重度哮喘患者从美泊利珠单抗/贝那利珠单抗转为每年两次的德佩莫单抗：一项多中心、随机、双盲、3A期临床试验（NIMBLE）
2026/03/04
摘要：
基本原理：德佩莫单抗是第一种超长效生物制剂，具有高白介素-5结合亲和力，高效，半衰期延长，可以每年两次给药。
目的：研究已接受针对白细胞介素-5或其受体的短效生物疗法治疗并对其有反应的重度哮喘患者改用德佩莫单抗的疗效和安全性。
方法：NIMBLE （NCT04718389）是一项多中心、随机、双盲、双哑、平行组、3A期非劣效性研究。参与者年龄≥12岁，患有哮喘，并且美泊利珠单抗每4周皮下注射100 mg或贝那利珠单抗每8周皮下注射30 mg，临床获益≥12个月。参与者按1:1随机分配，每26周皮下注射德佩莫单抗 100 mg，或维持其先前的生物制剂（美泊利珠单抗或贝那利珠单抗）。主要终点是52周内临床显著恶化的年化率，预定义的非劣效性边际设定为1.28。安全终点包括不良事件。
测量结果和主要结果：52周内临床显著加重的年化率（95%置信区间）在德佩莫单抗组（n = 848）为0.57(0.50至0.64），在对照组（n = 839）为0.49(0.43至0.55）；比率比（95%置信区间）为1.16[0.98 ~ 1.38]）。由于95%置信区间的上界超过1.28，因此不满足非劣效性。两个治疗组的大多数参与者都没有出现明显的临床恶化。在整个研究过程中，健康相关的生活质量、哮喘控制和肺功能结果都是稳定的。治疗组间不良事件具有可比性。
结论：两组患者均未达到统计学上的非劣效性，但病情加重率均较低，且均能维持症状控制和肺功能。这是首个针对重度哮喘的随机对照切换试验，表明使用美泊利珠单抗或贝那利珠单抗的重度哮喘患者可以安全地切换到每年两次的德佩莫单抗。
Switching to twice-yearly depemokimab from mepolizumab/benralizumab in severe asthma: A multicenter, randomized, double-blind, Phase 3A Clinical Trial (NIMBLE)
Geoffrey Chupp, Hiroyuki Nagase, Dirk Skowasch, Gilles Devouassoux, Andréanne Côté, Daniel J Jackson, David J Jackson, Michael E Wechsler, Varsha Imber, John E McGinniss Sherine O K, Peter Howarth, Ian D Pavord; NIMBLE Study Investigators
Abstract
Rationale: Depemokimab is the first ultra-long-acting biologic with high interleukin-5 binding affinity, high potency, and an extended half-life enabling twice-yearly dosing.
Objectives: Investigate the efficacy and safety of switching to depemokimab in participants with severe asthma already managed with and responsive to short-acting biologic therapies targeting interleukin-5 or its receptor.
Methods: NIMBLE (NCT04718389) was a multicenter, randomized, double-blind, double-dummy, parallel-group, Phase 3A non-inferiority study. Participants were ≥12 years old with asthma and documented clinical benefit on mepolizumab 100 mg subcutaneously every 4 weeks or benralizumab 30 mg subcutaneously every 8 weeks for ≥12 months. Participants were randomized 1:1 to depemokimab 100 mg subcutaneously every 26 weeks or maintained on their prior biologic (mepolizumab or benralizumab). The primary endpoint was annualized rate of clinically significant exacerbations over 52 weeks, with predefined non-inferiority margin set at 1.28. Safety endpoints included adverse events.
Measurements and main results: Annualized rates (95% confidence intervals) of clinically significant exacerbations over 52 weeks were 0.57 (0.50 to 0.64) with depemokimab (n = 848) and 0.49 (0.43 to 0.55) with active comparator (n = 839); rate ratio (95% confidence interval) was 1.16 [0.98 to 1.38]. Since the upper bound of the 95% confidence interval exceeded 1.28, non-inferiority was not met. Most participants in both treatment arms experienced no clinically significant exacerbations. Health-related quality of life, asthma control, and lung function outcomes were stable throughout the study. Adverse events were comparable between treatment groups.
Conclusions: While statistical non-inferiority was not met, exacerbation rates were low and symptom control/lung function were maintained in both groups. This first randomized, controlled switch trial in severe asthma suggests that participants with severe asthma on mepolizumab or benralizumab may safely switch to twice-yearly depemokimab.
