重症哮喘患者Benralizumab增强反应的预测因素：SIROCCO和CALIMA研究的汇总分析
2017/09/29
摘要
背景：Benralizumab是一种抗嗜酸性，抗白细胞介素-5受体α单克隆抗体，已被证明可显著降低哮喘急性发作并改善严重不受控制哮喘患者的肺功能。我们进一步探讨了Benralizumab对不同基线血液嗜酸性粒细胞阈值和发作史的影响。
方法：本研究是对随机，双盲，安慰剂对照的SIROCCO（NCT01928771）和CALIMA（NCT01914757）3期研究的结果进行汇总分析。在这些研究中，严重不受控制的哮喘患者被随机分配（1：1：1），接受皮下给予benralizumab 30 mg，每4周或每8周（前3次剂量每4周）或安慰剂，每4周。主要终点是年度发作率（AER）与安慰剂的比例，通过基线嗜酸性粒细胞计数（≥0，≥150，≥300或≥450细胞/μL）以及治疗前每年加重次数（两次或三次以上）分析。分析是按照意向治疗原则进行的。
结果:2295例患者中，756例每4周接受benralizumab治疗， 762例每8周接受benralizumab治疗，安慰剂组777例。在接受安慰剂的患者中，基线血液嗜酸性粒细胞计数至少为0个细胞/μL的患者的AER为1·16（95％CI 1·05-1·28），而每8周接受benralizumab的患者为0.75（0·66-0·84）（速率比0·64，0·55-0·75; p <0·0001）。每4周接受benralizumab治疗嗜酸性粒细胞计数为0或更多细胞/μL的患者，AER为0·73（0·65-0·82）;速率与安慰剂的比值为0.63（0·54-0·74; p <0.0001）。急性发作率降低的程度随着血液嗜酸性粒细胞阈值和4周、8周benralizumab患者发作史次数的增加而增加。与安慰剂相比，benralizumab能明显改善高血嗜酸粒细胞阈值和频繁发作病史患者的AER。
结论：这些结果将有助于指导临床医生决定是否使用benralizumab治疗严重，不受控制的嗜酸粒细胞性哮喘患者。
Predictors of enhanced response with benralizumab for patients with severe asthma: pooled analysis of the SIROCCO and CALIMA studies.
FitzGerald JM1, Bleecker ER2, Menzies-Gow A3, Zangrilli JG4, Hirsch I4, Metcalfe P5, Newbold P6, Goldman M4.
Abstract
INTRODUCTION:Benralizumab is an anti-eosinophilic, anti-interleukin-5 receptor α monoclonal antibody that has been shown to significantly reduce asthma exacerbations and improve lung function for patients with severe, uncontrolled asthma. We further explored the efficacy of benralizumab for patients with different baseline blood eosinophil thresholds and exacerbation histories.
METHODS:This study is a pooled analysis of the results from the randomised, double-blind, placebo-controlled SIROCCO (NCT01928771) and CALIMA (NCT01914757) phase 3 studies. In these studies, patients with severe, uncontrolled asthma were randomly assigned (1:1:1) to receive subcutaneous benralizumab 30 mg, either every 4 weeks or every 8 weeks (with first three doses given every 4 weeks), or placebo every 4 weeks. The primary endpoint was annual exacerbation rate (AER) ratio versus placebo, analysed by baseline eosinophil counts (≥0, ≥150, ≥300, or ≥450 cells per μL) and by number of exacerbations (two vs three or more) during the year before enrolment. The analyses were done in accordance with the intention-to-treat principle.
RESULTS:Of 2295 patients, 756 received benralizumab every 4 weeks, 762 received benralizumab every 8 weeks, and 777 patients received placebo. AER among patients with baseline blood eosinophil counts of at least 0 cells per μL was 1·16 (95% CI 1·05-1·28) in patients who received placebo versus 0·75 (0·66-0·84) in patients who received benralizumab every 8 weeks (rate ratio 0·64, 0·55-0·75; p<0·0001). In patients who received benralizumab every 4 weeks who had eosinophil counts of 0 or more cells per μL, AER was 0·73 (0·65-0·82); rate ratio versus placebo was 0·63 (0·54-0·74; p<0·0001). The extent to which exacerbation rates were reduced increased with increasing blood eosinophil thresholds and with greater exacerbation history in patients in the 4-weekly and 8-weekly benralizumab groups. Greater improvements in AER were seen with benralizumab compared with placebo for patients with a combination of high blood eosinophil thresholds and a history of more frequent exacerbations.
CONCLUSIONS:These results will help to guide clinicians when they are deciding whether to use benralizumab to treat patients with severe, uncontrolled, eosinophilic asthma.
