Efficacy of once-daily indacaterol 75 μg relative to alternative bronchodilators in COPD: a study level and a patient level network meta-analysis

Abstract

Background: The objective of this study was to evaluate the comparative efficacy of indacaterol 75 μg once daily (OD), tiotropium 18 μg OD, salmeterol 50 μg twice daily (BID), formoterol 12 μg BID, and placebo for the treatment of chronic obstructive pulmonary disease (COPD) based on individual patient data (IPD) from randomized controlled trials (RCTs) from the indacaterol trial program and aggregate data (AD) identified from a systematic review of RCTs.

Methods: 22 RCTs were included in the AD analysis that evaluated: indacaterol 75 μg (n = 2 studies), indacaterol 150 μg n = 5 (i.e. salmeterol 50 μg) (n = 5), indacaterol 300 μg (n = 2), tiotropium 18 μg (n = 10), salmeterol 50 μg (n = 7), and formoterol 12 μg (n = 4). All of the studies except for one head-to-head comparison (tiotropium vs. salmeterol) were placebo controlled. Outcomes of interest were trough forced expiratory volume in 1 second (FEV1) and St. George's Respiratory Questionnaire (SGRQ) total score at week 12. The AD from all trials was analysed simultaneously using a Bayesian network meta-analysis (NMA) and relative treatment effects between all regimens were obtained. In a separate analysis, the IPD available from the 6 indacaterol RCTs was analysed in a NMA. Treatment-by-covariate interactions were included in both analyses to improve similarity of the trials.

Results: All interventions compared were more efficacious than placebo regarding FEV1 at 12 weeks. Indacaterol 75 μg is expected to result in a comparable FEV1 at 12 weeks to tiotropium and salmeterol based on both IPD and AD analyses. In comparison to formoterol, the IPD and AD results indicate indacaterol 75 μg is more efficacious (IPD = 0.07 L difference; 95%Credible Interval (CrI) 0.02 to 0.11; AD = 0.05 L difference; 95%CrI 0.01; 0.09). In terms of SGRQ total score at 12 weeks, indacaterol 75 μg and formoterol were more efficacious than placebo, whereas for tiotropium and salmeterol the credible intervals included zero for the AD results only (tiotropium: -2.99 points improvement versus placebo; 95%CrI -6.48 to 0.43; salmeterol:-2.52; 95%CrI: -5.34; 0.44). Both IPD and AD results suggest that indacaterol 75 μg is expected to be comparable to all active treatments.

Conclusions: Based on a synthesis of currently available AD RCT evidence as well as an IPD network meta-analysis of six RCTs, indacaterol 75 μg is expected to be at least as efficacious as formoterol and comparable to tiotropium and salmeterol regarding FEV1. Furthermore, indacaterol 75 μg shows comparable level of improvement in health-related quality of life to tiotropium, salmeterol, and formoterol, as measured by the SGRQ.

Figure 1

Flow Diagram of study selection.

Figure 2

Network of evidence.¹Note: Two 3-arm trials and one 4-arm trial were included and counted separately; therefore totals do not sum to 22.

Figure 3

FEV₁results at 12 weeks for the individual patient and aggregate meta-analyses with and without covariates for indacaterol 75 μg versus alternative treatments. AD = Aggregate data; FOR = Formoterol 12 μg; FEV₁ = Forced expiratory volume in 1 second; IND 75 = Indacaterol 75 μg; IPD = Individual patient data; SAL = Salmeterol 50 μg; TIO = Tiotropium 18 μg.

Figure 4

SGRQ total score results at 12 weeks for the individual patient and aggregate met-analyses with and without covariates for indacaterol 75 μg versus alternative treatments. AD = Aggregate data; FOR = Formoterol 12 μg; IND 75 = Indacaterol 75 μg; IPD = Individual patient data; SAL = Salmeterol 50 μg; SGRQ = St. George Respiratory Questionnaire; TIO = Tiotropium 18 μg.