Rennard Stephen I, Tashkin Donald P, McElhattan Jennifer, Goldman Mitchell, Ramachandran Sulabha, Martin Ubaldo J, Silkoff Philip E
Pulmonary Critical Care, Allergy and Sleep Medicine, University of Nebraska Medical Center, Omaha, Nebraska 68198-5885, USA.
Drugs. 2009;69(5):549-65. doi: 10.2165/00003495-200969050-00004.
Combination therapy with a long-acting bronchodilator and an inhaled corticosteroid (ICS) is recommended in patients with chronic obstructive pulmonary disease (COPD) who have frequent exacerbations. The efficacy and tolerability of the combination of budesonide/formoterol have been demonstrated in patients with COPD when administered via the dry powder inhaler (DPI) in a 1-year study and when administered via the hydrofluoroalkane (HFA) pressurized metered-dose inhaler (pMDI) in a 6-month study.
This study assessed the long-term efficacy and tolerability of budesonide/formoterol HFA pMDI in patients with moderate to very severe COPD.
This was a 12-month, randomized, double-blind, double-dummy, parallel-group, active- and placebo-controlled, multicentre study (NCT00206167) of 1, 964 patients aged >or =40 years with moderate to very severe COPD conducted from 2005 to 2007 at 237 sites in the US, Europe and Mexico. After 2 weeks of treatment based on previous therapy (ICSs, short-acting bronchodilators allowed), patients received one of the following treatments twice daily: budesonide/formoterol pMDI 160/4.5 microg x two inhalations (320/9 microg); budesonide/formoterol pMDI 80/4.5 microg x two inhalations (160/9 microg); formoterol DPI 4.5 microg x two inhalations (9 microg); or placebo.
The co-primary efficacy variables were pre-dose forced expiratory volume in 1 second (FEV1) and 1-hour post-dose FEV1. .
Budesonide/formoterol 320/9 microg demonstrated greater improvements in pre-dose FEV1 versus formoterol (p = 0.008), and both budesonide/formoterol doses demonstrated greater improvements in 1-hour post-dose FEV1 versus placebo (p < 0.001). The rate of COPD exacerbations was lower in both budesonide/formoterol groups compared with formoterol and placebo (p <or= 0.004). Both budesonide/formoterol doses were more effective than placebo (p <or= 0.006) for controlling dyspnoea and improving health status (St George's Respiratory Questionnaire). All treatments were generally well tolerated. The incidence of pneumonia was not different for active (3.4-4.0%) and placebo (5.0%) groups.
Budesonide/formoterol pMDI (320/9 microg and 160/9 microg) improved pulmonary function and reduced symptoms and exacerbations over 1 year in patients with moderate to very severe COPD. Only budesonide/formoterol pMDI 320/9 microg demonstrated greater efficacy for both co-primary variables compared with formoterol DPI 9 microg. Both budesonide/formoterol pMDI dosages were well tolerated relative to formoterol and placebo.
对于慢性阻塞性肺疾病（COPD）频繁急性加重的患者，推荐使用长效支气管扩张剂与吸入性糖皮质激素（ICS）联合治疗。在一项为期1年的研究中，布地奈德/福莫特罗通过干粉吸入器（DPI）给药，以及在一项为期6个月的研究中，通过氢氟烷烃（HFA）压力定量吸入器（pMDI）给药，已在COPD患者中证实了其联合用药的疗效和耐受性。
本研究评估布地奈德/福莫特罗HFA pMDI在中度至极重度COPD患者中的长期疗效和耐受性。
这是一项为期12个月的随机、双盲、双模拟、平行组、活性药物和安慰剂对照的多中心研究（NCT00206167），于2005年至2007年在美国、欧洲和墨西哥的237个地点对1964例年龄≥40岁的中度至极重度COPD患者进行。在根据既往治疗（允许使用ICS、短效支气管扩张剂）进行2周治疗后，患者每日两次接受以下治疗之一：布地奈德/福莫特罗pMDI 160/4.5微克×两次吸入（320/9微克）；布地奈德/福莫特罗pMDI 80/4.5微克×两次吸入（160/9微克）；福莫特罗DPI 4.5微克×两次吸入（9微克）；或安慰剂。
共同主要疗效变量为给药前1秒用力呼气容积（FEV1）和给药后1小时FEV1。
与福莫特罗相比，布地奈德/福莫特罗3(20/9微克)在给药前FEV1方面有更大改善（p = 0.008），与安慰剂相比，两种布地奈德/福莫特罗剂量在给药后1小时FEV1方面均有更大改善（p < 0.001）。与福莫特罗和安慰剂相比，两个布地奈德/福莫特罗组的COPD急性加重率均较低（p≤0.004）。两种布地奈德/福莫特罗剂量在控制呼吸困难和改善健康状况（圣乔治呼吸问卷）方面均比安慰剂更有效（p≤0.006）。所有治疗总体耐受性良好。活性药物组（3.4 - 4.0%）和安慰剂组（5.0%）的肺炎发生率无差异。
布地奈德/福莫特罗pMDI（320/9微克和160/9微克）在中度至极重度COPD患者中，1年内改善了肺功能，减轻了症状并减少了急性加重。与9微克福莫特罗DPI相比，仅布地奈德/福莫特罗pMDI 320/9微克在两个共同主要变量上均显示出更大疗效。相对于福莫特罗和安慰剂，两种布地奈德/福莫特罗pMDI剂量耐受性良好。
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