Evaluating triple ICS/LABA/LAMA therapies for COPD patients: a network meta-analysis of ETHOS, KRONOS, IMPACT, and TRILOGY studies

In some studies comparing triple with dual combination therapies in COPD there might be a possible effect of inhaler bias resulting from different inhaler devices being used in comparator arms. The aim of this study was a quantitative synthesis by considering the studies that directly compared triple ICS/LABA/LAMA vs. either dual LABA/LAMA or ICS/LABA therapies administered at fixed-dose combination (FDC) via the same inhaler device.


A network meta-analysis was performed to assess the efficacy/safety impact of triple ICS/LABA/LAMA FDC compared with dual LABA/LAMA and ICS/LBA FDCs administered via the same inhaler device in COPD patients. The treatment ranking was reported via the surface under the cumulative ranking curve analysis (SUCRA).


Data obtained from 21,909 COPD patients were extracted from the ETHOS, KRONOS, IMPACT, and TRILOGY studies, the only that fulfilled the strict inclusion criteria of this research. The weighted efficacy/safety profile resulting from SUCRA provided the following ranking in patients with low eosinophil count: ICS/LABA/LAMA>LABA/LAMA≫ICS/LABA; whereas in patients with high eosinophil count the ranking was as follows: ICS/LABA/LAMA>LABA/LAMA>ICS/LABA FDC.


Triple ICS/LABA/LAMA FDC and dual LABA/LAMA or ICS/LABA FDCs are characterized by specific efficacy/safety profiles in agreement with the level of blood eosinophil count at baseline.