Magnan A, Bourdin A, Prazma C M, Albers F C, Price R G, Yancey S W, Ortega H
INSERM UMR 1087 CNRS UMR 6291, L'Institut du Thorax, CHU de Nantes, Université de Nantes, Nantes, France.
Département de Pneumologie et Addictologie, INSERM U1046, CNRS UMR 9214, Hôpital Arnaud de Villeneuve CHU Montpellier, and PhyMedExp, University of Montpellier, Montpellier, France.
Allergy. 2016 Sep;71(9):1335-44. doi: 10.1111/all.12914. Epub 2016 May 24.
We performed post hoc analyses to evaluate the effect of humanized monoclonal antibody mepolizumab in patients with severe eosinophilic asthma previously treated with omalizumab.
Data were collected from two randomized double-blind, placebo-controlled studies: MENSA (NCT01691521: 32-week treatment phase) and SIRIUS (NCT01691508: 24-week treatment phase). Active treatment was 75 mg intravenous mepolizumab (MENSA) or 100 mg subcutaneous mepolizumab (MENSA, SIRIUS). Patients had evidence of eosinophilic inflammation ≥150 cells/μl (at screening) or ≥300 cells/μl (during the previous year). Primary outcomes were the rate of exacerbations (MENSA) and the percentage reduction in oral corticosteroid (OCS) dose (SIRIUS). Other outcomes included lung function (forced expiratory volume in 1 s and morning peak expiratory flow), Asthma Control Questionnaire (ACQ-5), St George's Respiratory Questionnaire (SGRQ) scores, and safety.
Overall, 576 patients were included from MENSA and 135 from SIRIUS, with 13% and 33% previously receiving omalizumab, respectively. In MENSA, mepolizumab reduced the rate of exacerbations by 57% (prior omalizumab) and 47% (no prior omalizumab) vs placebo. In SIRIUS, reductions in OCS use were comparable regardless of prior omalizumab use. Despite reducing chronic OCS use, mepolizumab also resulted in similar reductions in exacerbation rate relative to placebo in both subgroups. Asthma control and quality of life improved with mepolizumab vs placebo in both studies independent of prior omalizumab use, as shown by ACQ-5 and SGRQ scores. Adverse events were also comparable irrespective of prior omalizumab use.
These post hoc analyses indicate that patients with severe eosinophilic asthma respond positively to mepolizumab regardless of prior use of omalizumab.
我们进行了事后分析，以评估人源化单克隆抗体美泊利珠单抗对先前接受奥马珠单抗治疗的重度嗜酸性粒细胞性哮喘患者的疗效。
数据来自两项随机双盲、安慰剂对照研究：MENSA（NCT01691521：32周治疗期）和SIRIUS（NCT01691508：24周治疗期）。活性治疗为静脉注射75mg美泊利珠单抗（MENSA）或皮下注射100mg美泊利珠单抗（MENSA、SIRIUS）。患者有嗜酸性粒细胞炎症证据≥150个细胞/μl（筛查时）或≥300个细胞/μl（前一年期间）。主要结局为恶化率（MENSA）和口服糖皮质激素（OCS）剂量降低百分比（SIRIUS）。其他结局包括肺功能（第1秒用力呼气量和早晨呼气峰值流速）、哮喘控制问卷（ACQ-5）、圣乔治呼吸问卷（SGRQ）评分和安全性。
总体而言，MENSA纳入了576例患者，SIRIUS纳入了135例患者，分别有13%和33%的患者先前接受过奥马珠单抗治疗。在MENSA中，与安慰剂相比，美泊利珠单抗使恶化率降低了57%（先前使用过奥马珠单抗）和47%（未先前使用过奥马珠单抗）。在SIRIUS中，无论先前是否使用过奥马珠单抗，OCS使用的减少情况相当。尽管减少了慢性OCS的使用，但在两个亚组中，与安慰剂相比，美泊利珠单抗导致的恶化率降低情况也相似。如ACQ-5和SGRQ评分所示，在两项研究中，与安慰剂相比，美泊利珠单抗均改善了哮喘控制和生活质量，且与先前是否使用过奥马珠单抗无关。无论先前是否使用过奥马珠单抗，不良事件也相当。
这些事后分析表明，重度嗜酸性粒细胞性哮喘患者无论先前是否使用过奥马珠单抗，对美泊利珠单抗均有积极反应。
