Guy's Severe Asthma Centre, Guy's and St Thomas' Hospitals, London, England; Asthma UK Centre, King's College London, London, England.
Guy's Severe Asthma Centre, Guy's and St Thomas' Hospitals, London, England.
Chest. 2021 Feb;159(2):496-506. doi: 10.1016/j.chest.2020.08.2083. Epub 2020 Aug 31.
Benralizumab is an IL5-receptor monoclonal antibody licensed for the treatment of severe eosinophilic asthma (SEA). It has demonstrated efficacy in clinical trials in reducing asthma exacerbation rates and maintenance oral corticosteroids (mOCSs).
What is the real-world effectiveness of benralizumab and what baseline characteristics are associated with response to therapy?
We assessed outcomes in all SEA patients who began benralizumab treatment at our specialist center. At each dosing visit, exacerbation history, mOCS dose, spirometry, and Asthma Control Questionnaire (ACQ6) and Mini-Asthma Quality of Life Questionnaire (mAQLQ) scores were recorded. Response to treatment was defined as a reduction of ≥ 50% in annualized exacerbation rate (AER) or in mOCS dose after 48 weeks of treatment. Super response was defined as zero exacerbations and no mOCSs for asthma.
One hundred thirty patients were included in the analysis. At 48 weeks, a 72.8% reduction in AER was noted, from 4.92 ± 3.35 per year in the year preceding biologic treatment to 1.34 ± 1.71 per year (P < .001), including 57 patients (43.8%) who were exacerbation-free with benralizumab. In those receiving mOCSs (n = 74 [56.9%]), the median daily prednisolone dose fell from 10 mg (interquartile range, 5-20 mg) to 0 mg (interquartile range, 0-5 mg; P < .001), and 38 of 74 patients (51.4%) were able to discontinue mOCS therapy. Clinically and statistically significant improvements were found in ACQ6 scores, mAQLQ scores, and FEV. Overall, 51 patients (39%) met the super responder definition and 112 patients (86%) met the responder definition. The optimal regression model of super responders vs other responders included baseline characteristics associated with a strongly eosinophilic phenotype and less severe disease. Eighteen patients (13.8%) were nonresponders to benralizumab. Evidence of chronic airway infection was observed in 6 of 18 patients, and an increase in the blood eosinophil count consistent with the development of anti-drug antibodies was observed in 5 of 18 patients.
In a large real-world SEA cohort, benralizumab led to significant improvements in all clinical outcome measures. A lack of response was seen in a minority of patients and should be a focus for future investigation.
贝那鲁肽是一种 IL5 受体单克隆抗体，已获许可用于治疗严重嗜酸性粒细胞性哮喘（SEA）。临床试验表明，该药可降低哮喘恶化率和维持口服皮质类固醇（mOCS）的使用。
贝那鲁肽的真实世界疗效如何？哪些基线特征与治疗反应相关？
我们评估了在我们的专科中心开始接受贝那鲁肽治疗的所有 SEA 患者的结局。在每次给药就诊时，记录哮喘恶化史、mOCS 剂量、肺功能、哮喘控制问卷（ACQ6）和迷你哮喘生活质量问卷（mAQLQ）评分。治疗反应定义为治疗 48 周后，年化哮喘恶化率（AER）或 mOCS 剂量降低≥50%。超级反应定义为哮喘零恶化且无 mOCS。
130 例患者纳入分析。48 周时，AER 降低 72.8%，从生物治疗前 1 年的 4.92 ± 3.35 次/年降至 1.34 ± 1.71 次/年（P<.001），包括 57 例（43.8%）患者使用贝那鲁肽后无哮喘恶化。在接受 mOCS 治疗的患者中（n=74[56.9%]），中位泼尼松龙日剂量从 10 mg（四分位距，5-20 mg）降至 0 mg（四分位距，0-5 mg；P<.001），74 例患者中有 38 例（51.4%）能够停用 mOCS 治疗。ACQ6 评分、mAQLQ 评分和 FEV 均有临床和统计学意义的显著改善。总体而言，51 例（39%）患者符合超级反应者定义，112 例（86%）患者符合反应者定义。超级反应者与其他反应者的最佳回归模型包括与强嗜酸性粒细胞表型和较轻疾病相关的基线特征。18 例（13.8%）患者对贝那鲁肽无反应。18 例患者中有 6 例存在慢性气道感染证据，18 例患者中有 5 例观察到血嗜酸性粒细胞计数增加，与抗药物抗体的发展一致。
在一项大型 SEA 真实世界队列研究中，贝那鲁肽可显著改善所有临床结局指标。少数患者无反应，应作为未来研究的重点。
