重度哮喘治疗中“生物学缓解”作为治疗目标的临床观察研究：基于英国重度哮喘注册数据的分析
2026/02/06
背景：重度哮喘生物制剂治疗的主要目标是抑制2型（T2）炎症通路。
目的：本研究假设，通过生物制剂治疗实现 IL-5及IL-4/IL-13通路完全抑制的患者（定义为“生物学缓解”：呼出气一氧化氮 [FeNO] < 20 ppb 且血嗜酸性粒细胞（EOS）计数 < 0.15 × 109/L），其临床预后优于 T2生物学特征抑制不完全的患者。
方法：本研究对英国重度哮喘注册中心（UKSAR）中符合国家严格生物制剂使用标准的重度哮喘患者进行了回顾性分析。对比了生物学缓解（BR）组与非生物学缓解（non-BR）组在基线期（生物制剂治疗前）及年度随访时的临床特征差异。
结果：在778例患者中，148 例（19%）实现 BR，630例（81%）未实现BR。结果显示，BR组在降低急性加重风险、减少口服激素的使用、改善症状和肺功能或进一步降低T2生物标志物等方面并没有额外获益。BR组患者在接受生物制剂治疗前的基线T2炎症水平较低。多因素分析显示，病程长（调整后比值比 [adjOR] = 1.96；95% CI: 1.17-3.28）、大环内酯类药物治疗史（adjOR = 2.08；95% CI: 1.17-3.71）以及吸烟史（adjOR = 1.63；95% CI: 1.11-2.39）是实现BR 的正向预测因子；而基线T2生物标志物高水平则是实现BR对的负向预测因子。血EOS计数和 FeNO水平与肺功能均呈负相关。
结论：与未达到生物学缓解的患者相比，达到生物学缓解的患者并未在急性发作、口服激素使用、症状控制或肺功能改善等方面表现出额外获益。生物学缓解主要识别了基线T2炎症水平较低、但可能存在其他疾病驱动因素的患者亚群。尽管完全抑制T2通路未带来超越常规治疗的临床优势，但T2生物标志物水平与肺功能仍呈负相关，提示抑制T2炎症本身对肺功能改善有重要意义。未来有必要在T2高水平患者中进一步开展前瞻性研究，评估完全抑制IL-5与IL-4/IL-13通路的治疗价值。
关键词：哮喘；2 型炎症；缓解；UKSAR；生物制剂；单克隆抗体
Observational Analysis of Biological Remission as a Treatment Target for Severe Asthma: UK Severe Asthma Registry
Abstract
Background: The aim of biologic therapies in severe asthma is inhibition of type 2 (T2) inflammatory pathways.
Objective: We hypothesized that patients who achieve complete suppression of IL-5 and IL-4/IL-13 pathways with biologic therapy (FeNO <20 ppb and blood eosinophil count <0.15 × 109, considered biological remission) would have better outcomes than patients with incomplete suppression of T2 biology.
Methods: This was a retrospective analysis of patients with severe asthma in the United Kingdom Severe Asthma Registry who met strict national access criteria for biologics. Characteristics before the biologic and at annual review were compared across biologic remission (BR) and non-BR.
Results: Of 778 patients, 148 (19%) had BR and 630 (81%) non-BR. Biologic remission did not confer additional benefit in exacerbation reduction, oral steroid exposure, lung function improvement, symptom improvement, or T2 biomarker reduction. The BR cohort was less T2 high before commencing biologics. Long disease duration (adjusted odds ratio [adjOR] = 1.96; 95% CI, 1.17-3.28), macrolide therapy (adjOR = 2.08; 95% CI, 1.17-3.71), and smoking history (adjOR = 1.63; 95% CI, 1.11-2.39) were positive predictors of BR, whereas higher T2 biomarkers predicted non-BR. However, blood eosinophil count and FeNO both had a negative correlation with lung function.
Conclusion: Patients who achieve BR do not have superior outcomes compared with those who do not achieve BR. Biologic remission denotes a cohort of patients with a lower burden of T2 disease and additional factors driving disease severity. However, suppression of T2 biology is important for lung function gain. Prospective evaluation of treatment strategies that completely suppress IL-5 and IL-4/IL-13 pathways in T2 composite–high patients is needed.
