重度嗜酸性粒细胞哮喘中IL-5通路抑制剂治疗应答的表型预测因素：一项回顾性真实世界队列研究

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中文摘要

目的： 旨在确定成人重度嗜酸性粒细胞哮喘患者对白细胞介素-5（IL-5）通路抑制剂治疗应答的真实世界临床和表型预测因素。
方法： 在这项回顾性队列研究中，2019年6月至2025年6月期间，128名接受美泊利单抗或贝那利珠单抗治疗的重度嗜酸性粒细胞哮喘成人患者被随访至少12个月。治疗应答采用包含哮喘控制、急性发作频率和口服糖皮质激素减量的多维复合结局进行评估。通过多变量logistic回归和敏感性分析确定应答的独立预测因素。
结果： 随访期间，大多数患者达到具有临床意义的改善。在校正分析中，基线血嗜酸性粒细胞计数被排除在主要多变量模型之外，因为其可能受到全身性糖皮质激素使用的影响。鼻息肉病（OR = 5.01；95% CI：1.28-19.59）和哮喘发病年龄较早（每增加1年OR = 0.92；95% CI：0.86-0.98）与治疗应答独立相关。在完全校正模型中，肥胖和总免疫球蛋白E（IgE）水平与应答无独立相关性。纳入基线血嗜酸性粒细胞计数和既往急性发作频率的敏感性分析得出一致结果。
结论： 鼻息肉病和较早的疾病发病年龄是与IL-5靶向生物治疗良好应答相关的关键表型标志物。这些发现支持在常规临床实践中采用以表型为导向的生物制剂选择策略和个体化管理。

英文摘要

OBJECTIVE: To identify real-world clinical and phenotypic predictors of treatment response to interleukin-5 (IL-5) pathway inhibitors in adults with severe eosinophilic asthma.
METHODS: In this retrospective cohort study, 128 adults with severe eosinophilic asthma treated with mepolizumab or benralizumab were followed for at least 12 months between June 2019 and June 2025. Treatment response was evaluated using a multidimensional composite outcome incorporating asthma control, exacerbation frequency, and oral corticosteroid reduction. Independent predictors of response were identified using multivariable logistic regression and sensitivity analyses.
RESULTS: During follow-up, most patients achieved clinically meaningful improvement. In adjusted analyses, baseline blood eosinophil counts were excluded from the primary multivariable model because they may have been influenced by systemic corticosteroid use. Nasal polyposis (OR = 5.01; 95% CI: 1.28-19.59) and earlier age at asthma onset (OR = 0.92 per year; 95% CI: 0.86-0.98) were independently associated with treatment response. Obesity and total immunoglobulin E (IgE) levels were not independently associated with response in the fully adjusted model. Sensitivity analyses incorporating baseline blood eosinophil counts and prior exacerbation frequency yielded consistent findings.
CONCLUSIONS: Nasal polyposis and earlier disease onset represent key phenotypic markers associated with a favorable response to IL-5-targeted biologic therapy. These findings support phenotype-oriented strategies for biologic selection and personalized management in routine clinical practice.