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

Abstract

Shannon Cope,1 Matthias Kraemer,2 Jie Zhang,3 Gorana Capkun-Niggli,2 Jeroen P Jansen11MAPI Consultancy, Boston, MA, USA; 2Novartis Pharmaceuticals, Basel, Switzerland; 3Novartis Pharmaceuticals, East Hanover, NJ, USABackground: The purpose of this study was to update our network meta-analysis in order to compare the efficacy of indacaterol 75 µg 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 µg once daily (n = 2 studies), indacaterol 150 µg once daily (n = 5), indacaterol 300 µg once daily (n = 4), FOR/BUD 9/160 µg twice daily (n = 2), FOR/BUD 9/320 µg twice daily (n = 2), SAL/FP 50/500 µg twice daily (n = 4), and SAL/FP 50/250 µg 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 µg resulted in a greater improvement in FEV1 at 12 weeks compared with FOR/BUD 9/160 µg (difference in change from baseline 0.09 L [95% credible interval 0.04–0.13]) and FOR/BUD 9/320 µg (0.07 L [0.03–0.11]) and was comparable with SAL/FP 50/250 µg (0.00 L [-0.07–0.07]) and SAL/FP 50/500 µg (0.01 L [-0.04–0.05]). For transitional dyspnea index, data was available only for indacaterol 75 µg versus SAL/FP 50/500 µg (-0.49 points [-1.87–0.89]).Conclusion: Based on results of a network meta-analysis with and without covariates, indacaterol 75 µg is expected to be at least as efficacious as FOR/BUD (9/320 µg and 9/160 µg) and comparable with SAL/FP (50/250 µg and 50/500 µg) in terms of lung function. In terms of breathlessness (transitional dyspnea index) at 12 weeks, the results are inconclusive given the limited data.Keywords: chronic obstructive pulmonary disorder, COPD, network meta-analysis, indacaterol