Sacks Peta-Lee, Meerwein Christian M, Earls Peter, Thiel Cedric, Choy Christine, Campbell Raewyn G, Sacks Raymond, Kalish Larry, Harvey Richard J
Rhinology and Skull Base Research Group, St Vincent's Centre for Applied Medical Research, University of New South Wales, Sydney, Australia.
Faculty of Medicine and Health Sciences, Macquarie University, Sydney, Australia.
Int Forum Allergy Rhinol. 2025 Jun;15(6):602-607. doi: 10.1002/alr.23534. Epub 2025 Jan 19.
Type 2 inflammation dominates eosinophilic chronic rhinosinusitis (eCRS) and adult onset asthma. IL-4, -5, and -13 are prominent disease mediators. Disease control can be achieved with biologic therapies. However, despite some patients entering remission, others experience poor control.
We aimed to describe eCRS patients treated with anti-IL-5R antibody (benralizumab) and assess characteristics between responders and those requiring class switching to anti-IL-4/13R (dupilumab).
A retrospective cohort study was performed on consecutive adult patients with eCRS and asthma who had commenced benralizumab. Disease control was defined as controlled or poorly controlled (EPOS2020 partly control/uncontrolled). Poorly controlled patients were switched to dupilumab. Baseline and post-IL-5R characteristics including age, sex, 22-item Sinonasal Outcome Test (SNOT-22), Asthma Control Questionnaire (ACQ) score, and serum/tissue eosinophilia were assessed. Disease control post-class switching was reassessed. Factors predicting poorly controlled disease on anti-IL-5R therapy were sought.
Fifty patients were assessed (51.44 ± 12.73 years, 56% female). Poorly controlled disease on anti-IL-5R requiring class switch to dupilumab was seen in 42%. Poorly controlled patients were younger (46.14 ± 10.76 vs. 55.28 ± 12.83 years, p = 0.01) with higher baseline SNOT-22 (61.42 ± 19.19 vs. 42.32 ± 21.55, p < 0.01). Baseline ACQ scores and eosinophil count (0.78 ± 0.49 vs. 0.62 ± 0.34 × 10cells/L, p = 0.23) and were similar between groups. In the poorly controlled patients on anti-IL-5R therapy, eosinophilia had reduced in both serum (0.78 ± 0.5 vs. 0.02 ± 0.1 × 10cells/L, p < 0.01) and tissue (>100 cells/HPF: 100% vs. 29%, p = 0.01). Class switching resulted in disease control for 65%.
Neither eosinophilia nor its reduction predicted a non-responder group to anti-IL-5R therapy. While the eosinophil population may be a good marker for the CRS phenotype seen in nasal polyps, it is unlikely to be the cell population driving the disease process.
2型炎症在嗜酸性粒细胞性慢性鼻-鼻窦炎（eCRS）和成人起病的哮喘中占主导地位。白细胞介素-4、-5和-13是主要的疾病介质。生物疗法可实现疾病控制。然而，尽管一些患者进入缓解期，但另一些患者控制不佳。
我们旨在描述接受抗白细胞介素-5受体抗体（贝那利珠单抗）治疗的eCRS患者，并评估应答者与需要换用抗白细胞介素-4/13受体（度普利尤单抗）治疗者之间的特征。
对连续的成年eCRS和哮喘患者进行回顾性队列研究，这些患者已开始使用贝那利珠单抗治疗。疾病控制定义为控制良好或控制不佳（根据《2020年欧洲鼻窦炎和鼻息肉立场文件》部分控制/未控制）。控制不佳的患者换用度普利尤单抗。评估基线和抗白细胞介素-5受体治疗后的特征，包括年龄、性别、22项鼻鼻窦结局测试（SNOT-22）、哮喘控制问卷（ACQ）评分以及血清/组织嗜酸性粒细胞增多情况。重新评估换用药物治疗后的疾病控制情况。寻找抗白细胞介素-5受体治疗时疾病控制不佳的预测因素。
共评估了50例患者（年龄51.44±12.73岁，56%为女性）。42%的患者在抗白细胞介素-5受体治疗时疾病控制不佳，需要换用度普利尤单抗。控制不佳的患者更年轻（46.14±10.76岁 vs. 55.28±12.83岁，p = 0.01），基线SNOT-22评分更高（61.42±19.19 vs. 42.32±21.55，p < 0.01）。基线ACQ评分和嗜酸性粒细胞计数（0.78±0.49 vs. 0.62±0.34×10⁹细胞/L，p = 0.23）在两组之间相似。在抗白细胞介素-5受体治疗控制不佳的患者中，血清嗜酸性粒细胞增多情况有所减轻（0.78±0.5 vs. 0.02±0.1×10⁹细胞/L，p < 0.01），组织中也是如此（>100个细胞/HPF：100% vs. 29%，p = 0.01）。换用药物治疗后65%的患者疾病得到控制。
嗜酸性粒细胞增多及其减少均不能预测抗白细胞介素-5受体治疗的无应答组。虽然嗜酸性粒细胞群体可能是鼻息肉中CRS表型的良好标志物，但它不太可能是驱动疾病进程的细胞群体。
