背景:慢性阻塞性肺疾病(COPD)的恶化可能危及生命,并导致肺功能和生活质量不可逆转的下降。减少恶化负担的药物是未满足的需求,因为急性加重会使患者面临更多急性加重和生活质量下降的风险.Ensifentrine是一部小说,一流的,选择性,磷酸二酯酶3/4双重抑制剂具有非甾体抗炎活性和支气管扩张作用。
目的:安乐素能降低COPD急性加重的发生率和/或风险吗?
方法:预先设定的,我们对ENHANCE-1(NCT04535986)和ENHANCE-2(NCT04542057)的3期临床试验进行了汇总分析,以评估敏芬汀对加重率和风险(至首次加重的时间)的影响.这些试验包括有症状的40-80岁的中度至重度COPD患者,他们在24周内每天两次服用3mg的敏芬林或安慰剂。亚组分析和频繁的恶化转移风险是事后进行的。
结果:总计,合并分析中包括了975名敏芬治疗和574名安慰剂治疗的患者,其中62%的患者同时接受LAMA或LABA治疗,18%的患者同时接受吸入性糖皮质激素治疗.Ensifentrine与比率显着降低相关(比率,0.59;95%CI,0.43-0.80;P<0.001)和风险(风险比,0.59;95%CI,0.44-0.81;P<0.001)与安慰剂相比,中度/重度加重。急性加重率和风险的降低在患者亚组之间基本一致。包括年龄,性别,种族,背景维持药物使用,慢性支气管炎,嗜酸性粒细胞计数,COPD严重程度,和恶化史。与安慰剂相比,Ensifentrine与从不频繁加重(GOLDB)过渡到频繁加重(GOLDE)的数字延迟相关。
结论:在广泛的临床相关亚组中,在COPD患者中,Ensifentrine降低了加重率并增加了首次加重时间。
BACKGROUND: Exacerbations in chronic obstructive pulmonary disease (COPD) can be life-threatening and lead to irreversible declines in lung function and quality of life. Medications that reduce
exacerbation burden are an unmet need, as exacerbations put patients at risk for more exacerbations and decrease quality of life. Ensifentrine is a novel, first-in-class, selective, dual inhibitor of phosphodiesterase 3/4 with demonstrated nonsteroidal anti-inflammatory activity and bronchodilatory effects.
OBJECTIVE: Does ensifentrine reduce the rate and/or risk of COPD exacerbations?
METHODS: A prespecified, pooled analysis of the phase 3 clinical trials ENHANCE-1 (NCT04535986) and ENHANCE-2 (NCT04542057) was conducted to assess the effect of ensifentrine on
exacerbation rate and risk (time to first
exacerbation). The trials included symptomatic patients aged 40-80 years with moderate-to-severe COPD who received 3 mg twice-daily ensifentrine over 24 weeks or placebo. Subgroup analyses and frequent exacerbator transition risk were conducted post-hoc.
RESULTS: In total, 975 ensifentrine-treated and 574 placebo-treated patients were included in the pooled analysis, including 62% on concomitant LAMA or LABA therapy and 18% on concomitant inhaled corticosteroid therapy. Ensifentrine was associated with significant reductions in the rate (rate ratio, 0.59; 95% CI, 0.43-0.80; P < 0.001) and risk (hazard ratio, 0.59; 95% CI, 0.44-0.81; P < 0.001) of moderate/severe exacerbations compared with placebo. Reductions in the rate and risk of exacerbations were generally consistent across patient subgroups, including age, sex, race, background maintenance medication use, chronic bronchitis, eosinophil count, COPD severity, and
exacerbation history. Ensifentrine was associated with a numerical delay in transitioning from an infrequent exacerbator (GOLD B) to a frequent exacerbator (GOLD E) compared with placebo.
CONCLUSIONS: Ensifentrine reduced the rate of exacerbations and increased the time to first
exacerbation among patients with COPD across a broad range of clinically relevant subgroups.