每年两次Depemokimab治疗嗜酸性表型的重度哮喘患者
2024/09/29
摘要
背景：Depemokimab是一种超长效生物疗法，对白细胞介素-5的结合亲和力增强，可能实现有效的6个月给药间隔。
方法：在这些3A期、随机、安慰剂对照的重复试验中，我们评估了Depemokimab对重度哮喘患者的疗效和安全性，这些患者具有嗜酸性粒细胞计数高（过去12个月内每微升≥300个细胞，或筛查时每微升≥150个细胞）和急性发作史，尽管接受了中剂量或高剂量的吸入性糖皮质激素。患者以2:1的比例随机分配，在第0周和第26周接受depemokimab（皮下注射100mg剂量）或安慰剂治疗，并接受标准护理。主要终点是52周时的年恶化率。次要终点以分层方式进行分析，以调整多样性，包括圣乔治呼吸问卷（SGRQ）评分与基线的变化、1秒内的用力呼气量和52周时的哮喘症状报告。
结果：在两项试验中，792名患者接受了随机分组，762名患者被纳入全面分析；502名患者被分配接受depemokimab治疗，260名患者接受安慰剂治疗。在SWIFT-1中，depemokimab的年化恶化率为0.46（（95%置信区间[CI]），0.36至0.58），安慰剂为1.11（95%CI，0.86至1.43）（比率比，0.42；95%CI，0.30至0.59；P<0.001）；在SWIFT-2中depemokimab的年化恶化率为0.56（95%CI，0.44至0.70），安慰剂为为1.08（95%CI,0.83至1.41）(比率比, 0.52; 95% CI, 0.36 to 0.73; P<0.001)。在两项试验中，SGRQ评分与基线相比的变化没有显著的组间差异，因此没有对后续的次要终点进行统计推断。在两项试验中，两组出现任何不良事件的患者比例相似。
结论：Depemokimab降低了具有嗜酸性表型的重度哮喘患者的年恶化率。（由葛兰素史克资助；SWIFT-1和SWIFT-2 ClinicalTrials.gov编号，NCT04719832和NCT04718103。）。
Twice-Yearly Depemokimab in Severe Asthma with an Eosinophilic Phenotype
David J Jackson 1, Michael E Wechsler, Daniel J Jackson, David Bernstein, Stephanie Korn, Paul E Pfeffer, Ruchong Chen, Junpei Saito, Gustavo de Luíz Martinez, Lucyna Dymek, Loretta Jacques, Nicholas Bird, Stein Schalkwijk, Douglas Smith, Peter Howarth, Ian D Pavord; SWIFT-1 and SWIFT-2 Investigators
Abstract
Background: Depemokimab is an ultra-long-acting biologic therapy with enhanced binding affinity for interleukin-5 that may enable effective 6-month dosing intervals.
Methods: In these phase 3A, randomized, placebo-controlled replicate trials, we evaluated the efficacy and safety of depemokimab in patients with severe asthma and an eosinophilic phenotype characterized by a high eosinophil count (≥300 cells per microliter in the previous 12 months or ≥150 cells per microliter at screening) and a history of exacerbations despite the receipt of medium- or high-dose inhaled glucocorticoids. Patients were randomly assigned in a 2:1 ratio to receive either depemokimab (at a dose of 100 mg subcutaneously) or placebo at weeks 0 and 26, plus standard care. The primary end point was the annualized rate of exacerbations at 52 weeks. Secondary end points, which were analyzed in a hierarchical manner to adjust for multiplicity, included the change from baseline in the score on the St. George's Respiratory Questionnaire (SGRQ), the forced expiratory volume in 1 second, and asthma symptom reports at 52 weeks.
Results: Across the two trials, 792 patients underwent randomization and 762 were included in the full analysis; 502 were assigned to receive depemokimab and 260 to receive placebo. The annualized rate of exacerbations was 0.46 (95% confidence interval [CI]), 0.36 to 0.58) with depemokimab and 1.11 (95% CI, 0.86 to 1.43) with placebo (rate ratio, 0.42; 95% CI, 0.30 to 0.59; P<0.001) in SWIFT-1 and 0.56 (95% CI, 0.44 to 0.70) with depemokimab and 1.08 (95% CI, 0.83 to 1.41) with placebo (rate ratio, 0.52; 95% CI, 0.36 to 0.73; P<0.001) in SWIFT-2. No significant between-group difference in the change from baseline in the SGRQ score was observed in either trial, so no statistical inference was drawn on subsequent secondary end points. The proportion of patients with any adverse event was similar in the two groups in both trials.
Conclusions: Depemokimab reduced the annualized rate of exacerbations among patients with severe asthma with an eosinophilic phenotype. (Funded by GSK; SWIFT-1 and SWIFT-2 ClinicalTrials.gov numbers, NCT04719832 and NCT04718103.).
