特泽鲁单抗在广泛的严重、未控制的哮喘患者群体中的临床反应和治疗中的临床缓解：NAVIGATOR 和 DESTINATIO
2024/11/29
特泽鲁单抗在广泛的严重、未控制的哮喘患者群体中的临床反应和治疗中的临床缓解：NAVIGATOR 和 DESTINATION 研究超过2年的结果
摘要背景：在哮喘中，临床应答的特征是治疗后疾病改善，而临床缓解的特征是疾病长期稳定，有或没有持续治疗。
目的：在严重，不受控制的哮喘的NAVIGATOR（NCT03347279）和DESTINATION（NCT03706079）研究中评估了接受特泽鲁单抗治疗的患者中对治疗有应答的患者和达到治疗临床缓解的患者的比例。
方法：NAVIGATOR和DESTINATION是第3阶段，随机，双盲，安慰剂对照研究；DESTINATION是NAVIGATOR的扩展。临床完全缓解被定义为实现以下所有目标：比前一年减少≥50%的恶化程度，支气管扩张剂前 （BD） 1 秒用力呼气容积 （FEV（1）） 改善 ≥100 mL 或 ≥5%，哮喘控制问卷 （ACQ）-6 评分改善 ≥0.5 和医生对哮喘改善的评估。治疗中临床缓解定义为 ACQ-6 总分 ≤1.5，肺功能稳定（BD 前 FEV（1）>基线的 95%），并且在评估的时间段内没有恶化或使用口服皮质类固醇。
结果：在第0-52周（46%比24%；OR:2.83[95%可信区间：2.10-3.82]）和第0-52周（28.5%比21.9%；OR:1.44[95%可信区间：0.95-2.19]）和>52-104周（33.5%比26.7%；OR:1.44[95%可信区间：0.97-2.14]）的治疗临床缓解率高于安慰剂组。在第52周获得治疗期临床缓解和完全临床缓解的接受特泽鲁单抗治疗的患者在基线时具有更好的肺功能保存和较低的炎症生物标志物，并且在研究前12个月内恶化较少。
结论：在严重、未控制的哮喘患者中，与安慰剂相比，特泽鲁单抗治疗与实现临床完全缓解和治疗中临床缓解的可能性增加相关。两者都是临床上重要的结局，但可能由不同的患者特征驱动。
(中日友好医院呼吸与危重症医学科 万静萱 摘译 林江涛 审校)
(Eur Respir J 2024 Sep 26;0(0). DOI: 10.1183/13993003.00316-2024.IF：12.339)
(Eur Respir J 2024 Sep 26;0(0). DOI: 10.1183/13993003.00316-2024.IF：12.339)
Clinical response and on-treatment clinical remission with tezepelumab in a broad population of patients with severe, uncontrolled asthma: results over 2 years from the NAVIGATOR and DESTINATION studies.
Michael E, Wechsler; Guy, Brusselle;
Abstrast
Background: In asthma, clinical response is characterized by disease improvement with treatment, whereas clinical remission is characterized by long-term disease stabilization with or without ongoing treatment.
Objective: The proportion of patients receiving tezepelumab who responded to treatment and those who achieved on-treatment clinical remission was assessed in the NAVIGATOR (NCT03347279) and DESTINATION (NCT03706079) studies of severe, uncontrolled asthma.
Methods: NAVIGATOR and DESTINATION were phase 3, randomized, double-blind, placebo-controlled studies; DESTINATION was an extension of NAVIGATOR.Complete clinical response was defined as achieving all of the following: ≥50% reduction in exacerbations versus the previous year, improvements in pre-bronchodilator (BD) forced expiratory volume in 1 s (FEV(1)) of ≥100 mL or ≥5%, improvements in Asthma Control Questionnaire (ACQ)-6 score of ≥0.5 and physicians' assessment of asthma improvement. On-treatment clinical remission was defined as an ACQ-6 total score ≤1.5, stable lung function (pre-BD FEV(1) >95% of baseline) and no exacerbations or use of oral corticosteroids during the time periods assessed.
Results：Higher proportions of tezepelumab than placebo recipients achieved complete clinical response over weeks 0-52 (46% versus 24%; OR: 2.83 [95% CI: 2.10-3.82]), and on-treatment clinical remission over weeks 0-52 (28.5% versus 21.9%; OR: 1.44 [95% CI: 0.95-2.19]) and weeks >52-104 (33.5% versus 26.7%; OR: 1.44 [95% CI: 0.97-2.14]). Tezepelumab recipients who achieved on-treatment clinical remission versus complete clinical response at week 52 had better preserved lung function and lower inflammatory biomarkers at baseline, and fewer exacerbations in the 12 months before the study.
Conclusions: Among patients with severe, uncontrolled asthma, tezepelumab treatment was associated with an increased likelihood of achieving complete clinical response and on-treatment clinical remission compared with placebo. Both are clinically important outcomes but may be driven by different patient characteristics.
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