度普利尤单抗减少中-重度哮喘患者急性发作，且与生物标志物的变化无关
2024/06/11
摘要
背景：呼出气一氧化氮(FeNO)和血嗜酸性粒细胞计数较基线的变化可能与度普利尤单抗治疗中-重度哮喘患者的疗效相关。
目的：这项事后分析研究了QUEST（NCT02414854）中使用安慰剂和度普利尤单抗治疗的未控制的中-重度哮喘患者的生物标志物变化。
方法：对第52周的年重度急性发作率（AER）和支气管舒张剂前第1秒用力呼气容积（FEV1）较基线的变化进行样条分析，作为第52周FeNO变化倍数和第0-12周血嗜酸性粒细胞计数最大变化倍数的函数。
结果：联合安慰剂组和度普利尤单抗组分别包含638例和1264例患者。与安慰剂组相比，度普利尤单抗组患者的FeNO水平在第2周迅速下降，然后逐渐下降至第52周；血嗜酸性粒细胞计数在度普利尤单抗组先增加，然后在两个治疗组（200mg或300mg）中均观察到较基线略下降。QUEST研究期间的AER与两个治疗组的生物标志物变化均无显著相关性。第52周支气管扩张剂前FEV1相对于基线的变化与两组FeNO的倍数变化呈负相关，度普利尤单抗组和安慰剂组曲线之间存在显著差异（p=0.014），并且与两组血嗜酸性粒细胞计数的倍数变化呈正相关（p=0.022）。
结论：无论治疗组剂量的不同（200mg或300mg），FeNO和血嗜酸性粒细胞计数的相对变化均与AER无关。然而，这两种生物标志物的变化对肺功能改善均具有预测价值；而FeNO的预测价值是度普利尤单抗组特有的。
Dupilumab reduces exacerbations independent of changes in biomarkers in moderate-to-severe asthma
Ian D Pavord, Thomas B Casale, Jonathan Corren, Mark J FitzGerald, Yamo Deniz, Arman Altincatal, Rebecca Gall, Nami Pandit-Abid, Amr Radwan, Juby A Jacob-Nara, Paul J Rowe, William W Busse
J Allergy Clin Immunol Pract. 2024 Mar 28:S2213-2198(24)00306-4. doi: 10.1016/j.jaip.2024.03.031. Online ahead of print. PMID: 38555079
Abstract
BACKGROUND: Changes from baseline in fractional exhaled nitric oxide (FeNO) and blood eosinophil count (Eos) may be related to efficacy outcomes in dupilumab-treated patients with moderate-to-severe asthma.
OBJECTIVE: This post-hoc analysis investigated biomarker changes in placebo- and dupilumab-treated patients with uncontrolled moderate-to-severe asthma enrolled in QUEST (NCT02414854).
METHODS: Spline analyses of annualized severe exacerbation rate (AER) and change from baseline in pre-bronchodilator (BD) forced expiratory volume in 1 second (FEV1) at Week 52 were performed as a function of fold-change in FeNO at Week 52, and maximum fold-change in Eos over Week 0-12 (also change from baseline in pre64 bronchodilator FEV1 at Week 12).
RESULTS: The combined placebo and dupilumab groups comprised 638 and 1264 patients, respectively. FeNO levels declined rapidly by Week 2 then gradually to Week 52 in patients treated with dupilumab vs placebo; Eos counts, after initially increasing with dupilumab, declined slightly from baseline in both treatment groups. AER during QUEST showed no significant association with change in biomarkers in either treatment group. Change from baseline in pre-bronchodilator FEV1 at Week 52 was inversely associated with fold-change in FeNO in both groups, with significant difference between the dupilumab and placebo curves (P = .014) and was positively associated with fold change in Eos in both groups (P = .022).
CONCLUSION: Relative changes in FeNO and Eos were not associated with AER, regardless of treatment arm. However, changes in both biomarkers showed predictive value for lung function improvement; for FeNO this was specific to the dupilumab treatment arm.
