Indacaterol, a once-daily beta2-agonist, versus twice-daily beta₂-agonists or placebo for chronic obstructive pulmonary disease.

BACKGROUND: Indacaterol is an inhaled long-acting beta2-agonist that is administered once daily and has been investigated as a treatment for chronic obstructive pulmonary disease (COPD). Four different doses have been investigated (75 mcg, 150 mcg, 300 mcg and 600 mcg). The relative effects of different doses of once-daily indacaterol in the management of patients with COPD are uncertain.

OBJECTIVES: To compare the efficacy and safety of indacaterol versus placebo and alternative twice-daily long-acting beta2-agonists for the treatment of patients with stable COPD.

SEARCH METHODS: We identified trials from the Cochrane Airways Group Specialised Register of trials (CAGR), handsearched respiratory journals and meeting abstracts and searched the Novartis trials registry and ClinicalTrials.gov. The date of the most recent search was 8 November 2014.

SELECTION CRITERIA: We included all randomised controlled trials comparing indacaterol at any dose versus placebo or alternative long-acting beta2-agonists. Trials were required to be of at least 12 weeks' duration and had to include adults older than 18 years with a confirmed spirometric diagnosis of COPD.

DATA COLLECTION AND ANALYSIS: Two review authors (JBG, EJD) independently assessed for possible inclusion all citations identified as a result of the search. Disagreements were resolved through discussion or, if required, through resolution by a third review author (RWB). One review author (JBG) extracted data from trials identified by the search and entered these data into Review Manager 5.1 for statistical analysis. Data entry was cross-checked by a second review author (EJD, CJC).

MAIN RESULTS: A total of 13 trials with 9961 participants were included in the review. Ten trials with a total of 8562 participants involved an indacaterol versus placebo comparison. Five trials with a total of 4133 participants involved an indacaterol versus twice-daily beta2-agonist comparison. The comparator beta2-agonists were salmeterol, formoterol and eformoterol. One of these trials, with a total of 90 participants, provided no data that could be used in this review. Two trials included both indacaterol versus placebo and indacaterol versus twice-daily beta2-agonist comparisons. Trials were between 12 weeks and 52 weeks in duration. Overall the quality of the evidence was strong, and risk of significant bias was minimal in most of the included studies. Enrolled participants had stable COPD across a range of spirometric severities. Forced expiratory volume in 1 second (FEV1) was generally between 30% and 80% predicted, and a mean FEV1 of approximately 50% was predicted in most studies. Patients with concurrent respiratory disease, including asthma, were excluded. Concomitant use of inhaled corticosteroids was permitted.The primary objectives were to compare trough FEV1 at the end of dosing, exacerbation rates and quality of life. Significant adverse events, mortality and dyspnoea were included as secondary outcomes. Compared with placebo, a significant and clinically relevant improvement in trough FEV1 was noted with indacaterol (mean difference (MD) 149.11, 95% confidence interval (CI) 137.09 to 161.12). In addition, compared with placebo, a significant improvement in mean St George Respiratory Questionaire (SGRQ) score (MD -3.60, 95% CI -4.36 to -2.83) was reported, and the proportion of participants experiencing clinically relevant improvement in SGRQ score was significantly greater (odds ratio (OR) 1.63, 95% CI 1.46 to 1.84). Compared with twice-daily beta2-agonists, a small but statistically significant increase in trough FEV1 was seen with indacaterol (MD 61.71 mL, 95% CI 41.24 to 82.17). Differences between indacaterol and twice-daily beta2-agonists in mean SGRQ scores (MD -0.81, 95% CI -2.28 to 0.66) and in the proportions of participants achieving clinically relevant improvements in SGRQ scores (OR 1.07, 95% CI 0.87 to 1.32) were not statistically significant, but the confidence intervals are too wide to permit the conclusion that the treatments were equivalent. Data were insufficient for analysis of differences in exacerbation rates for both placebo and twice-daily beta2-agonist comparisons.

AUTHORS' CONCLUSIONS: For patients with stable COPD, use of indacaterol versus placebo results in statistically significant and clinically meaningful improvements in lung function and quality of life. The clinical benefit for lung function is at least as good as that seen with twice-daily long-acting beta2-agonists. The comparative effect on quality of life remains uncertain, as important differences cannot be excluded.