■到目前为止,研究前生物标志物水平和后生物结局之间的关联的研究仅限于单一生物标志物和结构化临床试验的生物疗效评估.
■阐明在现实生活中,前生物学个体生物标志物水平或其组合与哮喘预后前至后生物学变化的关联。
■这是一个基于注册表的,使用来自23个国家的数据进行队列研究,与国际严重哮喘登记处(2017年5月至2023年2月)共享数据。研究的生物标志物(最高前生物水平)是免疫球蛋白E(IgE),血嗜酸性粒细胞计数(BEC)和部分呼出气一氧化氮(FeNO)。三个哮喘结果域中的每一个的前至大约12个月的生物学变化(即恶化率,症状控制和肺功能),研究了这种变化与生物前生物标志物的相关性,包括个体和联合生物标志物.
■总的来说,3751名患者开始使用生物制剂并纳入分析。在任何生物类别的前生物BEC和前至后生物恶化率之间均未发现关联。然而,较高的前生物BEC和FeNO均与抗IgE和抗IL5/5R的FEV1生物学后改善有关,具有抗IL4Rα的趋势。随着生物前BEC的增加,平均FEV1在抗IgE后改善了27-178mL(250至1000个细胞/μL),并通过43-216毫升和129-250毫升后抗IL5/5R和-抗IL4Rα,分别沿相同的BEC梯度。沿FeNO梯度(25-100ppb)的相应改进为41-274mL,69-207毫升和148-224毫升的抗IgE,抗IL5/5R,和抗IL4Rα,分别。较高的基线BEC也与抗IL5/5R生物制剂后哮喘失控的概率较低(OR0.392;p=0.001)相关。对于所有生物制剂评估的所有结果,前生物IgE是随后的前至后生物变化的不良预测因子。BEC+FeNO的组合略微改善了生物后FEV1增加的预测(调整后的R2:0.751),与BEC(调整后的R2:0.747)或单独的FeNO(调整后的R2:0.743)相比(分别为p=0.005和<0.001);然而,这一预测并未因添加IgE而得到改善.
■较高基线BEC的能力,FeNO及其联合预测生物学相关肺功能改善可能会鼓励对肺功能受损或有加速肺功能下降风险的患者进行早期干预。
UNASSIGNED: To date, studies investigating the association between pre-biologic biomarker levels and post-biologic outcomes have been limited to single biomarkers and assessment of biologic efficacy from structured clinical trials.
UNASSIGNED: To elucidate the associations of pre-biologic individual biomarker levels or their combinations with pre-to-post biologic changes in asthma outcomes in real-life.
UNASSIGNED: This was a registry-based, cohort study using data from 23 countries, which shared data with the International Severe Asthma Registry (May 2017-February 2023). The investigated biomarkers (highest pre-biologic levels) were immunoglobulin E (IgE), blood eosinophil count (BEC) and fractional exhaled nitric oxide (FeNO). Pre- to approximately 12-month post-biologic change for each of three asthma outcome domains (i.e. exacerbation rate, symptom control and lung function), and the association of this change with pre-biologic biomarkers was investigated for individual and combined biomarkers.
UNASSIGNED: Overall, 3751 patients initiated biologics and were included in the analysis. No association was found between pre-biologic BEC and pre-to-post biologic change in exacerbation rate for any biologic class. However, higher pre-biologic BEC and FeNO were both associated with greater post-biologic improvement in
FEV1 for both anti-IgE and anti-IL5/5R, with a trend for anti-IL4Rα. Mean
FEV1 improved by 27-178 mL post-anti-IgE as pre-biologic BEC increased (250 to 1000 cells/µL), and by 43-216 mL and 129-250 mL post-anti-IL5/5R and -anti-IL4Rα, respectively along the same BEC gradient. Corresponding improvements along a FeNO gradient (25-100 ppb) were 41-274 mL, 69-207 mL and 148-224 mL for anti-IgE, anti-IL5/5R, and anti-IL4Rα, respectively. Higher baseline BEC was also associated with lower probability of uncontrolled asthma (OR 0.392; p=0.001) post-biologic for anti-IL5/5R. Pre-biologic IgE was a poor predictor of subsequent pre-to-post-biologic change for all outcomes assessed for all biologics. The combination of BEC + FeNO marginally improved the prediction of post-biologic
FEV1 increase (adjusted R2: 0.751), compared to BEC (adjusted R2: 0.747) or FeNO alone (adjusted R2: 0.743) (p=0.005 and <0.001, respectively); however, this prediction was not improved by the addition of IgE.
UNASSIGNED: The ability of higher baseline BEC, FeNO and their combination to predict biologic-associated lung function improvement may encourage earlier intervention in patients with impaired lung function or at risk of accelerated lung function decline.