从美泊利单抗/本瑞利珠单抗转换为每年2次德莫奇单抗治疗重度哮喘：一项多中心、随机、双盲IIIA期临床试验（NIMBLE）
2026/04/02
摘要
背景：德莫奇单抗（depemokimab）是首款超长效生物制剂，具有高白介素-5结合亲和力、高效价及延长的半衰期，可实现每年给药2次。
目的：本研究旨在探讨已接受靶向白介素-5或其受体的短效生物制剂治疗且病情控制良好的重度哮喘患者，转换为德莫奇单抗治疗的有效性与安全性。
方法：NIMBLE研究（NCT04718389）为一项多中心、随机、双盲、双模拟、平行分组的IIIA期非劣效性研究。入组患者≥12岁，确诊哮喘，且接受美泊利单抗100 mg皮下注射每 4 周 1 次或本瑞利珠单抗30mg皮下注射每8周1次治疗≥12个月并获得明确临床获益。患者按1:1比例随机分配，分别接受德莫奇单抗100 mg 皮下注射每26周1次，或维持原生物制剂（美泊利单抗或本瑞利珠单抗）治疗。主要终点为52周内临床显著急性加重的年化发生率，预设非劣效界值为1.28。安全性终点包含不良事件。
结果：52周内，德莫奇单抗组（n=848）临床显著急性加重年发生率（95%置信区间）为0.57（0.50～0.64），阳性对照组（n=839）为0.49（0.43～0.55）；发生率比（95%置信区间）为1.16（0.98~1.38）。因 95%置信区间上限超过1.28，未达到非劣效性标准。两组多数患者均未发生临床显著急性加重。研究期间，患者健康相关生活质量、哮喘控制水平及肺功能结局均保持稳定。两组不良事件发生率相当。
结论：尽管未达到统计学非劣效性标准，但两组患者急性加重发生率均较低，且症状控制与肺功能均得以维持。本项首个重度哮喘随机对照转换研究提示，接受美泊利单抗或本瑞利珠单抗治疗的重度哮喘患者，可安全转换为每年给药2次的德莫奇单抗。
Switching to twice-yearly depemokimab from mepolizumab/benralizumab in severe asthma: A multicenter, randomized, double-blind, Phase 3A Clinical Trial (NIMBLE). Chupp G, Nagase H, Skowasch D, Devouassoux G, Côté A, Jackson DJ, Jackson DJ, Wechsler ME, Imber V, McGinniss JE, K SO, Howarth P, Pavord ID; NIMBLE Study Investigators.
Abstract
BACKGROUND: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.
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.
CONCLUSION: 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.
背景：德莫奇单抗（depemokimab）是首款超长效生物制剂，具有高白介素-5结合亲和力、高效价及延长的半衰期，可实现每年给药2次。
目的：本研究旨在探讨已接受靶向白介素-5或其受体的短效生物制剂治疗且病情控制良好的重度哮喘患者，转换为德莫奇单抗治疗的有效性与安全性。
方法：NIMBLE研究（NCT04718389）为一项多中心、随机、双盲、双模拟、平行分组的IIIA期非劣效性研究。入组患者≥12岁，确诊哮喘，且接受美泊利单抗100 mg皮下注射每 4 周 1 次或本瑞利珠单抗30mg皮下注射每8周1次治疗≥12个月并获得明确临床获益。患者按1:1比例随机分配，分别接受德莫奇单抗100 mg 皮下注射每26周1次，或维持原生物制剂（美泊利单抗或本瑞利珠单抗）治疗。主要终点为52周内临床显著急性加重的年化发生率，预设非劣效界值为1.28。安全性终点包含不良事件。
结果：52周内，德莫奇单抗组（n=848）临床显著急性加重年发生率（95%置信区间）为0.57（0.50～0.64），阳性对照组（n=839）为0.49（0.43～0.55）；发生率比（95%置信区间）为1.16（0.98~1.38）。因 95%置信区间上限超过1.28，未达到非劣效性标准。两组多数患者均未发生临床显著急性加重。研究期间，患者健康相关生活质量、哮喘控制水平及肺功能结局均保持稳定。两组不良事件发生率相当。
结论：尽管未达到统计学非劣效性标准，但两组患者急性加重发生率均较低，且症状控制与肺功能均得以维持。本项首个重度哮喘随机对照转换研究提示，接受美泊利单抗或本瑞利珠单抗治疗的重度哮喘患者，可安全转换为每年给药2次的德莫奇单抗。
（中日友好医院呼吸与危重症医学科 张婧媛 摘译 林江涛 审校）
（ Am J Respir Crit Care Med. 2026 Feb 11:aamag031. doi: 10.1093/ajrccm/aamag031.）
（ Am J Respir Crit Care Med. 2026 Feb 11:aamag031. doi: 10.1093/ajrccm/aamag031.）
Switching to twice-yearly depemokimab from mepolizumab/benralizumab in severe asthma: A multicenter, randomized, double-blind, Phase 3A Clinical Trial (NIMBLE). Chupp G, Nagase H, Skowasch D, Devouassoux G, Côté A, Jackson DJ, Jackson DJ, Wechsler ME, Imber V, McGinniss JE, K SO, Howarth P, Pavord ID; NIMBLE Study Investigators.
Abstract
BACKGROUND: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.
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.
CONCLUSION: 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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