Impact of ICS/LABA and LABA/LAMA FDCs on functional and clinical outcomes in COPD: A network meta-analysis

Inhaled 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.

A 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.

Data 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.

The 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.