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贝那利珠单抗治疗重度过敏性嗜酸性哮喘患者的临床疗效快速显现:首剂治疗后血液嗜酸性粒细胞计数、症状控制、肺功能和口服皮质类固醇激素用量的评估。

Real-life rapidity of benralizumab effects in patients with severe allergic eosinophilic asthma: Assessment of blood eosinophils, symptom control, lung function and oral corticosteroid intake after the first drug dose.

机构信息

Department of Medical and Surgical Sciences, University "Magna Græcia" of Catanzaro, Catanzaro, Italy.

Department of Medicine, Surgery, and Dentistry, University of Salerno, Salerno, Italy.

出版信息

Pulm Pharmacol Ther. 2019 Oct;58:101830. doi: 10.1016/j.pupt.2019.101830. Epub 2019 Jul 22.

Abstract

Benralizumab is a humanized monoclonal antibody which binds to the α subunit of the interleukin-5 (IL-5) receptor and to the FcγRIIIa receptor expressed by natural killer cells, thus suppressing the pro-eosinophil actions of IL-5 and triggering eosinophil apoptosis via the very effective mechanism of antibody-dependent cell-mediated cytotoxicity (ADCC). Because of its recent approval and introduction in clinical practice for the add-on biological therapy of severe eosinophilic asthma, real-life investigations are still lacking. In this regard, our present real-life study refers to 13 patients with severe allergic eosinophilic asthma, currently under treatment with benralizumab at the Respiratory Unit of "Magna Græcia" University Hospital located in Catanzaro, Italy. Already 4 weeks after the first subcutaneous injection of benralizumab at the dosage of 30 mg, blood eosinophil count rapidly dropped down from 814.7 ± 292.3 cells/μL to 51.3 ± 97.5 cells/μL (p < 0.0001). This relevant hematologic change was associated with quick and significant increases in asthma control test (ACT) score (from 15.31 ± 2.78 to 21.15 ± 3.58; p < 0.0001), pre-bronchodilator forced expiratory volume in 1 s (FEV) (from 1441 ± 757.9 mL to 1887 ± 837.3 mL; p < 0.001), and morning peak expiratory flow (PEF) (from 4.21 ± 2.20 to 5.33 ± 1.99 L/sec; p < 0.01). Furthermore, the marked improvement in global health status experienced by our patients allowed them to progressively lower and then completely interrupt, within 4 weeks, their daily intake of oral corticosteroids (OCS), which thereby fell from 15.58 ± 8.30 to 0 mg (p < 0.0001) of prednisone. Therefore, such preliminary results suggest that in patients with severe allergic eosinophilic asthma benralizumab can exert, within a real-life context, a very rapid and effective therapeutic action, already detectable 4 weeks after the first drug administration.

摘要

贝那利珠单抗是一种人源化单克隆抗体,可与白细胞介素-5(IL-5)受体的α亚单位和自然杀伤细胞表达的 FcγRIIIa 受体结合,从而抑制 IL-5 的嗜酸性粒细胞前体作用,并通过非常有效的抗体依赖性细胞介导的细胞毒性(ADCC)触发嗜酸性粒细胞凋亡。由于其最近被批准并引入临床实践,用于严重嗜酸性粒细胞性哮喘的附加生物治疗,因此仍然缺乏真实世界的研究。在这方面,我们目前的真实研究涉及意大利卡坦扎罗“Magna Græcia”大学医院呼吸科的 13 名患有严重过敏嗜酸性哮喘的患者,他们目前正在接受贝那利珠单抗治疗。在接受贝那利珠单抗 30mg 的首次皮下注射后 4 周,血嗜酸性粒细胞计数从 814.7±292.3 细胞/μL 迅速下降至 51.3±97.5 细胞/μL(p<0.0001)。这种相关的血液学变化与哮喘控制测试(ACT)评分的快速显著增加相关(从 15.31±2.78 增加到 21.15±3.58;p<0.0001),支气管扩张剂前用力呼气量(FEV)(从 1441±757.9 毫升增加到 1887±837.3 毫升;p<0.001)和清晨呼气峰值流量(PEF)(从 4.21±2.20 增加到 5.33±1.99 升/秒;p<0.01)。此外,我们的患者经历的全球健康状况的显著改善使他们能够逐渐降低并在 4 周内完全停止每日口服皮质类固醇(OCS)的摄入,OCS 从 15.58±8.30 降至 0mg(p<0.0001)的泼尼松。因此,这些初步结果表明,在严重过敏嗜酸性哮喘患者中,贝那利珠单抗在真实环境中可以发挥非常快速和有效的治疗作用,在首次给药后 4 周即可检测到。

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