背景：呼出气一氧化氮(FeNO)和血嗜酸性粒细胞计数较基线的变化可能与度普利尤单抗治疗中-重度哮喘患者的疗效相关。
目的：这项事后分析研究了QUEST（NCT02414854）中使用安慰剂和度普利尤单抗治疗的未控制的中-重度哮喘患者的生物标志物变化。
方法：对第52周的年重度急性发作率（AER）和支气管舒张剂前第1秒用力呼气容积（FEV1）较基线的变化进行样条分析，作为第52周FeNO变化倍数和第0-12周血嗜酸性粒细胞计数最大变化倍数的函数。
结果：联合安慰剂组和度普利尤单抗组分别包含638例和1264例患者。与安慰剂组相比，度普利尤单抗组患者的FeNO水平在第2周迅速下降，然后逐渐下降至第52周；血嗜酸性粒细胞计数在度普利尤单抗组先增加，然后在两个治疗组（200mg或300mg）中均观察到较基线略下降。QUEST研究期间的AER与两个治疗组的生物标志物变化均无显著相关性。第52周支气管扩张剂前FEV1相对于基线的变化与两组FeNO的倍数变化呈负相关，度普利尤单抗组和安慰剂组曲线之间存在显著差异（p=0.014），并且与两组血嗜酸性粒细胞计数的倍数变化呈正相关（p=0.022）。
结论：无论治疗组剂量的不同（200mg或300mg），FeNO和血嗜酸性粒细胞计数的相对变化均与AER无关。然而，这两种生物标志物的变化对肺功能改善均具有预测价值；而FeNO的预测价值是度普利尤单抗组特有的。
(四川大学华西医院呼吸与危重症医学科 谯猗丹1 王霁1 王刚1译)
(J Allergy Clin Immunol Pract. 2024 Mar 28:S2213-2198(24)00306-4. doi: 10.1016/j.jaip.2024.03.031. Online ahead of print. PMID: 38555079)
(J Allergy Clin Immunol Pract. 2024 Mar 28:S2213-2198(24)00306-4. doi: 10.1016/j.jaip.2024.03.031. Online ahead of print. PMID: 38555079)
Dupilumab reduces exacerbations independent of changes in biomarkers in moderate-to-severe asthma
Ian D Pavord, Thomas B Casale, Jonathan Corren, Mark J FitzGerald, Yamo Deniz, Arman Altincatal, Rebecca Gall, Nami Pandit-Abid, Amr Radwan, Juby A Jacob-Nara, Paul J Rowe, William W Busse
J Allergy Clin Immunol Pract. 2024 Mar 28:S2213-2198(24)00306-4. doi: 10.1016/j.jaip.2024.03.031. Online ahead of print. PMID: 38555079
Abstract
BACKGROUND: Changes from baseline in fractional exhaled nitric oxide (FeNO) and blood eosinophil count (Eos) may be related to efficacy outcomes in dupilumab-treated patients with moderate-to-severe asthma.
OBJECTIVE: This post-hoc analysis investigated biomarker changes in placebo- and dupilumab-treated patients with uncontrolled moderate-to-severe asthma enrolled in QUEST (NCT02414854).
METHODS: Spline analyses of annualized severe exacerbation rate (AER) and change from baseline in pre-bronchodilator (BD) forced expiratory volume in 1 second (FEV1) at Week 52 were performed as a function of fold-change in FeNO at Week 52, and maximum fold-change in Eos over Week 0-12 (also change from baseline in pre64 bronchodilator FEV1 at Week 12).
RESULTS: The combined placebo and dupilumab groups comprised 638 and 1264 patients, respectively. FeNO levels declined rapidly by Week 2 then gradually to Week 52 in patients treated with dupilumab vs placebo; Eos counts, after initially increasing with dupilumab, declined slightly from baseline in both treatment groups. AER during QUEST showed no significant association with change in biomarkers in either treatment group. Change from baseline in pre-bronchodilator FEV1 at Week 52 was inversely associated with fold-change in FeNO in both groups, with significant difference between the dupilumab and placebo curves (P = .014) and was positively associated with fold change in Eos in both groups (P = .022).
CONCLUSION: Relative changes in FeNO and Eos were not associated with AER, regardless of treatment arm. However, changes in both biomarkers showed predictive value for lung function improvement; for FeNO this was specific to the dupilumab treatment arm.
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