• Luigino Calzetta, Fabiano Di Marco, Francesco Blasi, Mario Cazzola, Stefano Centanni, Claudio Micheletto, Andrea Rossi, and Paola Rogliani.
• Department of Experimental Medicine and Surgery, University of Rome "Tor Vergata", Rome, Italy.
• Pulm Pharmacol Ther. 2019 Dec 1; 59: 101855.

BackgroundInhaled corticosteroid (ICS)/long-acting β2 agonist (LABA) fixed-dose combinations (FDCs) and LABA/long-acting muscarinic antagonist (LAMA) FDCs are extensively used to treat chronic obstructive pulmonary disease (COPD). The aim of the present network meta-analysis was to assess the comparative efficacy of all the currently available dual therapies in patients with moderate-to-severe COPD.MethodsA network meta-analysis (≥3 nodes, Bayesian method) was performed by searching for randomized clinical trials (RCTs) that compared the impact of different LABA/LAMA FDCs vs. ICS/LABA FDCs on both primary and secondary endpoints. The primary endpoints were: the change from baseline in trough forced expiratory volume in 1 s (FEV1) and the risk of exacerbation of COPD (AECOPD). The secondary endpoints were: peak FEV1, St' George's Respiratory Questionnaire (SGRQ), Transition Dyspnea Index (TDI), and rescue medication use.ResultsData of 17,734 COPD patients were extracted from 16 RCTs. The length of treatment ranged from 6 weeks to 52 weeks. All LABA/LAMA FDCs, except aclidinium/formoterol, produced a statistically significant improvement compared to ICS/LABAs in trough FEV1. The surface under the cumulative ranking curve (SUCRA) analysis indicated that umeclidinium/vilanterol, glycopyrronium/indacaterol and glycopyrrolate/formoterol fumarate were the most effective FDCs in improving trough FEV1. Across the FDCs analyzed for the risk of AECOPD, glycopyrronium/indacaterol significantly reduced the exacerbation risk compared to fluticasone propionate/salmeterol and resulted the most effective combination in the SUCRA analysis. Similar trend were also observed for the peak FEV1. No significant differences were detected across the investigated FDCs regarding SGRQ, TDI, and use of rescue medication.ConclusionsThe results of this meta-analysis show that LABA/LAMA combinations are consistently more effective than ICS/LABA FDCs for most of the evaluated outcomes. However, differences have also been observed between FDCs belonging to the same class. Across the investigated LABA/LAMA FDCs, glycopyrronium/indacaterol revealed a consistent and robust efficacy profile.Copyright © 2019 Elsevier Ltd. All rights reserved.

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