Medicines and Healthcare Products Regulatory Agency, 151 Buckingham Palace Road, London SW1W9SZ , United Kingdom.
Pharmacol Ther. 2011 May;130(2):114-43. doi: 10.1016/j.pharmthera.2010.12.008. Epub 2011 Jan 27.
Chronic obstructive pulmonary disease (COPD) is a slowly progressive, largely non-reversible pulmonary disease which is characterised by airflow limitation. It is one of the few diseases with an increasing mortality rate and by 2020 it is predicted to be the third leading cause of death. The mainstays of current treatment are long acting β₂ agonists (LABAs) coupled with an increasing reliance on inhaled corticosteroids (ICS). Two LABAs (salmeterol and formoterol) are currently licensed for COPD both as monotherapy and in combination with ICS (fluticasone propionate (FP) and budesonide respectively). A comprehensive review of the risk-benefit of these medicines in COPD is provided here which concludes that there is limited efficacy for LABAs in COPD either alone or in combination with ICS and no overall modification of the disease process. However, where directly compared, combination therapy usually provides an advantage over monotherapy. Importantly the apparent effectiveness of treatment may significantly depend upon the outcome measure chosen with some measures possibly underestimating the extent of benefit. ICS benefit may also be greater in those patients who respond to treatment. Set against this benefit are recent concerns that a number of issues related to the clinical trial design such as prior use of ICS and different withdrawal rates between groups may be significantly influencing results. Furthermore there is no evidence of a dose response relationship with regard to ICS dose. A key issue with combination therapy is the excess risk of pneumonia conferred by the use of an ICS in this patient population. This risk does not appear to be proportional to the ICS dose but may differ between FP and budesonide. We conclude that further studies are required to identify the optimal dose of ICS, in terms of both risk and benefit, and to confirm their benefit in steroid naïve patients. Furthermore it will be important to determine whether the risk of pneumonia is apparent with both FP and budesonide and to identify factors which may predict steroid responsiveness in COPD.
慢性阻塞性肺疾病（COPD）是一种进展缓慢、在很大程度上不可逆转的肺部疾病，其特征是气流受限。它是少数死亡率不断上升的疾病之一，预计到 2020 年将成为第三大致死原因。目前治疗的主要方法是长效β₂激动剂（LABA），并越来越依赖吸入皮质类固醇（ICS）。目前有两种 LABA（沙美特罗和福莫特罗）被批准用于 COPD，既可作为单一疗法，也可与 ICS 联合使用（分别为丙酸氟替卡松和布地奈德）。本文对这些药物在 COPD 中的风险效益进行了全面评估，结论是 LABA 单独或与 ICS 联合使用对 COPD 的疗效有限，也不能改变疾病进程。然而，直接比较时，联合治疗通常比单一疗法更有优势。重要的是，治疗的明显效果可能在很大程度上取决于所选择的结果测量指标，一些指标可能低估了获益的程度。ICS 获益也可能在那些对治疗有反应的患者中更大。但与此同时，最近人们担心与临床试验设计相关的一些问题，如先前使用 ICS 和组间不同的停药率，可能会对结果产生重大影响。此外，ICS 剂量与疗效之间没有剂量反应关系。联合治疗的一个关键问题是，在这一患者群体中使用 ICS 会导致肺炎的风险增加。这种风险似乎与 ICS 剂量不成比例，但可能在丙酸氟替卡松和布地奈德之间有所不同。我们的结论是，需要进一步研究以确定 ICS 的最佳剂量，既要考虑风险，也要考虑获益，并确认其在类固醇初治患者中的获益。此外，确定肺炎风险是否在丙酸氟替卡松和布地奈德中均明显以及确定预测 COPD 中类固醇反应性的因素将非常重要。
