非控制性或口服皮质类固醇依赖性过敏性和非过敏性哮喘患者的度普利尤单抗疗效
2023/02/01
摘要
背景：2型细胞因子白介素（IL）-4/IL-5/IL-13在包括哮喘在内的2型疾病的发病机制中起着重要作用。度普利尤单抗是一种人单克隆抗体，它阻断IL-4/IL-13的共同受体成分，抑制信号传导。在2b期（P2B）（NCT01854047）和3期VENTURE（NCT02528214）中，度普利尤单抗降低了年化严重加重率（AER），改善了一秒钟内用力呼气量（FEV1），并且在未控制、中度至重度或口服皮质类固醇（OCS）依赖性重度哮喘患者中通常耐受良好。
目的：对按过敏状态分层的P2B和VENTURE患者的度普利尤单抗疗效与安慰剂疗效进行事后评估。
方法：过敏性哮喘定义为基线时血清总免疫球蛋白E（IgE）≥30 IU/mL和≥1个常年性空气变应原特异性IgE≥0.35 kU/L。评估AER、支气管扩张前（BD）FEV1、FEV1/用力肺活量（FVC）比值、哮喘控制（5项哮喘控制问卷[ACQ-5]）、健康相关生活质量（HRQoL；哮喘生活质量问卷[AQLQ]）、2型生物标志物、特异性IgE和OCS降低（仅限VENTURE）。
结果：在过敏性哮喘患者中，与安慰剂组相比，每2周一次的度普利尤单抗（P2B:合并200/300mg；VENTURE:300mg）可降低AER（P2B:-60%，P<0.01；VENTURE：-72%，P<0.001），并且在P2B组，增加了BD前FEV1（P<0.01）和FEV1/FVC（P<0.05）。在这两项研究中，度普利尤单抗改善了哮喘控制和HRQoL，并降低了大多数2型生物标志物。度普利尤单抗显著减少了VENTURE中OCS的使用。在没有过敏性哮喘证据的患者中也观察到了类似的益处。
结论：在有或无过敏性哮喘证据的患者中，度普利尤单抗显著降低AER，改善肺功能、哮喘控制和HRQoL。
Dupilumab Efficacy in Patients with Uncontrolled or Oral Corticosteroid-Dependent Allergic and Non-allergic Asthma
Guy Brusselle, Santiago Quirce, Alberto Papi, Piotr Kuna, Bradley E Chipps, Nicola A Hanania, Michael Blaiss, Jérôme Msihid, Juby A Jacob-Nara, Yamo Deniz, Paul J Rowe, Rebecca Gall, Benjamin Ortiz, Michel Djandji, Amr Radwan
Abstract
Background: Type 2 cytokines interleukin (IL)-4/IL-5/IL-13 play an important role in pathogenesis of type 2 conditions, including asthma. Dupilumab, a human monoclonal antibody, blocks the shared receptor component for IL-4/IL-13, inhibiting signaling. In phase 2b (P2B) (NCT01854047) and phase 3 VENTURE (NCT02528214), dupilumab reduced annualized severe exacerbations rates (AER), improved forced expiratory volume in one second (FEV1), and was generally well tolerated in patients with uncontrolled, moderate-to-severe or oral-corticosteroid (OCS)-dependent severe asthma.
Objective: Post-hoc assessment of dupilumab efficacy vs placebo in P2B and VENTURE in patients stratified by allergic status.
Methods: Allergic asthma was defined as total serum immunoglobulin E (IgE) ≥30 IU/mL and ≥1 perennial aeroallergen-specific IgE ≥0.35 kU/L at baseline. AER, pre-bronchodilator (BD) FEV1, FEV1/forced vital capacity (FVC) ratio, asthma control (5-item Asthma Control Questionnaire [ACQ-5]), health-related quality of life (HRQoL; Asthma Quality of Life Questionnaire [AQLQ]), type 2 biomarkers, specific IgE, and OCS reduction (VENTURE only) were assessed.
Results: In patients with allergic asthma, dupilumab (P2B: pooled 200/300mg; VENTURE: 300mg) every 2 weeks vs placebo reduced AER (P2B: -60%, P<.01; VENTURE: -72%, P<.001), and, in P2B, increased pre-BD FEV1 (P<.01) and FEV1/FVC (P<.05). In both studies, dupilumab significantly improved asthma control and HRQoL and reduced most type 2 biomarkers. Dupilumab significantly reduced OCS use in VENTURE. Similar benefits were observed in patients without evidence of allergic asthma.
Conclusions: Dupilumab significantly reduced AER and improved lung function and asthma control and HRQoL in patients with or without evidence of allergic asthma.