背景：Depemokimab是一种超长效生物疗法，对白细胞介素-5的结合亲和力增强，可能实现有效的6个月给药间隔。
方法：在这些3A期、随机、安慰剂对照的重复试验中，我们评估了Depemokimab对重度哮喘患者的疗效和安全性，这些患者具有嗜酸性粒细胞计数高（过去12个月内每微升≥300个细胞，或筛查时每微升≥150个细胞）和急性发作史，尽管接受了中剂量或高剂量的吸入性糖皮质激素。患者以2:1的比例随机分配，在第0周和第26周接受depemokimab（皮下注射100mg剂量）或安慰剂治疗，并接受标准护理。主要终点是52周时的年恶化率。次要终点以分层方式进行分析，以调整多样性，包括圣乔治呼吸问卷（SGRQ）评分与基线的变化、1秒内的用力呼气量和52周时的哮喘症状报告。
结果：在两项试验中，792名患者接受了随机分组，762名患者被纳入全面分析；502名患者被分配接受depemokimab治疗，260名患者接受安慰剂治疗。在SWIFT-1中，depemokimab的年化恶化率为0.46（（95%置信区间[CI]），0.36至0.58），安慰剂为1.11（95%CI，0.86至1.43）（比率比，0.42；95%CI，0.30至0.59；P<0.001）；在SWIFT-2中depemokimab的年化恶化率为0.56（95%CI，0.44至0.70），安慰剂为为1.08（95%CI,0.83至1.41）(比率比, 0.52; 95% CI, 0.36 to 0.73; P<0.001)。在两项试验中，SGRQ评分与基线相比的变化没有显著的组间差异，因此没有对后续的次要终点进行统计推断。在两项试验中，两组出现任何不良事件的患者比例相似。
结论：Depemokimab降低了具有嗜酸性表型的重度哮喘患者的年恶化率。（由葛兰素史克资助；SWIFT-1和SWIFT-2 ClinicalTrials.gov编号，NCT04719832和NCT04718103。）。
(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)
(N Engl J Med. 2024 Sep 9. doi: 10.1056/NEJMoa2406673.)
(N Engl J Med. 2024 Sep 9. doi: 10.1056/NEJMoa2406673.)
Twice-Yearly Depemokimab in Severe Asthma with an Eosinophilic Phenotype
David J Jackson 1, Michael E Wechsler, Daniel J Jackson, David Bernstein, Stephanie Korn, Paul E Pfeffer, Ruchong Chen, Junpei Saito, Gustavo de Luíz Martinez, Lucyna Dymek, Loretta Jacques, Nicholas Bird, Stein Schalkwijk, Douglas Smith, Peter Howarth, Ian D Pavord; SWIFT-1 and SWIFT-2 Investigators
Abstract
Background: Depemokimab is an ultra-long-acting biologic therapy with enhanced binding affinity for interleukin-5 that may enable effective 6-month dosing intervals.
Methods: In these phase 3A, randomized, placebo-controlled replicate trials, we evaluated the efficacy and safety of depemokimab in patients with severe asthma and an eosinophilic phenotype characterized by a high eosinophil count (≥300 cells per microliter in the previous 12 months or ≥150 cells per microliter at screening) and a history of exacerbations despite the receipt of medium- or high-dose inhaled glucocorticoids. Patients were randomly assigned in a 2:1 ratio to receive either depemokimab (at a dose of 100 mg subcutaneously) or placebo at weeks 0 and 26, plus standard care. The primary end point was the annualized rate of exacerbations at 52 weeks. Secondary end points, which were analyzed in a hierarchical manner to adjust for multiplicity, included the change from baseline in the score on the St. George's Respiratory Questionnaire (SGRQ), the forced expiratory volume in 1 second, and asthma symptom reports at 52 weeks.
Results: Across the two trials, 792 patients underwent randomization and 762 were included in the full analysis; 502 were assigned to receive depemokimab and 260 to receive placebo. The annualized rate of exacerbations was 0.46 (95% confidence interval [CI]), 0.36 to 0.58) with depemokimab and 1.11 (95% CI, 0.86 to 1.43) with placebo (rate ratio, 0.42; 95% CI, 0.30 to 0.59; P<0.001) in SWIFT-1 and 0.56 (95% CI, 0.44 to 0.70) with depemokimab and 1.08 (95% CI, 0.83 to 1.41) with placebo (rate ratio, 0.52; 95% CI, 0.36 to 0.73; P<0.001) in SWIFT-2. No significant between-group difference in the change from baseline in the SGRQ score was observed in either trial, so no statistical inference was drawn on subsequent secondary end points. The proportion of patients with any adverse event was similar in the two groups in both trials.
Conclusions: Depemokimab reduced the annualized rate of exacerbations among patients with severe asthma with an eosinophilic phenotype. (Funded by GSK; SWIFT-1 and SWIFT-2 ClinicalTrials.gov numbers, NCT04719832 and NCT04718103.).
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