Chalmers James D, Loebinger Michael R, Teper Ariel, McShane Pamela J, Fernandez Carlos, Fucile Sebastian, Haworth Charles S, Lauterio Melanie, van der Laan Roald, Shih Vivian H, Metersky Mark L
Division of Respiratory Medicine and Gastroenterology, University of Dundee, Dundee, UK.
Royal Brompton Hospital and National Heart and Lung Institute, Imperial College, London, UK.
ERJ Open Res. 2025 Jan 27;11(1). doi: 10.1183/23120541.00505-2024. eCollection 2025 Jan.
Bronchiectasis is a chronic inflammatory airway disease. Brensocatib, an oral, reversible inhibitor of dipeptidyl peptidase 1 (DPP1), reduces pulmonary inflammation by preventing the activation of neutrophil serine proteases. In the phase II WILLOW trial, brensocatib prolonged time to first exacerbation in patients with bronchiectasis. In this analysis we compare clinical outcomes in patients from WILLOW according to baseline disease characteristics.
Adults with bronchiectasis treated with brensocatib (10 or 25 mg) or placebo once daily were analysed by baseline Bronchiectasis Severity Index (BSI) score (≤4 (mild), 5-8 (moderate), or ≥9 (severe)), exacerbation history (2 or ≥3 in the previous year), blood eosinophil count (<300 cells per µL or ≥300 cells per µL), long-term macrolide use (≥6 months; no or yes) and culture at screening (negative or positive). End-points were time to first exacerbation, annualised exacerbation rate, change in lung function from baseline, and safety. All patients who received brensocatib were pooled and compared with placebo.
Treatment with brensocatib placebo was associated with a longer time to first exacerbation (hazard ratio (95% confidence interval), BSI: ≤4, 0.28 (0.08-0.96); 5-8, 0.75 (0.35-1.60); ≥9, 0.61 (0.35-1.04); prior exacerbations: 2, 0.56 (0.34-0.90); ≥3, 0.71 (0.32-1.59); blood eosinophils per µL: <300, 0.66 (0.42-1.06); ≥300, 0.49 (0.20-1.20); long-term macrolide use: no, 0.60 (0.38-0.94); yes, 0.60 (0.25-1.45); culture: negative, 0.54 (0.32-0.92); positive, 0.68 (0.37-1.27)). Safety results were similar across subgroups.
Patients treated with brensocatib had a numerically longer time to first exacerbation and reduced annualised rate of exacerbation placebo across all key baseline disease characteristics.
支气管扩张是一种慢性炎症性气道疾病。布瑞索卡特，一种口服的二肽基肽酶1（DPP1）可逆抑制剂，通过阻止中性粒细胞丝氨酸蛋白酶的激活来减轻肺部炎症。在II期柳树试验中，布瑞索卡特延长了支气管扩张患者首次病情加重的时间。在本分析中，我们根据基线疾病特征比较了柳树试验中患者的临床结局。
对每天接受一次布瑞索卡特（10或25毫克）或安慰剂治疗的支气管扩张成年患者，按基线支气管扩张严重程度指数（BSI）评分（≤4（轻度）、5 - 8（中度）或≥9（重度））、病情加重史（前一年2次或≥3次）、血液嗜酸性粒细胞计数（每微升<300个细胞或≥300个细胞）、长期使用大环内酯类药物（≥6个月；否或 是）以及筛查时的培养结果（阴性或阳性）进行分析。终点指标为首次病情加重时间、年化病情加重率、肺功能相对于基线的变化以及安全性。将所有接受布瑞索卡特治疗的患者合并后与安慰剂组进行比较。
与安慰剂相比，布瑞索卡特治疗使首次病情加重的时间更长（风险比（95%置信区间），BSI：≤4，0.28（0.08 - 0.96）；5 - 8，0.75（0.35 - 1.60）；≥9，0.61（0.35 - 1.04）；既往病情加重：2次，0.56（0.34 - 0.90）；≥3次，0.71（0.