背景：2型细胞因子白介素（IL）-4/IL-5/IL-13在包括哮喘在内的2型疾病的发病机制中起着重要作用。度普利尤单抗是一种人单克隆抗体，它阻断IL-4/IL-13的共同受体成分，抑制信号传导。在2b期（P2B）（NCT01854047）和3期VENTURE（NCT02528214）中，度普利尤单抗降低了年化严重加重率（AER），改善了一秒钟内用力呼气量（FEV1），并且在未控制、中度至重度或口服皮质类固醇（OCS）依赖性重度哮喘患者中通常耐受良好。
目的：对按过敏状态分层的P2B和VENTURE患者的度普利尤单抗疗效与安慰剂疗效进行事后评估。
方法：过敏性哮喘定义为基线时血清总免疫球蛋白E（IgE）≥30 IU/mL和≥1个常年性空气变应原特异性IgE≥0.35 kU/L。评估AER、支气管扩张前（BD）FEV1、FEV1/用力肺活量（FVC）比值、哮喘控制（5项哮喘控制问卷[ACQ-5]）、健康相关生活质量（HRQoL；哮喘生活质量问卷[AQLQ]）、2型生物标志物、特异性IgE和OCS降低（仅限VENTURE）。
结果：在过敏性哮喘患者中，与安慰剂组相比，每2周一次的度普利尤单抗（P2B:合并200/300mg；VENTURE:300mg）可降低AER（P2B:-60%，P<0.01；VENTURE：-72%，P<0.001），并且在P2B组，增加了BD前FEV1（P<0.01）和FEV1/FVC（P<0.05）。在这两项研究中，度普利尤单抗改善了哮喘控制和HRQoL，并降低了大多数2型生物标志物。度普利尤单抗显著减少了VENTURE中OCS的使用。在没有过敏性哮喘证据的患者中也观察到了类似的益处。
结论：在有或无过敏性哮喘证据的患者中，度普利尤单抗显著降低AER，改善肺功能、哮喘控制和HRQoL。
(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)
(J Allergy Clin Immunol Pract. 2022 Dec 23; S2213-2198(22)01311-3. doi: 10.1016/j.jaip.2022.11.044.)
(J Allergy Clin Immunol Pract. 2022 Dec 23; S2213-2198(22)01311-3. doi: 10.1016/j.jaip.2022.11.044.)
Dupilumab Efficacy in Patients with Uncontrolled or Oral Corticosteroid-Dependent Allergic and Non-allergic Asthma
Guy Brusselle, Santiago Quirce, Alberto Papi, Piotr Kuna, Bradley E Chipps, Nicola A Hanania, Michael Blaiss, Jérôme Msihid, Juby A Jacob-Nara, Yamo Deniz, Paul J Rowe, Rebecca Gall, Benjamin Ortiz, Michel Djandji, Amr Radwan
Abstract
Background: Type 2 cytokines interleukin (IL)-4/IL-5/IL-13 play an important role in pathogenesis of type 2 conditions, including asthma. Dupilumab, a human monoclonal antibody, blocks the shared receptor component for IL-4/IL-13, inhibiting signaling. In phase 2b (P2B) (NCT01854047) and phase 3 VENTURE (NCT02528214), dupilumab reduced annualized severe exacerbations rates (AER), improved forced expiratory volume in one second (FEV1), and was generally well tolerated in patients with uncontrolled, moderate-to-severe or oral-corticosteroid (OCS)-dependent severe asthma.
Objective: Post-hoc assessment of dupilumab efficacy vs placebo in P2B and VENTURE in patients stratified by allergic status.
Methods: Allergic asthma was defined as total serum immunoglobulin E (IgE) ≥30 IU/mL and ≥1 perennial aeroallergen-specific IgE ≥0.35 kU/L at baseline. AER, pre-bronchodilator (BD) FEV1, FEV1/forced vital capacity (FVC) ratio, asthma control (5-item Asthma Control Questionnaire [ACQ-5]), health-related quality of life (HRQoL; Asthma Quality of Life Questionnaire [AQLQ]), type 2 biomarkers, specific IgE, and OCS reduction (VENTURE only) were assessed.
Results: In patients with allergic asthma, dupilumab (P2B: pooled 200/300mg; VENTURE: 300mg) every 2 weeks vs placebo reduced AER (P2B: -60%, P<.01; VENTURE: -72%, P<.001), and, in P2B, increased pre-BD FEV1 (P<.01) and FEV1/FVC (P<.05). In both studies, dupilumab significantly improved asthma control and HRQoL and reduced most type 2 biomarkers. Dupilumab significantly reduced OCS use in VENTURE. Similar benefits were observed in patients without evidence of allergic asthma.
Conclusions: Dupilumab significantly reduced AER and improved lung function and asthma control and HRQoL in patients with or without evidence of allergic asthma.
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描述间歇性口服皮质类固醇处方模式及其与哮喘不良结局的相关性的英国观察队列研究
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真菌相关性哮喘的临床表现和结局:台湾多机构数据库研究
