Iqbal Ahmar, Barnes Neil C, Brooks Jean
Respiratory Franchise Medical, GSK, 5 Moore Drive, 5.3317, Research Triangle Park, NC, USA.
Respiratory Medical Franchise, GSK, Stockley Park West, 1-3 Ironbridge Road, Uxbridge, Middlesex, UB11 1BT, UK.
Clin Drug Investig. 2015 Oct;35(10):685-8. doi: 10.1007/s40261-015-0322-6.
Chronic obstructive pulmonary disease (COPD) patients with blood eosinophil (EOS) count ≥ 2% benefit from exacerbation reductions with inhaled corticosteroids (ICSs). We conducted post hoc analyses to determine if EOS count ≥ 2% is a marker for greater responsiveness to the bronchodilators umeclidinium (UMEC; long-acting muscarinic antagonist), vilanterol (VI; long-acting β2-agonist) or UMEC/VI combination.
Effects of once-daily UMEC/VI 62.5/25, UMEC 62.5 and VI 25 µg versus placebo on trough forced expiratory volume in one second (FEV1), Transition Dyspnoea Index (TDI), St George's Respiratory Questionnaire (SGRQ) scores and adverse event (AE) incidences in four completed, 6-month studies were assessed by EOS subgroup. Trough FEV1 was also evaluated by ICS use and EOS subgroup. Analyses were performed using a repeated measures model.
At baseline, 2437 of 4647 (52%) patients had EOS count ≥ 2%. Overall, ≈ 50% of patients used ICSs. At day 169, no notable variations were observed in trough FEV1 least squares mean differences between EOS subgroups versus placebo for UMEC/VI, UMEC and VI; results according to ICS use were similar. No differences were reported between EOS subgroups in TDI and SGRQ scores on day 168, or for incidences of AEs, serious AEs and AEs leading to withdrawal.
Response to UMEC/VI, UMEC and VI in terms of trough FEV1, dyspnoea and health-related quality of life was similar for COPD patients with baseline EOS counts ≥ 2 or <2%. EOS count did not appear to predict bronchodilator response in either ICS users or non-users.
血液嗜酸性粒细胞(EOS)计数≥2%的慢性阻塞性肺疾病(COPD)患者可从吸入性糖皮质激素(ICS)减少病情加重中获益。我们进行了事后分析,以确定EOS计数≥2%是否是对支气管扩张剂乌美溴铵(UMEC;长效毒蕈碱拮抗剂)、维兰特罗(VI;长效β2激动剂)或UMEC/VI联合用药反应更强的标志物。
在四项完成的6个月研究中,按EOS亚组评估每日一次使用UMEC/VI 62.5/25、UMEC 62.5和VI 25μg与安慰剂相比,对谷值一秒用力呼气量(FEV1)、过渡性呼吸困难指数(TDI)、圣乔治呼吸问卷(SGRQ)评分和不良事件(AE)发生率的影响。还通过ICS使用情况和EOS亚组评估谷值FEV1。使用重复测量模型进行分析。
基线时,4647例患者中有2437例(52%)EOS计数≥2%。总体而言,约50%的患者使用ICS。在第169天,UMEC/VI、UMEC和VI的EOS亚组与安慰剂相比,谷值FEV1最小二乘均值差异未见明显变化;根据ICS使用情况得出的结果相似。在第168天,TDI和SGRQ评分方面,EOS亚组之间以及AE、严重AE和导致停药的AE发生率方面均无差异。
基线EOS计数≥2%或<2%的COPD患者在谷值FEV1、呼吸困难和健康相关生活质量方面对UMEC/VI、UMEC和VI的反应相似。EOS计数似乎无法预测ICS使用者或非使用者的支气管扩张剂反应。