Pulmonary Medicine, UNC School of Medicine, 321 S Columbia St, Chapel Hill, NC, 27516, USA.
Clinical Research Institute of Southern Oregon, LLC, 3860 Crater Lake Ave, Medford, OR, 97504, USA.
BMC Pulm Med. 2020 May 11;20(1):134. doi: 10.1186/s12890-020-1156-4.
Revefenacin, a once-daily, long-acting muscarinic antagonist delivered via standard jet nebulizer, increased trough forced expiratory volume in 1 s (FEV) in patients with moderate to very severe chronic obstructive pulmonary disease (COPD) in prior phase 3 trials. We evaluated the efficacy of revefenacin in patients with markers of more severe COPD.
A post hoc subgroup analysis of two replicate, randomized, phase 3 trials was conducted over 12 weeks. Endpoints included least squares change from baseline in trough FEV, St. George's Respiratory Questionnaire (SGRQ) responders, and transition dyspnea index (TDI) responders at Day 85. This analysis included patient subgroups at high risk for COPD exacerbations and compared patients who received revefenacin 175 μg and placebo: severe and very severe airflow limitation (percent predicted FEV 30%-< 50% and < 30%), 2011 Global Initiative for Chronic Obstructive Lung Disease (GOLD) D, reversibility (≥ 12% and ≥ 200 mL increase in FEV) to short-acting bronchodilators, concurrent use of long-acting β agonists and/or inhaled corticosteroids, older age (> 65 and > 75 years), and comorbidity risk factors.
Revefenacin demonstrated significant improvements in FEV versus placebo at Day 85 among the intention-to-treat (ITT) population and all subgroups. Additionally, there was a greater number of SGRQ and TDI responders in the ITT population and the majority of subgroups analyzed among patients who received revefenacin versus placebo. For the SGRQ responders, the odds of response (odds ratio > 2.0) were significantly greater in the revefenacin arm versus the placebo arm among the severe airflow obstruction, very severe airflow obstruction and 2011 GOLD D subgroups. For the TDI responders, the odds of response (odds ratio > 2.0) were significantly greater among the severe airflow obstruction subgroup and patients aged > 75 years.
Revefenacin showed significantly greater improvements in FEV versus placebo in the ITT population and all subgroups. Furthermore, there were a greater number of SGRQ and TDI responders in the ITT population, and in the majority of patient subgroups among patients who received revefenacin versus placebo. Based on the data presented, revefenacin could be a therapeutic option among patients with markers of more severe COPD.
Clinical trials registered with www.clinicaltrials.gov (Studies 0126 [NCT02459080; prospectively registered 22 May 2015] and 0127 [NCT02512510; prospectively registered 28 July 2015]).
瑞福纳嗪是一种每日一次、长效的毒蕈碱拮抗剂，通过标准射流雾化器给药，在中度至重度慢性阻塞性肺疾病（COPD）患者中增加了谷值用力呼气量 1 秒（FEV1）。在之前的三项 3 期试验中，瑞福纳嗪已显示出对患者有疗效。
对两项重复、随机、3 期试验的事后亚组分析进行了 12 周的评估。终点包括从基线到第 85 天的谷值 FEV1、圣乔治呼吸问卷（SGRQ）应答者和过渡性呼吸困难指数（TDI）应答者的最小二乘变化。该分析包括 COPD 加重风险较高的患者亚组，并比较了接受瑞福纳嗪 175μg 和安慰剂的患者：严重和非常严重气流受限（预测 FEV 的 30%-<50%和<30%）、2011 年全球慢性阻塞性肺疾病倡议（GOLD）D 级、对短效支气管扩张剂的可逆性（≥12%和≥200mL FEV 增加）、同时使用长效β激动剂和/或吸入皮质激素、年龄较大（>65 岁和>75 岁）和合并症风险因素。
在意向治疗（ITT）人群和所有亚组中，瑞福纳嗪在第 85 天与安慰剂相比，FEV 有显著改善。此外，与安慰剂相比，在接受瑞福纳嗪的 ITT 人群和分析的大多数亚组中，SGRQ 和 TDI 应答者更多。对于 SGRQ 应答者，在严重气流受限、非常严重气流受限和 2011 年 GOLD D 亚组中，与安慰剂相比，瑞福纳嗪组的应答几率（比值比>2.0）显著更高。对于 TDI 应答者，在严重气流受限亚组和年龄>75 岁的患者中，与安慰剂相比，应答几率（比值比>2.0）显著更高。
与安慰剂相比，瑞福纳嗪在 ITT 人群和所有亚组中均显示出显著改善 FEV。此外，与安慰剂相比，在接受瑞福纳嗪的 ITT 人群中，以及在接受瑞福纳嗪的大多数患者亚组中，SGRQ 和 TDI 的应答者更多。基于所提供的数据，瑞福纳嗪可能是 COPD 加重风险较高患者的一种治疗选择。
在美国临床试验数据库（ClinicalTrials.gov）注册的临床试验（0126 研究[NCT02459080；前瞻性注册 2015 年 5 月 22 日]和 0127 研究[NCT02512510；前瞻性注册 2015 年 7 月 28 日]）。
