Jones Paul W
Institute for Infection and Immunity, Faculty of Respiratory Medicine, St George's, University of London, London, UK.
Int J Chron Obstruct Pulmon Dis. 2015 Mar 26;10:677-87. doi: 10.2147/COPD.S76520. eCollection 2015.
Three long-acting muscarinic antagonists (LAMAs) are now available in Europe, providing clinicians and patients with a choice of interventions, which is important in COPD, which is clinically a heterogeneous disease. The first LAMA, tiotropium, has been widely used over the last decade as a once-daily maintenance therapy in stable COPD to improve patients' health-related quality of life and to reduce the risk of exacerbations. Administered via the HandiHaler(®) device, it is safe and well tolerated. Another new once-daily LAMA, glycopyrronium, has also been shown to improve health status and reduce exacerbations, and is well tolerated. The subject of this review is a third LAMA, aclidinium bromide, which was approved as a twice-daily maintenance bronchodilator treatment. In the pivotal Phase III clinical trials, patients receiving aclidinium achieved significantly greater improvements in lung function, reductions in breathlessness, and improvements in health status compared with placebo, for up to 24 weeks. In continuation studies, these improvements were sustained for up to 52 weeks. Pooled data showed exacerbation frequency was significantly reduced with aclidinium versus placebo. Preclinical and pharmacological studies demonstrating low systemic bioavailability and a low propensity to induce cardiac arrhythmias were translated into a favorable tolerability profile in the clinical trial program - the adverse event profile of aclidinium was similar to placebo, with a low incidence of anticholinergic and cardiac adverse events. While additional studies are needed to evaluate its full clinical potential, aclidinium is an important part of this recent expansion of LAMA therapeutic options, providing clinicians and patients with an effective and well-tolerated COPD treatment.
目前欧洲已有三种长效毒蕈碱拮抗剂(LAMA)可供使用,为临床医生和患者提供了多种干预选择,这对于慢性阻塞性肺疾病(COPD)这种临床异质性疾病而言至关重要。首款LAMA噻托溴铵在过去十年中已被广泛用作稳定期COPD的每日一次维持治疗药物,以改善患者的健康相关生活质量并降低急性加重风险。通过HandiHaler(®)装置给药,它安全且耐受性良好。另一种新型每日一次的LAMA格隆溴铵也已被证明可改善健康状况并减少急性加重,且耐受性良好。本综述的主题是第三种LAMA阿地溴铵,它被批准为每日两次的维持性支气管扩张剂治疗药物。在关键的III期临床试验中,与安慰剂相比,接受阿地溴铵治疗的患者在长达24周的时间里,肺功能有显著更大改善,呼吸困难减轻,健康状况得到改善。在后续研究中,这些改善持续了长达52周。汇总数据显示,与安慰剂相比,阿地溴铵可显著降低急性加重频率。临床前和药理学研究表明其全身生物利用度低且诱发心律失常的倾向低,这在临床试验项目中转化为良好的耐受性——阿地溴铵的不良事件谱与安慰剂相似,抗胆碱能和心脏不良事件的发生率较低。虽然还需要进一步研究来评估其全部临床潜力,但阿地溴铵是近期LAMA治疗选择扩展的重要组成部分,为临床医生和患者提供了一种有效且耐受性良好的COPD治疗方法。