度普利尤单抗的疗效和度普利尤单抗诱导的重症哮喘嗜酸性粒细胞增多的危险因素：来自中国的初步研究
2024/10/29
摘要
目的：度普利尤单抗已被批准通过抑制白细胞介素（IL）-4和IL-13信号传导来治疗2型炎症的严重哮喘。然而，已经报道了度普利尤单抗诱导的嗜酸性粒细胞增多（HE），不应忽视。本研究的目的是调查度普利尤单抗在中国重症哮喘患者中的疗效，他是否影响其疗效，以及HE的可能危险因素。
方法：纳入2019 - 2022年在广州医科大学第一附属医院接受度普利尤单抗治疗至少12个月的20例重症哮喘患者。我们比较了度普利尤单抗治疗前和治疗后4个月和12个月的临床数据和实验室检查结果。根据度普利尤单抗治疗是否触发HE(定义为血嗜酸性粒细胞计数（BEC)≥1.5 × 10(9)个细胞/L），将患者分为非HE组和HE组。
结果：患者在接受度普利尤单抗治疗4个月和12个月后，哮喘控制试验（ACT）评分显著增加，加重次数减少，口服皮质类固醇（OCS）患者比例和剂量减少，肺功能参数FEV1/FVC（%）和FEV1（%预测）显著改善。对于2型炎症生物标志物，呼气一氧化氮（FeNO）分数浓度水平、痰嗜酸性粒细胞计数百分比（SEC%）和总免疫球蛋白E（TIgE）水平显著下降，而BEC在治疗4个月后较高，但在12个月后恢复到基线水平。8例患者（40%）在度普利尤单抗治疗后出现无症状HE， HE组与非HE组疗效无显著差异。BEC升高最早出现在治疗后1个月，但多数在6个月后下降，在治疗12个月左右基本恢复到基线水平。此外，我们进一步发现，当患者FeNO≥60 ppb，食物过敏原阳性并合并嗜酸性中耳炎（EOM）时，在治疗4个月和12个月后，其BEC明显高于对照组。
结论：本研究表明，度普利尤单抗对中国重症哮喘患者有效，部分患者出现无症状、自限性HE，不影响其疗效。此外，FeNO≥60ppb、食物过敏原阳性、与EOM合并症可能是HE发生的危险因素。
Efficacy of dupilumab and risk factors for dupilumab-induced hypereosinophilia in severe asthma: a preliminary study from China.
You, Li; Zhenan, Deng; Junjie, Wen;
Abstrast
Objective: Dupilumab has been approved for the treatment of severe asthma with type 2 inflammation by inhibiting interleukin (IL)-4 and IL-13 signaling. However, dupilumab-induced hypereosinophilia (HE) has been reported and should not be ignored. The aim of this study was to investigate the efficacy of dupilumab in Chinese patients with severe asthma, whether HE affects its efficacy, and the possible risk factors for HE.
Methods: 20 patients with severe asthma who received dupilumab treatment for at least 12 months in the First Affiliated Hospital of Guangzhou Medical University from 2019 to 2022 were included. We compared clinical data and laboratory tests results before dupilumab treatment and at 4 and 12 months after treatment. Based on whether dupilumab treatment triggers HE defined as blood eosinophil count (BEC) ≥ 1.5 × 10(9) cells/L, the patients were allocated into non-HE and HE groups.
Results：The patients showed a significant increase in asthma control test (ACT) scores, a decrease in the number of exacerbations, a decrease in the proportion of patients taking an oral corticosteroid (OCS) and in the dose, and a significant improvement in the pulmonary function parameters FEV1/FVC (%) and FEV1 (% predicted) after 4 and 12 months of treatment with dupilumab. For type 2 inflammatory biomarkers, the levels of fractional concentration of exhaled nitric oxide (FeNO), sputum eosinophil count percentage (SEC%) and total immunoglobulin E (TIgE) decreased significantly, whereas BEC were higher after 4 months of treatment, but returned to baseline levels after 12 months. 8 patients (40%) developed asymptomatic HE after dupilumab, and the efficacy was not significantly different between the HE and non-HE groups. The earliest BEC elevation appeared at 1 month after treatment, but most of them declined after 6 months, and basically returned to the baseline level around 12 months of treatment. In addition, we further found that when patients had FeNO ≥ 60 ppb, food allergens positive and combined eosinophilic otitis media (EOM), their BEC increased significantly more than that of the control group after 4 months as well as 12 months of treatment.
Conclusions: This study demonstrated that dupilumab was efficacious in Chinese patients with severe asthma, and some patients developed asymptomatic, self-limited HE, which did not affect its efficacy. Additionally, FeNO ≥60 ppb, food allergens positive, and co-morbidities with EOM may be the risk factors for developing HE.
