Efficacy of indacaterol 75 μg versus fixed-dose combinations of formoterol-budesonide or salmeterol-fluticasone for COPD: a network meta-analysis

Background: The purpose of this study was to update our network meta-analysis in order to compare the efficacy of indacaterol 75 mu g with that of a fixed-dose combination of formoterol and budesonide (FOR/BUD) and a fixed-dose combination salmeterol and fluticasone (SAL/FP) for the treatment of chronic obstructive pulmonary disease (COPD) based on evidence identified previously in addition to two new randomized clinical trials. Methods: Fifteen randomized, placebo-controlled clinical trials including COPD patients were evaluated: indacaterol 75 mu g once daily (n = 2 studies), indacaterol 150 mu g once daily (n = 5), indacaterol 300 mu g once daily (n = 4), FOR/BUD 9/160 mu g twice daily (n = 2), FOR/BUD 9/320 mu g twice daily (n = 2), SAL/FP 50/500 mu g twice daily (n = 4), and SAL/FP 50/250 mu g twice daily (n = 1). All trials were analyzed simultaneously using a Bayesian network meta-analysis and relative treatment effects between all regimens were obtained. Treatment-by-covariate interactions were included where possible to improve the similarity of the trials. Outcomes of interest were trough forced expiratory volume in 1 second (FEV1) and transitional dyspnea index at 12 weeks. Results: Based on the results without adjustment for covariates, indacaterol 75 mu g resulted in a greater improvement in FEV1 at 12 weeks compared with FOR/BUD 9/160 mu g (difference in change from baseline 0.09 L [95% credible interval 0.04-0.13]) and FOR/BUD 9/320 mu g (0.07 L [ 0.03-0.11]) and was comparable with SAL/FP 50/250 mu g (0.00 L [-0.07-0.07]) and SAL/FP 50/500 mu g (0.01 L [-0.04-0.05]). For transitional dyspnea index, data was available only for indacaterol 75 mu g versus SAL/FP 50/500 mu g (-0.49 points [-1.87-0.89]). Conclusion: Based on results of a network meta-analysis with and without covariates, indacaterol 75 mu g is expected to be at least as efficacious as FOR/BUD (9/320 mu g and 9/160 mu g) and comparable with SAL/FP (50/250 mu g and 50/500 mu g) in terms of lung function. In terms of breathlessness (transitional dyspnea index) at 12 weeks, the results are inconclusive given the limited data.