Benralizumab治疗严重嗜酸性哮喘的真实世界有效性
2020/09/18
摘要
背景：Benralizumab是一种IL5受体单克隆抗体，用于治疗严重嗜酸细胞性哮喘（SEA）。在临床试验中，它在降低哮喘恶化率和维持口服皮质类固醇（mOCS）方面已显示出有效性。
研究问题：我们的目的是评估Benralizumab的真实世界有效性，并确定与治疗反应相关的基线特征。
研究设计和方法：我们评估了在本专科中心使用Benralizumab的所有SEA患者的结果。每次给药访视时，记录病情加重史、mOCS剂量、肺活量测定、哮喘控制问卷（ACQ6）和哮喘生活质量问卷（mAQLQ）评分。治疗应答是指治疗48周后，年加重率（AER）或mOCS剂量减少≥50%。超级应答被定义为哮喘的零加重和无mOCS服用。
结果：130例患者纳入分析。在48周时，AER降低了72.8%，从生物治疗前一年的4.92±3.35下降到1.34±1.71（p<0.001），其中57名（43.8%）患者使用Benralizumab后没有加重。在接受mOCS治疗的患者中（n=74；56.9%），泼尼松龙的中位每日剂量从10mg（5-20）降至0mg（0-5）（p<0.001），38/74（51.4%）的患者停止服用糖皮质激素。ACQ6、mAQLQ和FEV1在临床和统计学上均有显著改善。总体而言，51（39%）符合超级应答者的定义，112（86%）符合应答者的定义。超级应答者与其他应答者相比最佳回归模型包括基线为强嗜酸性粒细胞表型和疾病严重程度较轻。无应答者18例（13.8%），其中有6/18的患者出现慢性呼吸道感染，5/18的耐药患者血液嗜酸性粒细胞计数增加。
解释：在大型真实世界SEA队列中，Benralizumab使所有临床结果指标都有显著改善。少数人缺乏反应，应成为今后研究的重点。
Real World Effectiveness of Benralizumab in Severe Eosinophilic Asthma
Joanne E Kavanagh, Andrew P Hearn, Jaideep Dhariwal, Gráinne d'Ancona, Abdel Douiri, Cris Roxas, Mariana Fernandes, Linda Green, Louise Thomson, Alexandra M Nanzer, Brian D Kent, David J Jackson
Abstract
Background: 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 (mOCS).
Research question: Our aim was to evaluate the real-world effectiveness of benralizumab and identify any baseline characteristics associated with response to therapy.
Study design: & Methods: We assessed outcomes in all SEA patients commenced on benralizumab at our specialist centre. At each dosing visit, exacerbation history, mOCS dose, spirometry, 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 annualised exacerbation rate (AER) or in mOCS dose after 48 weeks of treatment. Super-response was defined as zero exacerbations and no mOCS for asthma.
Results: 130 patients were included in the analysis. At 48 weeks there was a 72.8% reduction in AER, from 4.92±3.35 in the year preceding biologic treatment to 1.34±1.71 (p<0.001), including 57(43.8%) patients who were exacerbation-free on benralizumab. In those on mOCS (n=74; 56.9%), the median daily prednisolone dose fell from 10mg (5-20) to 0mg (0-5) (p<0.001), and 38/74(51.4%) were able to discontinue mOCS. There were clinically and statistically significant improvements in ACQ6, mAQLQ and FEV1. Overall, 51 (39%) met the super-responder definition, and 112(86%) the responder definition. The optimal regression model of super-responders versus other responders included baseline characteristics associated with a strongly eosinophilic phenotype and less severe disease. Eighteen (13.8%) patients were non-responders to benralizumab. Evidence of chronic airway infection was observed in 6/18 and an increase in the blood eosinophil count consistent with the development of anti-drug antibodies in 5/18.
Interpretation: 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 and should be a focus for future investigation.
