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

Objective: 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 (FEV(1)), 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 FEV(1) 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; indacaterol; network meta-analysis.

Figure 1

Flow diagram of study selection. Abbreviations: CSR, complete study reports; FDC, fixed-dose combinations; PICOS, patients, interventions, comparators, outcomes, and study design.

Figure 2

Network of studies. Note: ^aStudies included predominantly Asian patients. Abbreviations: BID, twice daily; FDC, fixed-dose combinations; FOR/BUD, FDC formoterol and budesonide; ICS, inhaled corticosteroids; OD, once daily; SAL/FP, FDC salmeterol and fluticasone proprionate.

Figure 3

Impact of adjustment for differences in effect-modifiers across studies: difference in indacaterol 150 μg versus alternatives for CFB in FEV₁ at 12 weeks and 95% credible Intervals. Abbreviations: CFB, change from baseline; FEV₁, forced expiratory volume in 1 second; FOR/BUD 9/160, fixed-dose formoterol and budesonide 9/160 μg; FOR/BUD 9/320, fixed-dose formoterol and budesonide 9/320 μg; IND 150, indacaterol 150 μg; PLBO, placebo; SAL/FP 50/250, fixed-dose salmeterol and fluticasone proprionate 50/250 μg; SAL/FP 50/500, fixed-dose salmeterol and fluticasone proprionate 50/500 μg.