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Abstract：
BACKGROUND: Many patients with severe asthma continue to experience symptoms and exacerbations despite treatment with standard-of-care therapy. In the phase 3 NAVIGATOR study, tezepelumab significantly reduced exacerbations over 52 weeks compared with placebo in patients with severe, uncontrolled asthma. This analysis assessed the efficacy of tezepelumab in reducing asthma exacerbations in various clinically relevant subgroups of patients in NAVIGATOR.
METHODS: NAVIGATOR was a phase 3, multicentre, randomized, double-blind, placebo-controlled study. Participants (12-80 years old) with severe, uncontrolled asthma were randomized 1:1 to receive tezepelumab 210 mg or placebo subcutaneously every 4 weeks for 52 weeks. Pre-specified and post hoc analyses were performed to evaluate the annualized asthma exacerbation rate (AAER) over 52 weeks in clinically relevant subgroups of patients defined by baseline patient characteristics, medical history, exacerbation triggers, medication eligibility and medication use before and during the study.
RESULTS: Tezepelumab reduced the AAER over 52 weeks compared with placebo across a wide range of patient subgroups assessed. Reductions in exacerbations were similar across subgroups defined by baseline patient characteristics, ranging from 48% (95% confidence interval [CI]: 21, 65) to 60% (95% CI: 44, 71) in subgroups analysed by sex, smoking history and body mass index. Among the asthma-related comorbidity subgroups investigated, patients with aspirin or NSAID sensitivity had the greatest reductions in AAER with tezepelumab compared with placebo (83%; 95% CI: 66, 91). In patients eligible to receive dupilumab, tezepelumab reduced exacerbations compared with placebo by 64% (95% CI: 54, 71). Reductions in the AAER with tezepelumab compared with placebo were also observed irrespective of exacerbation trigger category and the number of asthma controller medications patients were receiving at baseline.
CONCLUSIONS: These findings further support the benefits of tezepelumab in patients with severe, uncontrolled asthma and can help to inform healthcare providers\' treatment decisions.
BACKGROUND: NAVIGATOR (NCT03347279).
METHODS: NAVIGATOR was a phase 3, multicentre, randomized, double-blind, placebo-controlled study. Participants (12-80 years old) with severe, uncontrolled asthma were randomized 1:1 to receive tezepelumab 210 mg or placebo subcutaneously every 4 weeks for 52 weeks. Pre-specified and post hoc analyses were performed to evaluate the annualized asthma exacerbation rate (AAER) over 52 weeks in clinically relevant subgroups of patients defined by baseline patient characteristics, medical history, exacerbation triggers, medication eligibility and medication use before and during the study.
RESULTS: Tezepelumab reduced the AAER over 52 weeks compared with placebo across a wide range of patient subgroups assessed. Reductions in exacerbations were similar across subgroups defined by baseline patient characteristics, ranging from 48% (95% confidence interval [CI]: 21, 65) to 60% (95% CI: 44, 71) in subgroups analysed by sex, smoking history and body mass index. Among the asthma-related comorbidity subgroups investigated, patients with aspirin or NSAID sensitivity had the greatest reductions in AAER with tezepelumab compared with placebo (83%; 95% CI: 66, 91). In patients eligible to receive dupilumab, tezepelumab reduced exacerbations compared with placebo by 64% (95% CI: 54, 71). Reductions in the AAER with tezepelumab compared with placebo were also observed irrespective of exacerbation trigger category and the number of asthma controller medications patients were receiving at baseline.
CONCLUSIONS: These findings further support the benefits of tezepelumab in patients with severe, uncontrolled asthma and can help to inform healthcare providers\' treatment decisions.
BACKGROUND: NAVIGATOR (NCT03347279).
摘要：
背景：尽管接受标准治疗，但许多重度哮喘患者仍出现症状和恶化。在第三阶段的NAVIGATOR研究中，在重度患者中，与安慰剂相比，tezepelumab在52周内显著减少了加重，不受控制的哮喘。该分析评估了在NAVIGATOR患者的各种临床相关亚组中，tezepelumab在减少哮喘加重方面的功效。
方法：NAVIGATOR是阶段3，多中心，随机化，双盲,安慰剂对照研究。参与者（12-80岁）患有严重，不受控制的哮喘以1：1的比例随机分配，每4周皮下接受tezepelumab210mg或安慰剂，共52周。在基线患者特征定义的临床相关患者亚组中，进行了预先指定和事后分析，以评估52周内的年度哮喘加重率（AAER）。病史,加重触发因素，研究前和研究期间的用药资格和用药情况。
结果：与安慰剂相比，Tezepelumab在52周内降低了AAER。根据基线患者特征定义的各个亚组的恶化减少情况相似，在按性别分析的亚组中，范围从48％（95％置信区间[CI]：21,65）到60％（95％CI：44,71），吸烟史和体重指数。在所调查的哮喘相关共病亚组中，与安慰剂组相比,对阿司匹林或NSAID敏感的患者使用tezepelumab组的AAER降低幅度最大(83%;95%CI:66,91).在有资格接受dupilumab的患者中，与安慰剂相比,tezepelumab减少了64%的急性加重(95%CI:54,71).与安慰剂相比，也观察到使用tezepelumab的AAER降低，而与恶化触发因素类别和患者在基线时接受的哮喘控制药物的数量无关。
结论：这些发现进一步支持了替齐单抗对重症患者的益处，不受控制的哮喘，可以帮助告知医疗保健提供者的治疗决定。
背景：NAVIGATOR（NCT03347279）。
方法：NAVIGATOR是阶段3，多中心，随机化，双盲,安慰剂对照研究。参与者（12-80岁）患有严重，不受控制的哮喘以1：1的比例随机分配，每4周皮下接受tezepelumab210mg或安慰剂，共52周。在基线患者特征定义的临床相关患者亚组中，进行了预先指定和事后分析，以评估52周内的年度哮喘加重率（AAER）。病史,加重触发因素，研究前和研究期间的用药资格和用药情况。
结果：与安慰剂相比，Tezepelumab在52周内降低了AAER。根据基线患者特征定义的各个亚组的恶化减少情况相似，在按性别分析的亚组中，范围从48％（95％置信区间[CI]：21,65）到60％（95％CI：44,71），吸烟史和体重指数。在所调查的哮喘相关共病亚组中，与安慰剂组相比,对阿司匹林或NSAID敏感的患者使用tezepelumab组的AAER降低幅度最大(83%;95%CI:66,91).在有资格接受dupilumab的患者中，与安慰剂相比,tezepelumab减少了64%的急性加重(95%CI:54,71).与安慰剂相比，也观察到使用tezepelumab的AAER降低，而与恶化触发因素类别和患者在基线时接受的哮喘控制药物的数量无关。
结论：这些发现进一步支持了替齐单抗对重症患者的益处，不受控制的哮喘，可以帮助告知医疗保健提供者的治疗决定。
背景：NAVIGATOR（NCT03347279）。
