Comparative efficacy of indacaterol 150 µg and 300 µg versus fixed-dose combinations of formoterol + budesonide or salmeterol + fluticasone for the treatment of chronic obstructive pulmonary disease – a network meta-analysis

Abstract

Shannon Cope1, Gorana Capkun-Niggli2, Rupert Gale3, José R Jardim4, Jeroen P Jansen11Mapi Values, Boston, MA, USA; 2Health Economics and Outcomes Research, Novartis Pharma AG, Basel, Switzerland; 3Novartis Horsham Research Centre, Horsham, UK; 4Respiratory Division, Federal University of São Paulo, BrazilObjective: To compare efficacy of indacaterol to that of fixed-dose combination (FDC) formoterol and budesonide (FOR/BUD) and FDC salmeterol and fluticasone (SAL/FP) for the treatment of chronic obstructive pulmonary disease (COPD) based on the available randomized clinical trials (RCTs).Methods: Fifteen placebo-controlled RCTs were included that evaluated: indacaterol 150 µg (n = 5 studies), indacaterol 300 µg (n = 4), FOR/BUD 9/160 µg (n = 2), FOR/BUD 9/320 µg (n = 3), SAL/FP 50/500 µg (n = 5), and SAL/FP 50/250 µg (n = 1). Outcomes of interest were trough forced expiratory volume in 1 second (FEV1), total scores for St. George's Respiratory Questionnaire (SGRQ), and transition dyspnea index (TDI). 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.Results: Indacaterol 150 µg resulted in a higher change from baseline (CFB) in FEV1 at 12 weeks compared to FOR/BUD 9/160 µg (difference in CFB 0.11 L [95% credible intervals: 0.08, 0.13]) and FOR/BUD 9/320 µg (0.09 L [0.06, 0.11]) and was comparable to SAL/FP 50/250 µg (0.02 L [–0.04, 0.08]) and SAL/FP 50/500 µg (0.03 L [0.00, 0.06]). Similar results were observed for indacaterol 300 µg at 12 weeks and indacaterol 150/300 µg at 6 months. Indacaterol 150 µg demonstrated comparable improvement in SGRQ total score at 6 months versus FOR/BUD (both doses), and SAL/FP 50/500 µg (–2.16 point improvement [–4.96, 0.95]). Indacaterol 150 and 300 µg demonstrated comparable TDI scores versus SAL/FP 50/250 µg (0.21 points (–0.57, 0.99); 0.39 [–0.39, 1.17], respectively) and SAL/FP 50/500 µg at 6 months.Conclusion: Indacaterol monotherapy is expected to be at least as good as FOR/BUD (9/320 and 9/160 µg) and comparable to SAL/FP (50/250 and 50/500 µg) in terms of lung function. Indacaterol is also expected to be comparable to FOR/BUD (9/320 and 9/160 µg) and SAL/FP 50/500 µg in terms of health status and to SAL/FP (50/250 and 50/500 µg) in terms of breathlessness.Keywords: COPD, network meta-analysis, indacaterol