背景：Benralizumab是一种抗嗜酸性，抗白细胞介素-5受体α单克隆抗体，已被证明可显著降低哮喘急性发作并改善严重不受控制哮喘患者的肺功能。我们进一步探讨了Benralizumab对不同基线血液嗜酸性粒细胞阈值和发作史的影响。
方法：本研究是对随机，双盲，安慰剂对照的SIROCCO（NCT01928771）和CALIMA（NCT01914757）3期研究的结果进行汇总分析。在这些研究中，严重不受控制的哮喘患者被随机分配（1：1：1），接受皮下给予benralizumab 30 mg，每4周或每8周（前3次剂量每4周）或安慰剂，每4周。主要终点是年度发作率（AER）与安慰剂的比例，通过基线嗜酸性粒细胞计数（≥0，≥150，≥300或≥450细胞/μL）以及治疗前每年加重次数（两次或三次以上）分析。分析是按照意向治疗原则进行的。
结果:2295例患者中，756例每4周接受benralizumab治疗， 762例每8周接受benralizumab治疗，安慰剂组777例。在接受安慰剂的患者中，基线血液嗜酸性粒细胞计数至少为0个细胞/μL的患者的AER为1·16（95％CI 1·05-1·28），而每8周接受benralizumab的患者为0.75（0·66-0·84）（速率比0·64，0·55-0·75; p <0·0001）。每4周接受benralizumab治疗嗜酸性粒细胞计数为0或更多细胞/μL的患者，AER为0·73（0·65-0·82）;速率与安慰剂的比值为0.63（0·54-0·74; p <0.0001）。急性发作率降低的程度随着血液嗜酸性粒细胞阈值和4周、8周benralizumab患者发作史次数的增加而增加。与安慰剂相比，benralizumab能明显改善高血嗜酸粒细胞阈值和频繁发作病史患者的AER。
结论：这些结果将有助于指导临床医生决定是否使用benralizumab治疗严重，不受控制的嗜酸粒细胞性哮喘患者。
(中日友好医院呼吸与危重症医学科 王瑞茵 摘译 林江涛 审校)
(Lancet Respir Med. 2017 Sep 8. pii: S2213-2600(17)30344-2. doi: 10.1016/S2213-2600(17)30344-2. [Epub ahead of print] )
(Lancet Respir Med. 2017 Sep 8. pii: S2213-2600(17)30344-2. doi: 10.1016/S2213-2600(17)30344-2. [Epub ahead of print] )
Predictors of enhanced response with benralizumab for patients with severe asthma: pooled analysis of the SIROCCO and CALIMA studies.
FitzGerald JM1, Bleecker ER2, Menzies-Gow A3, Zangrilli JG4, Hirsch I4, Metcalfe P5, Newbold P6, Goldman M4.
Abstract
INTRODUCTION:Benralizumab is an anti-eosinophilic, anti-interleukin-5 receptor α monoclonal antibody that has been shown to significantly reduce asthma exacerbations and improve lung function for patients with severe, uncontrolled asthma. We further explored the efficacy of benralizumab for patients with different baseline blood eosinophil thresholds and exacerbation histories.
METHODS:This study is a pooled analysis of the results from the randomised, double-blind, placebo-controlled SIROCCO (NCT01928771) and CALIMA (NCT01914757) phase 3 studies. In these studies, patients with severe, uncontrolled asthma were randomly assigned (1:1:1) to receive subcutaneous benralizumab 30 mg, either every 4 weeks or every 8 weeks (with first three doses given every 4 weeks), or placebo every 4 weeks. The primary endpoint was annual exacerbation rate (AER) ratio versus placebo, analysed by baseline eosinophil counts (≥0, ≥150, ≥300, or ≥450 cells per μL) and by number of exacerbations (two vs three or more) during the year before enrolment. The analyses were done in accordance with the intention-to-treat principle.
RESULTS:Of 2295 patients, 756 received benralizumab every 4 weeks, 762 received benralizumab every 8 weeks, and 777 patients received placebo. AER among patients with baseline blood eosinophil counts of at least 0 cells per μL was 1·16 (95% CI 1·05-1·28) in patients who received placebo versus 0·75 (0·66-0·84) in patients who received benralizumab every 8 weeks (rate ratio 0·64, 0·55-0·75; p<0·0001). In patients who received benralizumab every 4 weeks who had eosinophil counts of 0 or more cells per μL, AER was 0·73 (0·65-0·82); rate ratio versus placebo was 0·63 (0·54-0·74; p<0·0001). The extent to which exacerbation rates were reduced increased with increasing blood eosinophil thresholds and with greater exacerbation history in patients in the 4-weekly and 8-weekly benralizumab groups. Greater improvements in AER were seen with benralizumab compared with placebo for patients with a combination of high blood eosinophil thresholds and a history of more frequent exacerbations.
CONCLUSIONS:These results will help to guide clinicians when they are deciding whether to use benralizumab to treat patients with severe, uncontrolled, eosinophilic asthma.
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