and IL-13 in sputum supernatant (AUC = 0.709).
Lower baseline FEV and higher IL-13 levels in induced sputum supernatant were predictors of response to omalizumab. Patients with higher baseline serum IgE levels, shorter disease duration and higher blood eosinophils may experience a late response and might benefit from a more prolonged treatment before being characterized as non-responders.
奥马珠单抗是一种重组人源化IgG1单克隆抗IgE抗体，用于治疗重度难治性过敏性哮喘。然而，并非所有IgE水平在给药范围内的患者都对治疗有反应。本研究的目的是确定可预测对奥马珠单抗反应的临床和炎症特征。
我们回顾性研究了一家哮喘三级转诊中心按照全球哮喘防治创议（GINA）指南接受奥马珠单抗治疗的患者。记录了人口统计学和功能特征、哮喘控制水平、呼出一氧化氮分数、血液和嗜酸性粒细胞及IgE水平、诱导痰细胞计数、痰上清液中的嗜酸性粒细胞阳离子蛋白和白细胞介素-13。所有测量均在开始使用奥马珠单抗治疗前进行。根据医生对治疗效果的整体评估来评价治疗反应。在16周内病情改善的患者被归类为早期反应者，在16至32周之间病情改善的患者被归类为晚期反应者。治疗32周后未显示任何改善的患者被视为无反应者。
41例接受奥马珠单抗治疗的患者纳入研究。28例（68.3%）患者被归类为反应者，13例（31.7%）患者被视为无反应者。在反应者中，25例（89%）为早期反应者，3例（11%）为晚期反应者。与无反应者相比，反应者的特征为基线第一秒用力呼气容积（FEV）和FEV/用力肺活量（FVC）较低，诱导痰上清液中的白细胞介素-13水平较高。晚期反应者的血清IgE水平较高、病程较短且血液嗜酸性粒细胞数量较多。最后，通过ROC曲线分析，对奥马珠单抗反应的最佳预测指标是FEV（曲线下面积[AUC]=0.718）和痰上清液中的白细胞介素-13（AUC=0.709）。
基线FEV较低和诱导痰上清液中白细胞介素-13水平较高是对奥马珠单抗反应的预测指标。基线血清IgE水平较高、病程较短且血液嗜酸性粒细胞较多的患者可能会出现晚期反应，在被归类为无反应者之前可能从更长时间的治疗中获益。
