Pulmonary Medicine, UNC School of Medicine, Chapel Hill, NC, USA.
Geisel School of Medicine at Dartmouth, Hanover, NH, USA.
Int J Chron Obstruct Pulmon Dis. 2019 Dec 19;14:2947-2958. doi: 10.2147/COPD.S157654. eCollection 2019.
Bronchodilation with muscarinic antagonists, β-agonists, and inhaled corticosteroids remains the foundation of pharmaceutical treatment for patients with stable COPD. These drugs are delivered from a variety of devices, including dry powder inhalers, pressurized metered-dose inhalers, soft-mist inhalers, or nebulizers. Nebulized delivery is often preferable in patients who are elderly, are cognitively impaired, are unable to generate sufficient inspiratory force to use their inhaler, have difficulty coordinating hand-breath activity, are too dyspneic to hold their breath for a sufficient time, and/or may be acutely ill. Revefenacin, a once-daily long-acting muscarinic antagonist for nebulization recently approved by the US FDA for the treatment of patients with COPD, was discovered and developed using "duration and lung selectivity-by-design." This strategy selected a molecule with a high lung-selective index to maximize bronchodilation and limit systemic anti-muscarinic side effects. In early-phase clinical studies, revefenacin for nebulization led to a rapid onset of bronchodilation that was sustained for 24 hrs in patients with moderate to severe COPD. Revefenacin also demonstrated minimal systemic exposure and good tolerability in these studies. Statistically and clinically significant improvements in lung function (ie, peak and/or trough FEV) relative to placebo were observed with revefenacin in Phase III clinical trials of up to 3 months in patients with moderate to very severe COPD. Revefenacin was well tolerated in Phase III clinical trials with a low incidence of systemic antimuscarinic adverse events, which is consistent with its lung-selective design. There was no evidence of an increased risk of major cardiovascular events. Patient-reported outcome data from clinical trials indicated statistically significant improvements in several disease-specific measures. Revefenacin 175 μg for nebulization provides an effective once-daily treatment option for patients with moderate to very severe COPD who require or prefer nebulized therapy.
抗胆碱能药物、β 激动剂和吸入性皮质类固醇的支气管扩张作用仍然是稳定期 COPD 患者药物治疗的基础。这些药物可以通过多种装置输送，包括干粉吸入器、压力定量吸入器、软雾吸入器或雾化器。在老年、认知障碍、无法产生足够的吸气力来使用吸入器、难以协调手-呼吸活动、呼吸困难无法屏住呼吸足够时间、或可能患有急性疾病的患者中，雾化给药通常更为可取。瑞福纳嗪（revefenacin）是一种每日一次的长效抗胆碱能药物，最近获得美国 FDA 批准用于治疗 COPD 患者，它是使用“持续时间和肺部选择性设计”发现和开发的。该策略选择了一种具有高肺选择性指数的分子，以最大限度地扩张支气管并限制全身抗毒蕈碱副作用。在早期的临床研究中，雾化瑞福纳嗪在中重度 COPD 患者中迅速起效，24 小时持续扩张支气管。在这些研究中，瑞福纳嗪还表现出最小的全身暴露和良好的耐受性。在长达 3 个月的 III 期临床试验中，与安慰剂相比，瑞福纳嗪在肺功能（即峰值和/或谷值 FEV）方面表现出统计学和临床意义上的显著改善。在 III 期临床试验中，瑞福纳嗪耐受性良好，全身抗毒蕈碱不良反应发生率低，这与其肺部选择性设计一致。没有证据表明主要心血管事件风险增加。临床试验的患者报告结果数据表明，几种疾病特异性指标均有统计学意义的改善。雾化瑞福纳嗪 175μg 为中重度 COPD 患者提供了一种有效的每日一次治疗选择，这些患者需要或更喜欢雾化治疗。
