PDF(Pubmed)
Abstract：
Randomized controlled trials (RCTs) of biologics in patients with severe, uncontrolled asthma have shown differential results by baseline blood eosinophil count (BEC). In the absence of head-to-head trials, we describe the effects of biologics on annualized asthma exacerbation rate (AAER) by baseline BEC in placebo-controlled RCTs. Exacerbations associated with hospitalization or an emergency room visit, pre-bronchodilator forced expiratory volume in 1 s, Asthma Control Questionnaire score, and Asthma Quality of Life Questionnaire score were also summarized.
MEDLINE (via PubMed) was searched for RCTs of biologics in patients with severe, uncontrolled asthma and with AAER reduction as a primary or secondary endpoint. AAER ratios and change from baseline in other outcomes versus placebo were compared across baseline BEC subgroups. Analysis was limited to US Food and Drug Administration-approved biologics.
In patients with baseline BEC ≥ 300 cells/μL, AAER reduction was demonstrated with all biologics, and other outcomes were generally improved. In patients with BEC 0 to < 300 cells/μL, consistent AAER reduction was demonstrated only with tezepelumab; improvements in other outcomes were inconsistent across biologics. In patients with BEC 150 to < 300 cells/μL, consistent AAER reduction was demonstrated with tezepelumab and dupilumab (300 mg dose only), and in those with BEC 0 to < 150 cells/μL, AAER reduction was demonstrated only with tezepelumab.
The efficacy of all biologics in reducing AAER in patients with severe asthma increases with higher baseline BEC, with varying profiles across individual biologics likely due to differing mechanisms of action.
MEDLINE (via PubMed) was searched for RCTs of biologics in patients with severe, uncontrolled asthma and with AAER reduction as a primary or secondary endpoint. AAER ratios and change from baseline in other outcomes versus placebo were compared across baseline BEC subgroups. Analysis was limited to US Food and Drug Administration-approved biologics.
In patients with baseline BEC ≥ 300 cells/μL, AAER reduction was demonstrated with all biologics, and other outcomes were generally improved. In patients with BEC 0 to < 300 cells/μL, consistent AAER reduction was demonstrated only with tezepelumab; improvements in other outcomes were inconsistent across biologics. In patients with BEC 150 to < 300 cells/μL, consistent AAER reduction was demonstrated with tezepelumab and dupilumab (300 mg dose only), and in those with BEC 0 to < 150 cells/μL, AAER reduction was demonstrated only with tezepelumab.
The efficacy of all biologics in reducing AAER in patients with severe asthma increases with higher baseline BEC, with varying profiles across individual biologics likely due to differing mechanisms of action.
摘要：
背景：生物制剂在重症患者中的随机对照试验（RCT），不受控制的哮喘已通过基线血液嗜酸性粒细胞计数（BEC）显示出不同的结果。在没有正面交锋的情况下,我们通过基线BEC描述了安慰剂对照随机对照试验中生物制剂对年度哮喘加重率(AAER)的影响.与住院或急诊室就诊相关的恶化，支气管扩张剂前强制呼气量在1s内，哮喘控制问卷评分,同时总结哮喘生活质量问卷评分。
方法：MEDLINE（通过PubMed）在重症，不受控制的哮喘和AAER降低作为主要或次要终点。在基线BEC亚组之间比较了其他结果与安慰剂的AAER比率和相对于基线的变化。分析仅限于美国食品和药物管理局批准的生物制剂。
结果：在基线BEC≥300细胞/μL的患者中，所有生物制剂都证明了AAER的降低，其他结果普遍改善。在BEC0至<300细胞/μL的患者中，只有使用tezepelumab才证明了一致的AAER降低;其他结局的改善在生物制剂中不一致.在BEC150至<300细胞/μL的患者中，使用tezepelumab和dupilumab（仅300mg剂量）证明了一致的AAER降低，在BEC为0至<150个细胞/μL的人群中，仅使用tezepelumab证明了AAER降低。
结论：所有生物制剂降低重度哮喘患者AAER的疗效随基线BEC升高而增加，由于不同的作用机制，各个生物制品的概况各不相同。
方法：MEDLINE（通过PubMed）在重症，不受控制的哮喘和AAER降低作为主要或次要终点。在基线BEC亚组之间比较了其他结果与安慰剂的AAER比率和相对于基线的变化。分析仅限于美国食品和药物管理局批准的生物制剂。
结果：在基线BEC≥300细胞/μL的患者中，所有生物制剂都证明了AAER的降低，其他结果普遍改善。在BEC0至<300细胞/μL的患者中，只有使用tezepelumab才证明了一致的AAER降低;其他结局的改善在生物制剂中不一致.在BEC150至<300细胞/μL的患者中，使用tezepelumab和dupilumab（仅300mg剂量）证明了一致的AAER降低，在BEC为0至<150个细胞/μL的人群中，仅使用tezepelumab证明了AAER降低。
结论：所有生物制剂降低重度哮喘患者AAER的疗效随基线BEC升高而增加，由于不同的作用机制，各个生物制品的概况各不相同。
