Department of Medical Specialties, Pneumology Unit, Arcispedale Santa Maria Nuova, Azienda USL di Reggio Emilia- IRCCS, 42123, Reggio Emilia, Italy.
Department of Medical Specialties, Pneumology Unit, Arcispedale Santa Maria Nuova, Azienda USL di Reggio Emilia- IRCCS, 42123, Reggio Emilia, Italy.
Pulm Pharmacol Ther. 2020 Oct;64:101966. doi: 10.1016/j.pupt.2020.101966. Epub 2020 Oct 8.
Severe eosinophilic asthma is a complex disease and much effort has been made to fully understand its mechanisms. Bronchial remodeling and loss of lung function are important features in asthma, however their key aspects are not completely clear, especially the impact that biological drugs may have on them. One of the key cytokines involved in the pathophysiology of eosinophilic asthma is interleukin-5 (IL-5), which plays a very important role together with other type 2 cytokines and chemokines in the development, transmigration and persistence of eosinophils into airways, such as eotaxin-2 and 3, thymic stromal lymphopoietin (TSLP), IL-33, as well as IL-4 and IL-13. Several monoclonal antibodies have been developed against this cytokine (mepolizumab, reslizumab) or its receptor (benralizumab). Data on the improvement of respiratory function in patients who undergo benralizumab treatment are scarce and partly conflicting. Real-life studies may play a crucial role in clarifying this important aspect. The aim of this retrospective observational real-world study was to evaluate the effect of benralizumab on lung function improvement, exacerbation rate, oral corticosteroids (OCS) reduction and asthma control questionnaire (ACQ) score before and after six months of treatment with benralizumab in a cohort of 20 consecutive patients with severe refractory asthma (SRA) treated at the Pneumology Unit of Local Health Authority, Reggio Emilia, Italy. Add-on therapy with benralizumab allowed to completely suspend OCS in 19 out of 20 patients. Notably, the number of moderate/severe exacerbations dropped significantly (p < 0,0001); as well as an improvement in ACQ score (p < 0,0001). The most relevant data concern respiratory function: the average pre-bronchodilator FEV increased by 21.3% (+680 ml) compared to baseline (p = 0,0006). Moreover, the improvement in morning PEF (+66,6 l/min) confirmed the benefit of benralizumab (p = 0,02). The improvement in respiratory function was significantly higher in patients with blood eosinophilia greater than 500 cells/μL and chronic rhinosinusitis with nasal polyps (CRSwNP). This study underlies a noticeable improvement in respiratory function, much higher than what has been observed in literature so far. This aspect, together with the others aforementioned, should be considered when choosing a treatment option in the context of precision medicine.
严重嗜酸粒细胞性哮喘是一种复杂的疾病,人们为了充分了解其发病机制付出了巨大的努力。支气管重塑和肺功能丧失是哮喘的重要特征,但它们的关键方面尚不完全清楚,特别是生物药物可能对其产生的影响。白细胞介素-5(IL-5)是参与嗜酸粒细胞性哮喘病理生理学的关键细胞因子之一,它与其他 2 型细胞因子和趋化因子一起,在嗜酸性粒细胞向气道的发育、迁移和持续存在中发挥着非常重要的作用,如 eotaxin-2 和 3、胸腺基质淋巴细胞生成素(TSLP)、IL-33 以及 IL-4 和 IL-13。已经开发出几种针对这种细胞因子(美泊利珠单抗、瑞利珠单抗)或其受体(贝那利珠单抗)的单克隆抗体。关于接受贝那利珠单抗治疗的患者呼吸功能改善的数据很少,而且部分相互矛盾。真实世界研究可能在阐明这一重要方面发挥关键作用。本回顾性观察性真实世界研究的目的是评估贝那利珠单抗在意大利雷焦艾米利亚地方卫生局肺病科治疗的 20 例严重难治性哮喘(SRA)患者中,治疗 6 个月后对肺功能改善、加重率、口服皮质类固醇(OCS)减少和哮喘控制问卷(ACQ)评分的影响。贝那利珠单抗的附加治疗使 20 例患者中的 19 例完全停用 OCS。值得注意的是,中度/重度加重的次数明显减少(p<0.0001);ACQ 评分也有所改善(p<0.0001)。最相关的数据涉及呼吸功能:与基线相比,支气管扩张前 FEV 平均增加 21.3%(+680ml)(p=0.0006)。此外,晨峰呼气流速(PEF)的改善(+66.6l/min)证实了贝那利珠单抗的益处(p=0.02)。血液嗜酸性粒细胞大于 500 细胞/μL 和慢性鼻-鼻窦炎伴鼻息肉(CRSwNP)的患者,其呼吸功能的改善更为显著。这项研究表明呼吸功能显著改善,远高于目前文献中的观察结果。在精准医学的背景下,在选择治疗方案时,应考虑到这一方面,以及上述其他方面。