背景：Benralizumab是一种IL5受体单克隆抗体，用于治疗严重嗜酸细胞性哮喘（SEA）。在临床试验中，它在降低哮喘恶化率和维持口服皮质类固醇（mOCS）方面已显示出有效性。
研究问题：我们的目的是评估Benralizumab的真实世界有效性，并确定与治疗反应相关的基线特征。
研究设计和方法：我们评估了在本专科中心使用Benralizumab的所有SEA患者的结果。每次给药访视时，记录病情加重史、mOCS剂量、肺活量测定、哮喘控制问卷（ACQ6）和哮喘生活质量问卷（mAQLQ）评分。治疗应答是指治疗48周后，年加重率（AER）或mOCS剂量减少≥50%。超级应答被定义为哮喘的零加重和无mOCS服用。
结果：130例患者纳入分析。在48周时，AER降低了72.8%，从生物治疗前一年的4.92±3.35下降到1.34±1.71（p<0.001），其中57名（43.8%）患者使用Benralizumab后没有加重。在接受mOCS治疗的患者中（n=74；56.9%），泼尼松龙的中位每日剂量从10mg（5-20）降至0mg（0-5）（p<0.001），38/74（51.4%）的患者停止服用糖皮质激素。ACQ6、mAQLQ和FEV1在临床和统计学上均有显著改善。总体而言，51（39%）符合超级应答者的定义，112（86%）符合应答者的定义。超级应答者与其他应答者相比最佳回归模型包括基线为强嗜酸性粒细胞表型和疾病严重程度较轻。无应答者18例（13.8%），其中有6/18的患者出现慢性呼吸道感染，5/18的耐药患者血液嗜酸性粒细胞计数增加。
解释：在大型真实世界SEA队列中，Benralizumab使所有临床结果指标都有显著改善。少数人缺乏反应，应成为今后研究的重点。
(中日友好医院呼吸与危重症医学科 李红雯 摘译 林江涛 审校)
(Chest. 2020 Aug 31;S0012-3692(20)34313-0. doi: 10.1016/j.chest.2020.08.2083.)
(Chest. 2020 Aug 31;S0012-3692(20)34313-0. doi: 10.1016/j.chest.2020.08.2083.)
Real World Effectiveness of Benralizumab in Severe Eosinophilic Asthma
Joanne E Kavanagh, Andrew P Hearn, Jaideep Dhariwal, Gráinne d'Ancona, Abdel Douiri, Cris Roxas, Mariana Fernandes, Linda Green, Louise Thomson, Alexandra M Nanzer, Brian D Kent, David J Jackson
Abstract
Background: 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 (mOCS).
Research question: Our aim was to evaluate the real-world effectiveness of benralizumab and identify any baseline characteristics associated with response to therapy.
Study design: & Methods: We assessed outcomes in all SEA patients commenced on benralizumab at our specialist centre. At each dosing visit, exacerbation history, mOCS dose, spirometry, 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 annualised exacerbation rate (AER) or in mOCS dose after 48 weeks of treatment. Super-response was defined as zero exacerbations and no mOCS for asthma.
Results: 130 patients were included in the analysis. At 48 weeks there was a 72.8% reduction in AER, from 4.92±3.35 in the year preceding biologic treatment to 1.34±1.71 (p<0.001), including 57(43.8%) patients who were exacerbation-free on benralizumab. In those on mOCS (n=74; 56.9%), the median daily prednisolone dose fell from 10mg (5-20) to 0mg (0-5) (p<0.001), and 38/74(51.4%) were able to discontinue mOCS. There were clinically and statistically significant improvements in ACQ6, mAQLQ and FEV1. Overall, 51 (39%) met the super-responder definition, and 112(86%) the responder definition. The optimal regression model of super-responders versus other responders included baseline characteristics associated with a strongly eosinophilic phenotype and less severe disease. Eighteen (13.8%) patients were non-responders to benralizumab. Evidence of chronic airway infection was observed in 6/18 and an increase in the blood eosinophil count consistent with the development of anti-drug antibodies in 5/18.
Interpretation: 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 and should be a focus for future investigation.
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