Key words: Asthma; Type 2 inflammation; Remission; UKSAR; Biologics; Monoclonal antibodies
目的：本研究假设，通过生物制剂治疗实现 IL-5及IL-4/IL-13通路完全抑制的患者（定义为“生物学缓解”：呼出气一氧化氮 [FeNO] < 20 ppb 且血嗜酸性粒细胞（EOS）计数 < 0.15 × 109/L），其临床预后优于 T2生物学特征抑制不完全的患者。
方法：本研究对英国重度哮喘注册中心（UKSAR）中符合国家严格生物制剂使用标准的重度哮喘患者进行了回顾性分析。对比了生物学缓解（BR）组与非生物学缓解（non-BR）组在基线期（生物制剂治疗前）及年度随访时的临床特征差异。
结果：在778例患者中，148 例（19%）实现 BR，630例（81%）未实现BR。结果显示，BR组在降低急性加重风险、减少口服激素的使用、改善症状和肺功能或进一步降低T2生物标志物等方面并没有额外获益。BR组患者在接受生物制剂治疗前的基线T2炎症水平较低。多因素分析显示，病程长（调整后比值比 [adjOR] = 1.96；95% CI: 1.17-3.28）、大环内酯类药物治疗史（adjOR = 2.08；95% CI: 1.17-3.71）以及吸烟史（adjOR = 1.63；95% CI: 1.11-2.39）是实现BR 的正向预测因子；而基线T2生物标志物高水平则是实现BR对的负向预测因子。血EOS计数和 FeNO水平与肺功能均呈负相关。
结论：与未达到生物学缓解的患者相比，达到生物学缓解的患者并未在急性发作、口服激素使用、症状控制或肺功能改善等方面表现出额外获益。生物学缓解主要识别了基线T2炎症水平较低、但可能存在其他疾病驱动因素的患者亚群。尽管完全抑制T2通路未带来超越常规治疗的临床优势，但T2生物标志物水平与肺功能仍呈负相关，提示抑制T2炎症本身对肺功能改善有重要意义。未来有必要在T2高水平患者中进一步开展前瞻性研究，评估完全抑制IL-5与IL-4/IL-13通路的治疗价值。
关键词：哮喘；2 型炎症；缓解；UKSAR；生物制剂；单克隆抗体
（南方医科大学南方医院 胡玉玲 龚钊乾 赵海金）
（McDowell PJ, Redmond C, Busby J, et al. Observational Analysis of Biological Remission as a Treatment Target for Severe Asthma: UK Severe Asthma Registry. J Allergy Clin Immunol Pract. 2025;13(12):3264-3273.e10. doi:10.1016/j.jaip.2025.08.027）
（McDowell PJ, Redmond C, Busby J, et al. Observational Analysis of Biological Remission as a Treatment Target for Severe Asthma: UK Severe Asthma Registry. J Allergy Clin Immunol Pract. 2025;13(12):3264-3273.e10. doi:10.1016/j.jaip.2025.08.027）
Observational Analysis of Biological Remission as a Treatment Target for Severe Asthma: UK Severe Asthma Registry
Abstract
Background: The aim of biologic therapies in severe asthma is inhibition of type 2 (T2) inflammatory pathways.
Objective: We hypothesized that patients who achieve complete suppression of IL-5 and IL-4/IL-13 pathways with biologic therapy (FeNO <20 ppb and blood eosinophil count <0.15 × 109, considered biological remission) would have better outcomes than patients with incomplete suppression of T2 biology.
Methods: This was a retrospective analysis of patients with severe asthma in the United Kingdom Severe Asthma Registry who met strict national access criteria for biologics. Characteristics before the biologic and at annual review were compared across biologic remission (BR) and non-BR.
Results: Of 778 patients, 148 (19%) had BR and 630 (81%) non-BR. Biologic remission did not confer additional benefit in exacerbation reduction, oral steroid exposure, lung function improvement, symptom improvement, or T2 biomarker reduction. The BR cohort was less T2 high before commencing biologics. Long disease duration (adjusted odds ratio [adjOR] = 1.96; 95% CI, 1.17-3.28), macrolide therapy (adjOR = 2.08; 95% CI, 1.17-3.71), and smoking history (adjOR = 1.63; 95% CI, 1.11-2.39) were positive predictors of BR, whereas higher T2 biomarkers predicted non-BR. However, blood eosinophil count and FeNO both had a negative correlation with lung function.
Conclusion: Patients who achieve BR do not have superior outcomes compared with those who do not achieve BR. Biologic remission denotes a cohort of patients with a lower burden of T2 disease and additional factors driving disease severity. However, suppression of T2 biology is important for lung function gain. Prospective evaluation of treatment strategies that completely suppress IL-5 and IL-4/IL-13 pathways in T2 composite–high patients is needed.
Key words: Asthma; Type 2 inflammation; Remission; UKSAR; Biologics; Monoclonal antibodies
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