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

Background: The objective of this study was to evaluate the comparative efficacy of indacaterol 75 mu g once daily (OD), tiotropium 18 mu g OD, salmeterol 50 mu g twice daily (BID), formoterol 12 mu g 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 mu g (n = 2 studies), indacaterol 150 mu g n = 3, indacaterol 300 mu g (n = 2), tiotropium 18 mu g (n = 10), salmeterol 50 mu g (n = 6), and formoterol 12 mu g (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 mu g 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 mu g 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 mu g 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 mu g 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 mu g is expected to be at least as efficacious as formoterol and comparable to tiotropium and salmeterol regarding FEV1. Furthermore, indacaterol 75 mu g shows comparable level of improvement in health-related quality of life to tiotropium, salmeterol, and formoterol, as measured by the SGRQ.