Purpose: Improved understanding of characteristics that may influence treatment response across phenotypes may help guide treatment decisions.
Patients and Methods: This was a post hoc analysis of MENSA, a multicenter, randomized, double-blind, placebo-controlled trial (NCT01691521). Patients aged ≥ 12 years with severe eosinophilic asthma received mepolizumab (75 mg intravenously or 100 mg subcutaneously) or placebo, plus standard of care, every 4 weeks for 32 weeks. Outcomes assessed were the annualized rate of clinically significant exacerbations and change from baseline in Asthma Control Questionnaire (ACQ)-5 score. Subgroup analyses were performed by baseline blood eosinophil count (< 150, ≥ 150– 300, ≥ 300 cells/μL) within atopic subgroups (non-atopic [specific immunoglobulin E < 0.35 kU/L], atopic [≥ 0.35– 17.5 kU/L], strongly atopic [> 17.5 kU/L]), and by house dust mite (HDM) sensitivity.
Results: Of 576 patients analyzed, 272 were non-atopic, 181 were atopic and 94 were strongly atopic; 29 had missing atopy data. In patients with blood eosinophil counts ≥ 300 cells/μL, mepolizumab versus placebo reduced clinically significant exacerbations by 74%, 43% and 25% in the non-atopic, atopic and strongly atopic subgroups. Similar reductions were observed in all atopic subgroups in other blood eosinophil count categories where there were sufficient patient numbers for analysis, except for non-atopic patients with baseline blood eosinophil counts of < 150 cells/μL. Improvements in ACQ-5 scores of – 0.75, – 0.73 and – 0.78 with mepolizumab versus placebo were observed in non-atopic, atopic and strongly atopic patients with blood eosinophil counts ≥ 300 cells/μL; consistent improvements in ACQ-5 were not observed in patients with blood eosinophil counts < 150 or ≥ 150– 300 cells/μL. Reductions in clinically significant exacerbations with mepolizumab versus placebo were also observed irrespective of sensitivity to HDMs.
Conclusion: Mepolizumab was associated with a trend for reductions in clinically significant exacerbations and improved asthma control versus placebo in patients with severe eosinophilic asthma, irrespective of atopic status or HDM sensitivity.

Keywords: allergens and epitopes, eosinophils, asthma, asthma treatments, biologics

中文翻译：

---

重度嗜酸性哮喘和特应性表型患者对美泊利单抗治疗的反应

目的：提高对可能影响不同表型治疗反应的特征的理解可能有助于指导治疗决策。
患者和方法：这是对 MENSA 的事后分析，这是一项多中心、随机、双盲、安慰剂对照试验 (NCT01691521)。年龄≥12 岁的重度嗜酸性粒细胞性哮喘患者每 4 周接受一次美泊利单抗（75 mg 静脉注射或 100 mg 皮下注射）或安慰剂加标准治疗，持续 32 周。评估的结果是临床显着恶化的年化率和哮喘控制问卷 (ACQ)-5 评分相对于基线的变化。通过特应性亚组（非特应性 [特异性免疫球蛋白 E < 0.35 kU/L]、特应性 [≥ 0.35-17.5 kU/ L]、强特应性 [> 17.5 kU/L]）和屋尘螨 (HDM) 敏感性。
结果：在分析的 576 名患者中，272 名非特应性，181 名特应性和 94 名强特应性；29 人缺少特应性数据。在血液嗜酸性粒细胞计数 ≥ 300 个细胞/μL 的患者中，美泊利单抗与安慰剂相比，在非特应性、特应性和强特应性亚组中将临床上显着的恶化减少了 74%、43% 和 25%。除了基线血嗜酸性粒细胞计数 < 150 细胞/μL 的非特应性患者外，在其他血嗜酸性粒细胞计数类别的所有特应性亚组中也观察到了类似的减少，其中有足够的患者数量进行分析。在血液嗜酸性粒细胞计数 ≥ 300 细胞/μL 的非特应性、特应性和强特应性患者中，观察到美泊利单抗与安慰剂相比 ACQ-5 评分分别提高了 – 0.75、– 0.73 和 – 0.78；在血嗜酸性粒细胞计数 < 150 或 ≥ 150–300 个细胞/μL 的患者中未观察到 ACQ-5 的持续改善。无论对 HDM 的敏感性如何，美泊利单抗与安慰剂相比也观察到临床显着恶化的减少。
结论：无论特应性状态或 HDM 敏感性如何，与安慰剂相比，Mepolizumab 与严重嗜酸性粒细胞性哮喘患者临床显着恶化和改善哮喘控制的趋势相关。

关键词：过敏原和表位，嗜酸性粒细胞，哮喘，哮喘治疗，生物制剂