University at Buffalo, State University of New York, Buffalo, NY, USA.
University of North Carolina School of Medicine, Chapel Hill, NC, USA.
Ther Adv Respir Dis. 2020 Jan-Dec;14:1753466620905278. doi: 10.1177/1753466620905278.
Combinations of a long-acting muscarinic receptor antagonist (LAMA), long-acting β-agonist (LABA), and inhaled corticosteroid (ICS) are used for patients with persistent chronic obstructive pulmonary disease (COPD) exacerbations on bronchodilator monotherapy. In this prespecified subgroup analysis, we assessed the efficacy and safety of the LAMA revefenacin in patients with COPD taking concomitant LABA, including ICS/LABA (LABA subgroup).
Efficacy data were obtained from two 12-week, replicate, placebo-controlled trials and safety data were pooled from the 12-week and a 52-week tiotropium-controlled trial. Patients received revefenacin 175 µg or placebo in the 12-week or tiotropium 18 µg in the 52-week studies. The efficacy endpoint was least squares (LS) mean change from baseline in trough forced expiratory volume in 1 second (FEV). Clinical health outcomes were assessed using the St. George's Respiratory Questionnaire (SGRQ).
Revefenacin produced similar improvements from baseline in trough FEV in the non-LABA and LABA subgroups [placebo-adjusted LS mean change (95% confidence interval) in day 85 trough FEV, 150.9 (110.3-191.6) ml and 139.2 (82.9-195.5) ml; < 0.0001 placebo]. Similar improvements were observed in SGRQ scores in the non-LABA and LABA subgroups [-3.3 (-5.4 to -1.2) and -3.4 (-6.3 to -0.6)]. Improvements in lung function and health outcomes were observed regardless of airflow obstruction severity. Revefenacin was well tolerated with more adverse events reported in the LABA than the non-LABA subgroup.
Once daily revefenacin for nebulization can be an effective and well-tolerated treatment for patients who require concomitant use of LABA with or without ICS.
CLINICALTRIALS.GOV IDENTIFIERS: NCT02512510, NCT02459080, NCT02518139
长效毒蕈碱受体拮抗剂（LAMA）、长效β-激动剂（LABA）和吸入皮质类固醇（ICS）联合使用用于支气管扩张剂单药治疗持续慢性阻塞性肺疾病（COPD）加重的患者。在本预先指定的亚组分析中，我们评估了 COPD 患者使用 LAMA 瑞福纳林的疗效和安全性，这些患者同时使用 LABA，包括 ICS/LABA（LABA 亚组）。
疗效数据来自两项为期 12 周、重复、安慰剂对照试验，安全性数据来自为期 12 周和 52 周噻托溴铵对照试验的数据进行汇总。患者在 12 周研究中接受瑞福纳林 175μg或安慰剂，在 52 周研究中接受噻托溴铵 18μg。疗效终点为从基线到谷值用力呼气量 1 秒（FEV）的最小二乘（LS）均值变化。临床健康结局使用圣乔治呼吸问卷（SGRQ）进行评估。
瑞福纳林在非 LABA 和 LABA 亚组中从基线到谷值 FEV 的改善相似[安慰剂调整的 LS 均值变化（95%置信区间）在第 85 天谷值 FEV，150.9（110.3-191.6）ml 和 139.2（82.9-195.5）ml；<0.0001 安慰剂]。非 LABA 和 LABA 亚组中 SGRQ 评分也有相似的改善[-3.3（-5.4 至-1.2）和-3.4（-6.3 至-0.6）]。无论气流阻塞严重程度如何，肺功能和健康结局的改善都有观察到。瑞福纳林耐受性良好，LABA 亚组报告的不良事件多于非 LABA 亚组。
每日一次雾化吸入瑞福纳林可有效且耐受良好，适用于需要同时使用 LABA 联合或不联合 ICS 的患者。
临床试验.gov 标识符：NCT02512510、NCT02459080、NCT02518139