目的：度普利尤单抗已被批准通过抑制白细胞介素（IL）-4和IL-13信号传导来治疗2型炎症的严重哮喘。然而，已经报道了度普利尤单抗诱导的嗜酸性粒细胞增多（HE），不应忽视。本研究的目的是调查度普利尤单抗在中国重症哮喘患者中的疗效，他是否影响其疗效，以及HE的可能危险因素。
方法：纳入2019 - 2022年在广州医科大学第一附属医院接受度普利尤单抗治疗至少12个月的20例重症哮喘患者。我们比较了度普利尤单抗治疗前和治疗后4个月和12个月的临床数据和实验室检查结果。根据度普利尤单抗治疗是否触发HE(定义为血嗜酸性粒细胞计数（BEC)≥1.5 × 10(9)个细胞/L），将患者分为非HE组和HE组。
结果：患者在接受度普利尤单抗治疗4个月和12个月后，哮喘控制试验（ACT）评分显著增加，加重次数减少，口服皮质类固醇（OCS）患者比例和剂量减少，肺功能参数FEV1/FVC（%）和FEV1（%预测）显著改善。对于2型炎症生物标志物，呼气一氧化氮（FeNO）分数浓度水平、痰嗜酸性粒细胞计数百分比（SEC%）和总免疫球蛋白E（TIgE）水平显著下降，而BEC在治疗4个月后较高，但在12个月后恢复到基线水平。8例患者（40%）在度普利尤单抗治疗后出现无症状HE， HE组与非HE组疗效无显著差异。BEC升高最早出现在治疗后1个月，但多数在6个月后下降，在治疗12个月左右基本恢复到基线水平。此外，我们进一步发现，当患者FeNO≥60 ppb，食物过敏原阳性并合并嗜酸性中耳炎（EOM）时，在治疗4个月和12个月后，其BEC明显高于对照组。
结论：本研究表明，度普利尤单抗对中国重症哮喘患者有效，部分患者出现无症状、自限性HE，不影响其疗效。此外，FeNO≥60ppb、食物过敏原阳性、与EOM合并症可能是HE发生的危险因素。
(中日友好医院呼吸与危重症医学科 万静萱 摘译 林江涛 审校)
(Ann Med 2024 Dec;56(1):2311843. DOI: 10.1080/07853890.2024.2311843.IF：3.243)
(Ann Med 2024 Dec;56(1):2311843. DOI: 10.1080/07853890.2024.2311843.IF：3.243)
Efficacy of dupilumab and risk factors for dupilumab-induced hypereosinophilia in severe asthma: a preliminary study from China.
You, Li; Zhenan, Deng; Junjie, Wen;
Abstrast
Objective: Dupilumab has been approved for the treatment of severe asthma with type 2 inflammation by inhibiting interleukin (IL)-4 and IL-13 signaling. However, dupilumab-induced hypereosinophilia (HE) has been reported and should not be ignored. The aim of this study was to investigate the efficacy of dupilumab in Chinese patients with severe asthma, whether HE affects its efficacy, and the possible risk factors for HE.
Methods: 20 patients with severe asthma who received dupilumab treatment for at least 12 months in the First Affiliated Hospital of Guangzhou Medical University from 2019 to 2022 were included. We compared clinical data and laboratory tests results before dupilumab treatment and at 4 and 12 months after treatment. Based on whether dupilumab treatment triggers HE defined as blood eosinophil count (BEC) ≥ 1.5 × 10(9) cells/L, the patients were allocated into non-HE and HE groups.
Results：The patients showed a significant increase in asthma control test (ACT) scores, a decrease in the number of exacerbations, a decrease in the proportion of patients taking an oral corticosteroid (OCS) and in the dose, and a significant improvement in the pulmonary function parameters FEV1/FVC (%) and FEV1 (% predicted) after 4 and 12 months of treatment with dupilumab. For type 2 inflammatory biomarkers, the levels of fractional concentration of exhaled nitric oxide (FeNO), sputum eosinophil count percentage (SEC%) and total immunoglobulin E (TIgE) decreased significantly, whereas BEC were higher after 4 months of treatment, but returned to baseline levels after 12 months. 8 patients (40%) developed asymptomatic HE after dupilumab, and the efficacy was not significantly different between the HE and non-HE groups. The earliest BEC elevation appeared at 1 month after treatment, but most of them declined after 6 months, and basically returned to the baseline level around 12 months of treatment. In addition, we further found that when patients had FeNO ≥ 60 ppb, food allergens positive and combined eosinophilic otitis media (EOM), their BEC increased significantly more than that of the control group after 4 months as well as 12 months of treatment.
Conclusions: This study demonstrated that dupilumab was efficacious in Chinese patients with severe asthma, and some patients developed asymptomatic, self-limited HE, which did not affect its efficacy. Additionally, FeNO ≥60 ppb, food allergens positive, and co-morbidities with EOM may be the risk factors for developing HE.
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