ArticlesEfficacy and safety of once-daily QVA149 compared with twice-daily salmeterol–fluticasone in patients with chronic obstructive pulmonary disease (ILLUMINATE): a randomised, double-blind, parallel group study
Introduction
In 2011, the Global Initiative for Chronic Obstructive Lung Disease (GOLD) released new recommendations for the management of chronic obstructive pulmonary disease (COPD).1 According to the GOLD 2011 strategy, drug treatment should be predicated according to the level of patient's risk, defined in terms of airflow limitation, symptoms, and history of exacerbations.1 Longacting bronchodilators are the preferred option, either alone or in combination with an inhaled corticosteroid (ICS), for maintenance treatment of patients with all but the lowest risk category of COPD. The use of ICS should be reserved for those patients at high risk (group C and D),1 defined by a history of frequent exacerbations (two or more a year) or severe airflow limitation (forced expiratory volume in 1 second [FEV1] <50% predicted1), who stand to gain the most benefit from treatment. Despite these recommendations, there is evidence of widespread and possibly inappropriate use of ICS in patients with more moderate disease2, 3, 4 (equivalent to group B).1 Whether such patients would benefit from an approach of intensive bronchodilation rather than with a combination of an ICS and a longacting β2-agonist (LABA) has not previously been explored.
The strategy of combining bronchodilators of different pharmacological classes in COPD is to provide additional benefit over the use of single agents, without significantly increasing the risk of side-effects.1, 5, 6 Concurrent treatment with LABAs and longacting muscarinic antagonists (LAMAs) have shown significant improvements in lung function compared with either type of therapy used alone.5, 7, 8
Our study compares a dual bronchodilator (QVA149; a once-daily, fixed-dose combination of the LABA indacaterol and the LAMA glycopyrronium [NVA237] in development for the treatment of COPD) and a combined LABA and ICS (salmeterol–fluticasone [SFC]; twice a day), in patients with moderate-to-severe COPD and no history of exacerbations in the previous year. Our study hopes to address the question of whether, in a largely low-risk but symptomatic population of COPD patients, intensive bronchodilator maintenance treatment alone (with two longacting bronchodilators) is safe and offers benefits compared with the common practice of using a combined LABA and ICS.
Section snippets
Study design
ILLUMINATE was a multicentre (93 centres in ten countries [appendix]), randomised, double-blind, double-dummy, parallel-group, 26-week study in patients with moderate-to-severe COPD (GOLD II or III as defined in the 2009 GOLD guidelines; figure 1).9 The first patient was enrolled on March 25, 2011, and the last patient completed on March 12, 2012.
We enrolled men and women 40 years of age or older, current or former smokers with a smoking history of at least 10 pack-years, post-bronchodilator FEV
Results
523 patients were randomised and 522 (QVA149 n=258; SFC n=264) were included in the safety and full analysis sets. One patient was randomised in error and did not receive any study medication, and was excluded. 432 patients completed the study (completion and withdrawal rates were similar between the two treatment groups: 83% completion rate for QVA149 and 82·2% for SFC); the primary reasons for discontinuation were adverse events and withdrawal of consent (figure 2; see appendix for patient
Discussion
QVA149 once a day provides significantly better and clinically relevant improvements in lung function compared with SFC administered twice a day in patients with moderate-to-severe COPD. It also provided improvements in important patient-reported outcomes such as dyspnoea and rescue medication use compared with SFC. The safety of both QVA149 and SFC were acceptable, with the overall incidence of adverse events being similar between the two groups.
The ILLLUMINATE study addresses the gap in
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