PURPOSE: To evaluate the comparative efficacy of indacaterol 75μg once-daily (OD) compared to tiotropium, salmeterol, and formoterol by combining data from the indacaterol trial program using indirect comparison and meta-analysis techniques.
METHODS: Individual patient data (IPD) were available from six randomized controlled trials (RCTs) comparing indacaterol 75μg to placebo (B2354 and B2355), indacaterol 150μg to placebo (INLIGHT-1 and 2, and INHANCE), salmeterol 50μg (INLIGHT-2), and tiotropium 18μg open label (INHANCE), and indacaterol 300μg to formoterol 12μg (INVOLVE). Results from these RCTs were synthesised simultaneously by means of a Bayesian network meta-analysis using IPD. As a result, relative efficacy estimates between all regimens were obtained. The endpoint of interest was trough forced expiratory volume in 1 second (FEV1) at 12 weeks. In order to minimize confounding bias, treatment by covariate interactions were incorporated in the models for baseline FEV1, current smokers (yes/no), and reversibility to short-acting β2-agonists (yes/no) and short-acting anticholinergics (yes/no).
RESULTS: The RCTs had similar study designs and inclusion criteria. Results with and without treatment*covariate interactions were consistent and the adjusted results are presented for FEV1 at 12 weeks. All interventions were more efficacious than placebo. Indacaterol 75μg resulted in a higher FEV1 compared to formoterol 12μg (70 mL difference; 95% Credible Interval [CrI] 20 to 110 mL). Indacaterol 75μg resulted in similar FEV1 improvements compared to tiotropium (0 mL; 95% CrI -50 to 40 mL) and salmeterol 50μg (20 mL; 95% CrI -30 to 70 mL).
CONCLUSIONS: The IPD network meta-analysis of six RCTs suggested that indacaterol 75μg OD is at least as efficacious as tiotropium OD 18μg open label and salmeterol BID 50μg and is expected to show a greater improvement than formoterol 12μg BID on trough FEV1.
CLINICAL IMPLICATIONS: Indirect evidence supports indacaterol 75μg as an alternative to existing long-acting β2-agonists and anticholinergics.
DISCLOSURE: Shannon Cope: Employee: Mapi Values, Boston, Ma. Study was funded by Novartis Pharmaceuticals
Jie Zhang: Employee: Novartis Pharmaceuticals
Swetha Raparla: Employee: Novartis Pharmaceuticals
James Williams: Employee: Novartis Pharmaceuticals
Jeroen Jansen: Employee: Mapi Values, Boston, Ma. Study was funded by Novartis Pharmaceuticals
Investigational drug. Submitted to the FDA for the indication of COPD. Action date July 2011.