Voskamp Astrid L, Gillman Andrew, Symons Karen, Sandrini Alessandra, Rolland Jennifer M, O'Hehir Robyn E, Douglass Jo A
Department of Allergy, Immunology and Respiratory Medicine, Alfred Hospital and Monash University, Melbourne, Australia; Department of Immunology, Monash University, Melbourne, Australia.
Department of Allergy, Immunology and Respiratory Medicine, Alfred Hospital and Monash University, Melbourne, Australia.
J Allergy Clin Immunol Pract. 2015 Mar-Apr;3(2):192-9. doi: 10.1016/j.jaip.2014.12.008. Epub 2015 Jan 29.
Allergic bronchopulmonary aspergillosis (ABPA) often presents with persistently uncontrolled asthma despite the use of corticosteroids and antifungal therapy. Omalizumab is a humanized anti-IgE monoclonal antibody currently used to treat severe asthma.
The aim was to assess the clinical and immunologic effects of omalizumab in ABPA in a randomized, placebo-controlled trial.
Patients with chronic ABPA were randomized to 4-month treatment with omalizumab (750 mg monthly) or placebo followed by a 3-month washout period in a cross-over design. The main endpoint was number of exacerbations. Other clinical endpoints included lung function, exhaled nitric oxide (FeNO), quality of life and symptoms. In vitro basophil activation to Aspergillus fumigatus extract and basophil FcεR1 and surface-bound IgE levels were assessed by flow cytometry.
Thirteen patients were recruited with mean total IgE 2314 ± 2125 IU/mL. Exacerbations occurred less frequently during the active treatment phase compared with the placebo period (2 vs 12 events, P = .048). Mean FeNO decreased from 30.5 to 17.1 ppb during omalizumab treatment (P = .03). Basophil sensitivity to A. fumigatus and surface-bound IgE and FcεR1 levels decreased significantly after omalizumab but not after placebo.
Omalizumab can be used safely to treat ABPA, despite high serum IgE levels. Clinical improvement was accompanied by decreased basophil reactivity to A. fumigatus and FcεR1 and surface-bound IgE levels.
变应性支气管肺曲霉病（ABPA）通常表现为尽管使用了皮质类固醇和抗真菌治疗，但哮喘仍持续无法得到控制。奥马珠单抗是一种人源化抗IgE单克隆抗体，目前用于治疗重度哮喘。
旨在通过一项随机、安慰剂对照试验评估奥马珠单抗治疗ABPA的临床和免疫学效果。
慢性ABPA患者采用交叉设计，随机接受奥马珠单抗（每月750 mg）或安慰剂治疗4个月，随后有3个月的洗脱期。主要终点是病情加重的次数。其他临床终点包括肺功能、呼出气一氧化氮（FeNO）、生活质量和症状。通过流式细胞术评估体外嗜碱性粒细胞对烟曲霉提取物的激活情况以及嗜碱性粒细胞FcεR1和表面结合IgE水平。
招募了13例患者，平均总IgE为2314±2125 IU/mL。与安慰剂期相比，在积极治疗阶段病情加重的频率较低（2次对12次事件，P = .048）。在奥马珠单抗治疗期间，平均FeNO从30.5 ppb降至17.1 ppb（P = .03）。奥马珠单抗治疗后，嗜碱性粒细胞对烟曲霉的敏感性以及表面结合IgE和FcεR1水平显著降低，但安慰剂治疗后未降低。
尽管血清IgE水平较高，奥马珠单抗仍可安全用于治疗ABPA。临床改善伴随着嗜碱性粒细胞对烟曲霉的反应性以及FcεR1和表面结合IgE水平的降低。