基本原理：德佩莫单抗是第一种超长效生物制剂，具有高白介素-5结合亲和力，高效，半衰期延长，可以每年两次给药。
目的：研究已接受针对白细胞介素-5或其受体的短效生物疗法治疗并对其有反应的重度哮喘患者改用德佩莫单抗的疗效和安全性。
方法：NIMBLE （NCT04718389）是一项多中心、随机、双盲、双哑、平行组、3A期非劣效性研究。参与者年龄≥12岁，患有哮喘，并且美泊利珠单抗每4周皮下注射100 mg或贝那利珠单抗每8周皮下注射30 mg，临床获益≥12个月。参与者按1:1随机分配，每26周皮下注射德佩莫单抗 100 mg，或维持其先前的生物制剂（美泊利珠单抗或贝那利珠单抗）。主要终点是52周内临床显著恶化的年化率，预定义的非劣效性边际设定为1.28。安全终点包括不良事件。
测量结果和主要结果：52周内临床显著加重的年化率（95%置信区间）在德佩莫单抗组（n = 848）为0.57(0.50至0.64），在对照组（n = 839）为0.49(0.43至0.55）；比率比（95%置信区间）为1.16[0.98 ~ 1.38]）。由于95%置信区间的上界超过1.28，因此不满足非劣效性。两个治疗组的大多数参与者都没有出现明显的临床恶化。在整个研究过程中，健康相关的生活质量、哮喘控制和肺功能结果都是稳定的。治疗组间不良事件具有可比性。
结论：两组患者均未达到统计学上的非劣效性，但病情加重率均较低，且均能维持症状控制和肺功能。这是首个针对重度哮喘的随机对照切换试验，表明使用美泊利珠单抗或贝那利珠单抗的重度哮喘患者可以安全地切换到每年两次的德佩莫单抗。
（北京朝阳医院呼吸与危重症医学科 顾宪民 摘译 中日友好医院呼吸与危重症医学科 林江涛 审校）
（Am J Respir Crit Care Med. 2026 Feb 11:aamag031. doi: 10.1093/ajrccm/aamag031. Online ahead of print.）
（Am J Respir Crit Care Med. 2026 Feb 11:aamag031. doi: 10.1093/ajrccm/aamag031. Online ahead of print.）
Switching to twice-yearly depemokimab from mepolizumab/benralizumab in severe asthma: A multicenter, randomized, double-blind, Phase 3A Clinical Trial (NIMBLE)
Geoffrey Chupp, Hiroyuki Nagase, Dirk Skowasch, Gilles Devouassoux, Andréanne Côté, Daniel J Jackson, David J Jackson, Michael E Wechsler, Varsha Imber, John E McGinniss Sherine O K, Peter Howarth, Ian D Pavord; NIMBLE Study Investigators
Abstract
Rationale: Depemokimab is the first ultra-long-acting biologic with high interleukin-5 binding affinity, high potency, and an extended half-life enabling twice-yearly dosing.
Objectives: Investigate the efficacy and safety of switching to depemokimab in participants with severe asthma already managed with and responsive to short-acting biologic therapies targeting interleukin-5 or its receptor.
Methods: NIMBLE (NCT04718389) was a multicenter, randomized, double-blind, double-dummy, parallel-group, Phase 3A non-inferiority study. Participants were ≥12 years old with asthma and documented clinical benefit on mepolizumab 100 mg subcutaneously every 4 weeks or benralizumab 30 mg subcutaneously every 8 weeks for ≥12 months. Participants were randomized 1:1 to depemokimab 100 mg subcutaneously every 26 weeks or maintained on their prior biologic (mepolizumab or benralizumab). The primary endpoint was annualized rate of clinically significant exacerbations over 52 weeks, with predefined non-inferiority margin set at 1.28. Safety endpoints included adverse events.
Measurements and main results: Annualized rates (95% confidence intervals) of clinically significant exacerbations over 52 weeks were 0.57 (0.50 to 0.64) with depemokimab (n = 848) and 0.49 (0.43 to 0.55) with active comparator (n = 839); rate ratio (95% confidence interval) was 1.16 [0.98 to 1.38]. Since the upper bound of the 95% confidence interval exceeded 1.28, non-inferiority was not met. Most participants in both treatment arms experienced no clinically significant exacerbations. Health-related quality of life, asthma control, and lung function outcomes were stable throughout the study. Adverse events were comparable between treatment groups.
Conclusions: While statistical non-inferiority was not met, exacerbation rates were low and symptom control/lung function were maintained in both groups. This first randomized, controlled switch trial in severe asthma suggests that participants with severe asthma on mepolizumab or benralizumab may safely switch to twice-yearly depemokimab.
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